PAINWeek Journal Vol 5, Q1 by PAINWeek

vol. 5 q 1 2017

interdisciplinary management of pelvic pain: bridging the gap between primary care and specialty referral p.18 a gathering storm: are perioperative opioids problematic? p.26 developing a pain initiative under the current hcahps care survey p.34 catch 22: paradox = resolution p.46

p.39

TIME TO DUAL

TW O O NE SOURCES SOURCE

OF PAIN OF RELIEF NUCYNTA® ER is the first and only FDA-approved long-acting opioid designed to control both nociceptive pain and the neuropathic pain associated with diabetic peripheral neuropathy (DPN). Not an actual patient.

Visit Nucynta.com for more information and to download a NUCYNTA® ER savings card

INDICATIONS AND USAGE Limitations of Use NUCYNTA ER is an opioid agonist indicated for the management of: • Because of the risks of addiction, abuse, and misuse with opioids, • pain severe enough to require daily, around-the-clock, longeven at recommended doses, and because of the greater risks of term opioid treatment and for which alternative treatment overdose and death with extended-release opioid formulations, options are inadequate reserve NUCYNTA ER for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate• neuropathic pain associated with diabetic peripheral release opioids) are ineffective, not tolerated, or would be neuropathy (DPN) severe enough to require daily, around-theotherwise inadequate to provide sufficient management of pain. clock, long-term opioid treatment and for which alternative treatment options are inadequate. • NUCYNTA ER is not indicated as an as-needed (prn) analgesic. NUCYNTA® ER IMPORTANT SAFETY INFORMATION WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE- THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; INTERACTION WITH ALCOHOL and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS See full prescribing information for complete boxed warning. • NUCYNTA ER exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk before prescribing, and monitor regularly for development of these behaviors or conditions. (5.1) • Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely, especially upon initiation or following a dose increase. Instruct patients to swallow NUCYNTA ER tablets whole to avoid exposure to a potentially fatal dose of tapentadol. (5.2) • Accidental ingestion of NUCYNTA ER, especially in children, can result in fatal overdose of tapentadol. (5.2) • Prolonged use of NUCYNTA ER during pregnancy can result in neonatal opioid withdrawal syndrome, which may be lifethreatening if not recognized and treated. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available (5.3). • Instruct patients not to consume alcohol or any products containing alcohol while taking NUCYNTA ER because co-ingestion can result in fatal plasma tapentadol levels. (5.4) • Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation. (5.4), (7).

Please see additional Important Safety Information, including BOXED WARNING, and Brief Summary on the following pages.

NUCYNTA® ER (tapentadol) IMPORTANT SAFETY INFORMATION (continued) CONTRAINDICATIONS NUCYNTA ER is contraindicated in patients with: • Significant respiratory depression • Acute or severe bronchial asthma or hypercarbia in an unmonitored setting or in the absence of resuscitative equipment • Known or suspected gastrointestinal obstruction, including paralytic ileus • Hypersensitivity (e.g. anaphylaxis, angioedema) to tapentadol or to any other ingredients of the product. • Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days WARNINGS AND PRECAUTIONS Addiction, Abuse, and Misuse NUCYNTA ER contains tapentadol, a Schedule II controlled substance. As an opioid, NUCYNTA ER exposes users to the risks of addiction, abuse, and misuse. Because extendedrelease products such as NUCYNTA ER deliver the opioid over an extended period of time, there is a greater risk for overdose and death due to the larger amount of tapentadol present. Addiction can occur at recommended doses and if the drug is misused or abused. Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing NUCYNTA ER, and monitor all patients receiving NUCYNTA ER for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). Abuse or misuse of NUCYNTA ER by crushing, chewing, snorting, or injecting the dissolved product will result in the uncontrolled delivery of tapentadol and can result in overdose and death. Opioid are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing NUCYNTA ER. Life-threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. To reduce the risk of respiratory depression, proper dosing and titration of NUCYNTA ER are essential. Overestimating the NUCYNTA ER dosage when converting patients from another opioid product can result in fatal overdose with the first dose. Accidental ingestion of even one dose of NUCYNTA ER, especially by children, can result in respiratory depression and death due to an overdose of tapentadol. Neonatal Opioid Withdrawal Syndrome Prolonged use of NUCYNTA ER during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal

opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. Risk from Concomitant Use with Benzodiazepines or Other CNS Depressants Patients must not consume alcoholic beverages or prescription or non-prescription products containing alcohol while on NUCYNTA ER therapy. The co-ingestion of alcohol with NUCYNTA ER may result in increased plasma tapentadol levels and a potentially fatal overdose of tapentadol. Profound sedation, respiratory depression, coma, and death may result from the concomitant use of NUCYNTA ER with benzodiazepines or other CNS depressants (e.g., nonbenzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Follow patients closely for signs and symptoms of respiratory depression and sedation. Advise both patients and caregivers about the risks of respiratory depression and sedation when NUCYNTA ER is used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs). Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined. Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs. Risk of Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients The use of NUCYNTA ER in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated. Patients with Chronic Pulmonary Disease: NUCYNTA ER treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of NUCYNTA ER.

NUCYNTAÂŽ ER (tapentadol) IMPORTANT SAFETY INFORMATION (continued) Elderly, Cachectic, or Debilitated Patients: Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients. Alternatively, consider the use of non-opioid analgesics in these patients. Serotonin Syndrome with Concomitant Use of Serotonergic Drugs Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of tapentadol with serotonergic drugs.Serotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonergic neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), and drugs that impair metabolism of serotonin (including MAO inhibitors, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). This may occur within the recommended dosage range. See Warnings and Precautions in full Prescribing Information for a list of symptoms associated with Serotonin Syndrome. Discontinue NUCYNTA ER if serotonin syndrome is suspected. Adrenal Insufficiency Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency. Severe Hypotension NUCYNTA ER may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is an increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics). Monitor these patients for signs of hypotension after initiating or titrating the dosage of NUCYNTA ER. In patients with circulatory shock, NUCYNTA ER may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of NUCYNTA ER in patients with circulatory shock. Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness In patients who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), NUCYNTA ER may reduce respiratory

drive, and the resultant CO2 retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with NUCYNTA ER. Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of NUCYNTA ER in patients with impaired consciousness or coma. Risks of Use in Patients with Gastrointestinal Conditions NUCYNTA ER is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus. The tapentadol in NUCYNTA ER may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms. Increased Risk of Seizures in Patients with Seizure Disorders The tapentadol in NUCYNTA ER may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during NUCYNTA ER therapy. Withdrawal Avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who have received or are receiving a course of therapy with a full opioid agonist analgesic, including NUCYNTA ER. In these patients, mixed agonists/ antagonists and partial agonist analgesics may reduce the analgesic effect and/or may precipitate withdrawal symptoms. When discontinuing NUCYNTA ER, gradually taper the dose. Do not abruptly discontinue NUCYNTA ER. Risks of Driving and Operating Machinery NUCYNTA ER may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of NUCYNTA ER and know how they will react to the medication. Risk of Toxicity in Patients with Hepatic Impairment A study with an immediate-release formulation of tapentadol in subjects with hepatic impairment showed higher serum concentrations of tapentadol than in those with normal hepatic function. Avoid use of NUCYNTA ER in patients with severe hepatic impairment. Reduce the dose of NUCYNTA ER in patients with moderate hepatic impairment. Closely monitor patients with moderate hepatic impairment for respiratory and central nervous system depression when initiating and titrating NUCYNTA ER. Risk of Toxicity in Patients with Renal Impairment Use of NUCYNTA ER in patients with severe renal impairment is not recommended due to accumulation of a metabolite formed by glucuronidation of tapentadol. The clinical relevance of the elevated metabolite is not known. ADVERSE REACTIONS In clinical studies, the most common (â&#x2030;Ľ10%) adverse reactions were nausea, constipation, vomiting, dizziness, somnolence, and headache.

NUCYNTAÂŽ ER (tapentadol) IMPORTANT SAFETY INFORMATION (continued) Select Postmarketing Adverse Reactions Anaphylaxis, angioedema, and anaphylactic shock have been reported very rarely with ingredients contained in NUCYNTA ER. Advise patients how to recognize such reactions and when to seek medical attention. Panic attack has also been reported. DRUG INTERACTIONS Alcohol See BOXED WARNING. Benzodiazepines and Other Central Nervous System (CNS) Depressants See BOXED WARNING. Serotonergic Drugs See Warnings and Precautions. Monoamine Oxidase Inhibitors (MAOIs) See Contraindications. Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics May reduce the analgesic effect of NUCYNTA ER and/or precipitate withdrawal symptoms. Avoid concomitant use. Muscle Relaxants See BOXED WARNING and Warnings and Precautions. Diuretics Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed. Anticholinergic Drugs The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Monitor patients for signs of urinary retention or reduced gastric motility when NUCYNTA ER is used concomitantly with anticholinergic drugs. USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Category C. NUCYNTA ER should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome. Labor or Delivery Opioids cross the placenta and may produce respiratory depression in neonates. NUCYNTA ER is not recommended for use in pregnant women during and immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate. Opioid analgesics, including NUCYNTA ER, can prolong labor through actions that temporarily reduce the strength, duration, and frequency of uterine contractions. Lactation Because of the potential for serious adverse reactions including excess sedation and respiratory depression in a breastfed infant, advise patients that breast feeding is not recommended during treatment with NUCYNTA ER.

Females and Males of Reproductive Potential Infertility Chronic use of opioids may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible. Pediatric Use The safety and efficacy of NUCYNTA ER in pediatric patients less than 18 years of age have not been established. Geriatric Use Elderly patients (aged 65 or older) may have increased sensitivity to tapentadol. In general, use caution when selecting a dosage for an elderly patient. Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of NUCYNTA ER slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression. Hepatic Impairment Use of NUCYNTA ER in patients with severe hepatic impairment is not recommended. In patients with moderate hepatic impairment, dosage reduction of NUCYNTA ER is recommended. Renal Impairment Use of NUCYNTA ER in patients with severe renal impairment is not recommended. DRUG ABUSE AND DEPENDENCE See BOXED WARNING OVERDOSAGE In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen, vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life support techniques. Please see Brief Summary, including BOXED WARNING, on the following pages.

BRIEF SUMMARY OF FULL PRESCRIBING INFORMATION This does not include all the information needed to use NUCYNTA® ER safely and effectively. See full Prescribing Information for NUCYNTA® ER. INDICATIONS AND USAGE NUCYNTA® ER is indicated for the management of: • pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate • neuropathic pain associated with diabetic peripheral neuropathy (DPN) in adults severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. Limitations of Usage • Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve NUCYNTA® ER for use in patients for whom alternative treatment options (e.g., nonopioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. • NUCYNTA® ER is not indicated as an as-needed (prn) analgesic. WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; AND INTERACTION WITH ALCOHOL See full prescribing information for complete boxed warning. • NUCYNTA® ER exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk before prescribing, and monitor regularly for development of these behaviors or conditions. (5.1) • Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely, especially upon initiation or following a dose increase. Instruct patients to swallow NUCYNTA® ER tablets whole to avoid exposure to a potentially fatal dose of tapentadol. (5.2) • Accidental ingestion of NUCYNTA® ER, especially in children, can result in fatal overdose of tapentadol. (5.2) • Prolonged use of NUCYNTA® ER during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. (5.3) • Instruct patients not to consume alcohol or any products containing alcohol while taking NUCYNTA® ER because co-ingestion can result in fatal plasma tapentadol levels. (5.4) CONTRAINDICATIONS Significant respiratory depression; acute or severe bronchial asthma or hypercarbia in an unmonitored setting or in the absence of resuscitative equipment; known or suspected paralytic ileus; hypersensitivity (e.g., anaphylaxis, angioedema) to tapentadol or to any other ingredients of the product; concurrent use of monoamine oxidase inhibitors (MAOIs) or use within the last 14 days. WARNINGS AND PRECAUTIONS Addiction, Abuse, and Misuse: NUCYNTA® ER contains tapentadol, a Schedule II controlled substance. As an opioid, NUCYNTA® ER exposes users to the risks of addiction, abuse, and misuse. As modified-release products such as NUCYNTA® ER deliver the opioid over an extended period of time, there is a greater risk for overdose and death due to the larger amount of tapentadol present. Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed NUCYNTA® ER and in those who obtain the drug illicitly. Addiction can occur at recommended doses and if the drug is misused or abused. Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing NUCYNTA® ER, and monitor all patients receiving NUCYNTA® ER for the development of these behaviors or conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol addiction or abuse) or mental illness (e.g., major depression).The potential for these risks should not, however, prevent the prescribing of NUCYNTA® ER for the proper management of pain in any given patient. Patients at increased risk may be prescribed modified-release opioid formulations such as NUCYNTA® ER, but use in such patients necessitates intensive counseling about the risks and proper use of NUCYNTA® ER along with intensive monitoring for signs of addiction, abuse, and misuse. Abuse or misuse of NUCYNTA® ER by crushing, chewing, snorting, or injecting the dissolved product will result in the uncontrolled delivery of tapentadol and can result in overdose and death. Opioid agonists such as NUCYNTA® ER are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing NUCYNTA® ER. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug. Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product. Life-Threatening Respiratory Depression: Serious, life-threatening, or fatal respiratory depression has been reported with the use of modified release opioids, even when used as recommended. Respiratory depression from opioid use, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status. Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of NUCYNTA® ER, the risk is greatest during the initiation of therapy or following a dose increase. Closely monitor patients for respiratory depression when initiating therapy with NUCYNTA® ER and following dose increases. To reduce the risk of respiratory depression, proper dosing and titration of NUCYNTA® ER are essential. Overestimating the NUCYNTA® ER dose when converting patients from another opioid product can result in fatal overdose with the first dose. Accidental ingestion of even one dose of NUCYNTA® ER, especially by children, can result in respiratory depression and death due to an overdose of tapentadol.

Neonatal Opioid Withdrawal Syndrome: Prolonged use of NUCYNTA® ER during pregnancy can result in withdrawal signs in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Interactions with Central Nervous System Depressants: Patients must not consume alcoholic beverages or prescription or non-prescription products containing alcohol while on NUCYNTA® ER therapy. The co-ingestion of alcohol with NUCYNTA® ER may result in increased plasma tapentadol levels and a potentially fatal overdose of tapentadol. Hypotension, profound sedation, coma, respiratory depression, and death may result if NUCYNTA® ER is used concomitantly with alcohol or other central nervous system (CNS) depressants (e.g., sedatives, anxiolytics, hypnotics, neuroleptics, other opioids). When considering the use of NUCYNTA® ER in a patient taking a CNS depressant, assess the duration of use of the CNS depressant and the patient’s response, including the degree of tolerance that has developed to CNS depression. Additionally, evaluate the patient’s use of alcohol or illicit drugs that cause CNS depression. If the decision to begin NUCYNTA® ER is made, start with NUCYNTA® ER 50 mg every 12 hours, monitor patients for signs of sedation and respiratory depression, and consider using a lower dose of the concomitant CNS depressant. Use in Elderly, Cachectic, and Debilitated Patients: Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients. Therefore, closely monitor such patients, particularly when initiating and titrating NUCYNTA® ER and when NUCYNTA® ER is given concomitantly with other drugs that depress respiration. Use in Patients with Chronic Pulmonary Disease: Monitor for respiratory depression those patients with significant chronic obstructive pulmonary disease or cor pulmonale, and patients having a substantially decreased respiratory reserve, hypoxia, hypercarbia, or pre-existing respiratory depression, particularly when initiating therapy and titrating with NUCYNTA® ER, as in these patients, even usual therapeutic doses of NUCYNTA® ER may decrease respiratory drive to the point of apnea. Consider the use of alternative non-opioid analgesics in these patients if possible. Hypotensive Effect: NUCYNTA® ER may cause severe hypotension. There is an increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics). Monitor these patients for signs of hypotension after initiating or titrating the dose of NUCYNTA® ER. In patients with circulatory shock, NUCYNTA® ER may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of NUCYNTA® ER in patients with circulatory shock. Use in Patients with Head Injury or Increased Intracranial Pressure: Monitor patients taking NUCYNTA® ER who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors) for signs of sedation and respiratory depression, particularly when initiating therapy with NUCYNTA® ER. NUCYNTA® ER may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Opioids may also obscure the clinical course in a patient with ahead injury. Avoid the use of NUCYNTA® ER in patients with impaired consciousness or coma. Seizures: NUCYNTA® ER has not been evaluated in patients with a predisposition to a seizure disorder, and such patients were excluded from clinical studies. The active ingredient tapentadol in NUCYNTA® ER may aggravate convulsions in patients with convulsive disorders, and may induce or aggravate seizures in some clinical settings. Monitor patients with a history of seizure disorders for worsened seizure control during NUCYNTA® ER therapy. Serotonin Syndrome: Cases of life-threatening serotonin syndrome have been reported with the concurrent use of tapentadol and serotonergic drugs. Serotonergic drugs comprise Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, drugs that affect the serotonergic neurotransmitter system (e.g. mirtazapine, trazodone, and tramadol), and drugs that impair metabolism of serotonin (including MAOIs). This may occur within the recommended dose. Serotonin syndrome may include mental-status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea) and can be fatal. Use in Patients with Gastrointestinal Conditions: NUCYNTA® ER is contraindicated in patients with GI obstruction, including paralytic ileus. The tapentadol in NUCYNTA® ER may cause spasm of the sphincter of Oddi. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms. Avoidance of Withdrawal: Avoid the use of mixed agonist/antagonist (i.e., pentazocine, nalbuphine, and butorphanol) or partial agonist (buprenorphine) analgesics in patients who have received or are receiving a course of therapy with a full opioid agonist analgesic, including NUCYNTA® ER. In these patients, mixed agonists/antagonists and partial agonist analgesics may reduce the analgesic effect and/or may precipitate withdrawal symptoms. When discontinuing NUCYNTA® ER, gradually taper the dose. Driving and Operating Heavy Machinery: NUCYNTA® ER may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of NUCYNTA® ER and know how they will react to the medication. Hepatic Impairment: A study with an immediate-release formulation of tapentadol in subjects with hepatic impairment showed higher serum concentrations of tapentadol than in those with normal hepatic function. Avoid use of NUCYNTA® ER in patients with severe hepatic impairment. Reduce the dose of NUCYNTA® ER in patients with moderate hepatic impairment. Closely monitor patients with moderate hepatic impairment for respiratory and central nervous system depression when initiating and titrating NUCYNTA® ER. Renal Impairment: Use of NUCYNTA® ER in patients with severe renal impairment is not recommended due to accumulation of a metabolite formed by glucuronidation of tapentadol. The clinical relevance of the elevated metabolite is not known.

ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: • Addiction, Abuse, and Misuse [see Warnings and Precautions (5.1)] • Life-Threatening Respiratory Depression [see Warnings and Precautions (5.2)] • Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.3)] • Interaction with Other CNS Depressants [see Warnings and Precautions (5.4)] • Hypotensive Effects [see Warnings and Precautions (5.7)] • Gastrointestinal Effects [see Warnings and Precautions (5.11)] • Seizures [see Warnings and Precautions (5.9)] • Serotonin Syndrome [see Warnings and Precautions (5.10)] Clinical Trial Experience Commonly-Observed Adverse Reactions in Clinical Studies with NUCYNTA® ER in Patients with Chronic Pain due to Low Back Pain or Osteoarthritis The most common adverse reactions (reported by ≥10% in any NUCYNTA® ER dose group) were: nausea, constipation, dizziness, headache, and somnolence. The most common reasons for discontinuation due to adverse reactions in eight Phase 2/3 pooled studies reported by ≥1% in any NUCYNTA® ER dose group for NUCYNTA® ER- and placebo-treated patients were nausea (4% vs. 1%), dizziness (3% vs. <1%), vomiting (3% vs. <1%), somnolence (2% vs. <1%), constipation (1% vs. <1%), headache (1% vs. <1%), and fatigue (1% vs. <1%), respectively. Commonly-Observed Adverse Reactions in Clinical Studies with NUCYNTA® ER in Patients with Neuropathic Pain Associated with Diabetic Peripheral Neuropathy The most commonly reported ADRs (incidence ≥ 10% in NUCYNTA® ER-treated subjects) were: nausea, constipation, vomiting, dizziness, somnolence, and headache. Postmarketing Experience: The following adverse reactions, not above, have been identified during post approval use of tapentadol. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Psychiatric disorders: hallucination, suicidal ideation, panic attack. Anaphylaxis, angioedema, and anaphylactic shock have been reported very rarely with ingredients contained in NUCYNTA® ER. Advise patients how to recognize such reactions and when to seek medical attention. DRUG INTERACTIONS Alcohol: Concomitant use of alcohol with NUCYNTA® ER can result in an increase of tapentadol plasma levels and potentially fatal overdose of tapentadol. Instruct patients not to consume alcoholic beverages or use prescription or non-prescription products containing alcohol while on NUCYNTA® ER therapy. Monoamine Oxidase Inhibitors: NUCYNTA® ER is contraindicated in patients who are receiving monoamine oxidase inhibitors (MAOIs) or who have taken them within the last 14 days due to potential additive effects on norepinephrine levels, which may result in adverse cardiovascular events. CNS Depressants: The concomitant use of NUCYNTA® ER with other CNS depressants including sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other opioids, and alcohol can increase the risk of respiratory depression, profound sedation, coma and death. Monitor patients receiving CNS depressants and NUCYNTA® ER for signs of respiratory depression, sedation and hypotension. When combined therapy with any of the above medications is considered, the dose of one or both agents should be reduced. Serotonergic Drugs: There have been post-marketing reports of serotonin syndrome with the concomitant use of tapentadol and serotonergic drugs (e.g., SSRIs and SNRIs). Caution is advised when NUCYNTA® ER is coadministered with other drugs that may affect serotonergic neurotransmitter systems such as SSRIs, SNRIs, MAOIs, and triptans. If concomitant treatment of NUCYNTA® ER with a drug affecting the serotonergic neurotransmitter system is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases. Muscle Relaxants: Tapentadol may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. Monitor patients receiving muscle relaxants and NUCYNTA® ER for signs of respiratory depression that may be greater than otherwise expected. Mixed Agonist/Antagonist Opioid Analgesics: Mixed agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, and butorphanol) and partial agonists (e.g., buprenorphine) may reduce the analgesic effect of NUCYNTA® ER or precipitate withdrawal symptoms. Avoid the use of mixed agonist/ antagonist analgesics in patients receiving NUCYNTA® ER. Anticholinergics: The use of NUCYNTA® ER with anticholinergic products may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. USE IN SPECIFIC POPULATIONS Pregnancy Clinical Considerations Fetal/neonatal adverse reactions Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Observe newborns for symptoms of neonatal opioid withdrawal syndrome, such as poor feeding, diarrhea, irritability, tremor, rigidity, and seizures, and manage accordingly. Teratogenic Effects - Pregnancy Category C There are no adequate and well-controlled studies in pregnant women. NUCYNTA® ER should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Labor and Delivery: Opioids cross the placenta and may produce respiratory depression in neonates. NUCYNTA® ER is not for use in women during and immediately prior to labor, when shorter acting analgesics or other analgesic techniques are more appropriate. Opioid analgesics can prolong labor through actions that temporarily reduce the strength, duration, and frequency of uterine contractions. However this effect is not consistent and may be offset by an increased rate of cervical dilatation, which tends to shorten labor. Nursing Mothers: There is insufficient/limited information on the excretion of tapentadol in human or animal breast milk. Physicochemical and available pharmacodynamic/toxicological data on tapentadol point to excretion in breast milk and risk to the breastfeeding child cannot be excluded. Because of the potential for adverse reactions in nursing infants from NUCYNTA® ER, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. Withdrawal symptoms can occur in breast-feeding infants when maternal administration of

NUCYNTA® ER is stopped. Pediatric Use: The safety and efficacy of NUCYNTA® ER in pediatric patients less than 18 years of age have not been established. Geriatric Use: Of the total number of patients in Phase 2/3 double-blind, multiple-dose clinical studies of NUCYNTA® ER, 28% (1023/3613) were 65 years and over, while 7% (245/3613) were 75 years and over. No overall differences in effectiveness or tolerability were observed between these patients and younger patients. In general, recommended dosing for elderly patients with normal renal and hepatic function is the same as for younger adult patients with normal renal and hepatic function. Because elderly patients are more likely to have decreased renal and hepatic function, consideration should be given to starting elderly patients with the lower range of recommended doses. Renal Impairment: The safety and effectiveness of NUCYNTA® ER have not been established in patients with severe renal impairment (CLCR <30 mL/min). Use of NUCYNTA® ER in patients with severe renal impairment is not recommended due to accumulation of a metabolite formed by glucuronidation of tapentadol. The clinical relevance of the elevated metabolite is not known. Hepatic Impairment: Administration of tapentadol resulted in higher exposures and serum levels of tapentadol in subjects with impaired hepatic function compared to subjects with normal hepatic function. The dose of NUCYNTA® ER should be reduced in patients with moderate hepatic impairment (Child-Pugh Score 7 to 9). Use of NUCYNTA® ER is not recommended in severe hepatic impairment (Child-Pugh Score 10 to 15). DRUG ABUSE AND DEPENDENCE Controlled Substance: NUCYNTA® ER contains tapentadol, a Schedule II controlled substance with a high potential for abuse similar to fentanyl, methadone, morphine, oxycodone, and oxymorphone. NUCYNTA® ER can be abused and is subject to misuse, addiction, and criminal diversion. The high drug content in the extended release formulation adds to the risk of adverse outcomes from abuse and misuse. Abuse: All patients treated with opioids require careful monitoring for signs of abuse and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. Drug abuse is the intentional non-therapeutic use of an over-the-counter or prescription drug, even once, for its rewarding psychological or physiological effects. Drug abuse includes, but is not limited to the following examples: the use of a prescription or over-the-counter drug to get “high,” or the use of steroids for performance enhancement and muscle build up. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and include: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal. “Drug-seeking” behavior is very common to addicts and drug abusers. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing or referral, repeated claims of loss of prescriptions, tampering with prescriptions and reluctance to provide prior medical records or contact information for other treating physician(s). “Doctor shopping” (visiting multiple prescribers) to obtain additional prescriptions is common among drug abusers, and people suffering from untreated addiction. Preoccupation with achieving pain relief can be appropriate behavior in a patient with poor pain control. Abuse and addiction are separate and distinct from physical dependence and tolerance. Physicians should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction. NUCYNTA® ER, like other opioids, can be diverted for non-medical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by law, is strongly advised. Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. Dependence: Both tolerance and physical dependence can develop during chronic opioid therapy. Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects. Physical dependence results in withdrawal symptoms after abrupt discontinuation or a significant dose reduction of a drug. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity, e.g., naloxone, nalmefene, mixed agonist/antagonist analgesics (pentazocine, butorphanol, nalbuphine), or partial agonists (buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage. NUCYNTA® ER should not be abruptly discontinued. If NUCYNTA® ER is abruptly discontinued in a physically-dependent patient, an abstinence syndrome may occur. Some or all of the following can characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, piloerection, myalgia, mydriasis, irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, increased blood pressure, respiratory rate, or heart rate. Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal symptoms. OVERDOSAGE Clinical Presentation: Acute overdosage with opioids can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and sometimes pulmonary edema, bradycardia, hypotension and death. Marked mydriasis rather than miosis may be seen due to severe hypoxia in overdose situations. Treatment of Overdose: In case of overdose, priorities are the re-establishment of a patent and protected airway and institution of assisted or controlled ventilation if needed. Employ other supportive measures (including oxygen, vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life support techniques. Rx Only

eXeCUTiVe eDiTOR KEViN L. ZACHAROFF md, facpe, facip, faap

eeK

PUBLiSHeR PAINW

ART DiReCTOR DARRYL FOSSA

eDiTORiAL DiReCTOR DeBRA WeiNeR eDiTOR HOLLY CASTeR

Charles E. Argoff md, cpe Professor of Neurology Albany Medical College Department of Neurology Director Comprehensive Pain Center Albany Medical Center Department of Neurology Albany, ny Paul Arnstein rn, phd, acns-bc, fnp-c, faan Clinical Nurse Specialist for Pain Relief Massachusetts General Hospital Boston, ma Said R. Beydoun md, faan Professor of Neurology Director of the Neuromuscular Program Keck Medical Center of University of Southern California Los Angeles, ca Jennifer Bolen jd Founder Legal Side of Pain Knoxville, tn Paul J. Christo md, mba Associate Professor Johns Hopkins University School of Medicine Department of Anesthesiology and Critical Care Medicine Baltimore, md Michael R. Clark MD mph, mba Vice Chair, Clinical Affairs Johns Hopkins University School of Medicine Department of Psychiatry and Behavioral Sciences Director, Pain Treatment Programs Johns Hopkins Medical Institutions Department of Psychiatry and Behavioral Sciences Baltimore, md Geralyn Datz phd Affiliate University of Southern Mississippi Department of Psychology Clinical Director Southern Behavioral Medicine Associates Hattiesburg, ms

eDiTORiAL BOARD

Peter A. Foreman dds, daapm Consultant Rotorua Hospital and Private Practice Rotorua, New Zealand Gary W. Jay md, faapm, facfei Clinical Professor Department of Neurology Division: Headache University of North Carolina Chapel Hill, nc Mary Lynn McPherson pharmd, bcps, cpe, faspe Professor and Vice Chair University of Maryland School of Pharmacy Department of Pharmacy Practice and Science Hospice Consultant Pharmacist Baltimore, md Srinivas Nalamachu md Clinical Assistant Professor Kansas University Medical Center Department of Rehabilitation Medicine Kansas City, ks President and Medical Director International Clinical Research Institute Overland Park, ks Bruce D. Nicholson md Clinical Associate Professor Department of Anesthesia Penn State College of Medicine Hershey Medical Center Hershey, pa Director of Pain Specialists Lehigh Valley Health Network Department of Anesthesiology Allentown, pa

Marco Pappagallo md Director of Medical Intelligence Grünenthal usa Bedminster, nj Director Pain Management & Medical Mentoring New Medical Home for Chronic Pain New York, ny Steven D. Passik phd Vice President Scientific Affairs, Policy, and Education Collegium Pharmaceuticals, Inc. Canton, ma Joseph V. Pergolizzi md Adjunct Assistant Professor Johns Hopkins University School of Medicine Department of Medicine Baltimore, md Senior Partner Naples Anesthesia and Pain Medicine Naples, fl Robert W. Rothrock pa-c, mpa University of Pennsylvania Department of Anesthesiology and Critical Care Pain Medicine Division Philadelphia, pa Michael E. Schatman phd, cpe, daspe Editor-in-Chief Journal of Pain Research Adjunct Clinical Assistant Professor Tufts University School of Medicine Department of Health & Community Medicine Boston, ma Sanford M. Silverman md CEO and Medical Director Comprehensive Pain Medicine Pompano Beach, fl Thomas B. Strouse md Medical Director Stewart and Lynda Resnick Neuropsychiatric Hospital at ucla Los Angeles, ca

Copyright © 2017, PAINWeek, a division of Tarsus Medical Group. The opinions stated in the enclosed printed materials are those of the authors and do not necessarily represent the opinions of PAINWeek or its publication staff. PAINWeek does not give guarantees or any other representation that the printed material contained herein is valid, reliable, or accurate. PAINWeek does not assume any responsibility for injury arising from any use or misuse of the printed materials contained herein. The printed materials contained herein are assumed to be from reliable sources, and there is no implication that they represent the only, or best, methodologies or procedures for the pain condition discussed. It is incumbent upon the reader to verify the accuracy of any diagnosis and drug dosage information contained herein, and to make modifications as new information arises. All rights are reserved by PAINWeek to accept, reject, or modify any advertisement submitted for publication. It is the policy of PAINWeek to not endorse products. Any advertising herein may not be construed as an endorsement, either expressed or implied, of a product or service.

Global Education Group (Global) is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education to physicians. Global Education Group designates this live activity for a minimum of 36.0 AMA PRA Category 1 Credit(s)TM. This activity will be approved for continuing pharmacy, psychology, nurse practitioner, nursing, and dentistry education. Applications for certification of social work NASW and family physician AAFP hours will be applied for. For more information and complete CME/CE accreditation details, visit our website at www.painweek.org.

vol. 5 q 1 2017

18 26 34 46 53 54 55 56 58

women's health

interdisciplinary management of pelvic pain: bridging the gap between primary care and specialty referral

by jennifer hah ravi prasad

pharmacotherapy

a gathering storm: are perioperative opioids problematic

by michael bonnette ikram malik michael bottros

key topics

developing a pain initiative under the current hcahps care survey

by jeffrey a. gudin

clinical conundrum

catch-22: paradox=resolution

by gary w. jay

pw next generation

with david cosio

clinical pearls

by douglas gourlay

pain by numbers one-minute clinician

with sean fargo, charles argoff, jeremy adler, sondra m. adkinson, dawn buse

pundit profile

with sanford m. silverman

P. 39

PWJ | www.painweek.org

Q1 | 2017

Oral Formulation A treatment for opioid-induced constipation (OIC) for your adult patients with chronic non-cancer pain (CNCP) that may help them

GO LIKE CLOCKWORK RELISTOR Tablets: The OIC treatment you trust, available in an oral formulation with once-daily dosing. By delivering a reliable, rapid response, RELISTOR tablets may give your adult patients the relief from OIC they can count on. In a clinical study, 52% of patients receiving RELISTOR tablets* had at least 3 spontaneous bowel movements† per week over 4 weeks vs 38% of patients receiving placebo (P=.005).1,2

Tablets

* Three 150-mg tablets (450 mg total) once daily in the morning with water on an empty stomach at least 30 minutes before the first meal of the day.1 † Defined as bowel movement without the use of any laxative in previous 24 hours.1

INDICATIONS • RELISTOR is an opioid antagonist. RELISTOR tablets and RELISTOR injection are indicated for the treatment of opioid-induced constipation (OIC) in adults with chronic non-cancer pain. • RELISTOR injection is also indicated for the treatment of OIC in adults with advanced illness who are receiving palliative care, when response to laxative therapy has not been sufficient. Limitations of Use: Use beyond four months has not been studied in the advanced illness population. IMPORTANT SAFETY INFORMATION - RELISTOR (methylnaltrexone bromide) tablets, for oral use and RELISTOR (methylnaltrexone bromide) injection, for subcutaneous use • RELISTOR tablets and injection are contraindicated in patients with known or suspected gastrointestinal obstruction and patients at increased risk of recurrent obstruction, due to the potential for gastrointestinal perforation. • Cases of gastrointestinal perforation have been reported in adult patients with opioid-induced constipation and advanced illness with conditions that may be associated with localized or diffuse reduction of structural integrity in the wall of the gastrointestinal tract (e.g., peptic ulcer disease, Ogilvie’s syndrome, diverticular disease, infiltrative gastrointestinal tract malignancies or peritoneal metastases). Take into account the overall risk-benefit profile when using RELISTOR in patients with these conditions or other conditions which might result in impaired integrity of the gastrointestinal tract wall (e.g., Crohn’s disease). Monitor for the development of severe, persistent, or worsening abdominal pain; discontinue RELISTOR in patients who develop this symptom. • If severe or persistent diarrhea occurs during treatment, advise patients to discontinue therapy with RELISTOR and consult their healthcare provider. • Symptoms consistent with opioid withdrawal, including hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, and yawning have occurred in patients treated with RELISTOR. Patients having disruptions to the blood-brain barrier may be at increased risk for opioid withdrawal and/or reduced analgesia and should be monitored for adequacy of analgesia and symptoms of opioid withdrawal. • Avoid concomitant use of RELISTOR with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal. Relistor is a trademark of Salix Pharmaceuticals or its affiliates. All rights reserved. RELO.0071.USA.16 November 2016 Printed in USA.

• The use of RELISTOR during pregnancy may precipitate opioid withdrawal in a fetus due to the immature fetal blood brain barrier and should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Because of the potential for serious adverse reactions, including opioid withdrawal, in breastfed infants, advise women that breastfeeding is not recommended during treatment with RELISTOR. In nursing mothers, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. • A dosage reduction of RELISTOR tablets and RELISTOR injection is recommended in patients with moderate and severe renal impairment (creatinine clearance less than 60 mL/minute as estimated by Cockcroft-Gault). No dosage adjustment of RELISTOR tablets or RELISTOR injection is needed in patients with mild renal impairment. • A dosage reduction of RELISTOR tablets is recommended in patients with moderate (Child-Pugh Class B) or severe (Child-Pugh Class C) hepatic impairment. No dosage adjustment of RELISTOR tablets is needed in patients with mild hepatic impairment (Child-Pugh Class A). No dosage adjustment of RELISTOR injection is needed for patients with mild or moderate hepatic impairment. In patients with severe hepatic impairment, monitor for methylnaltrexone-related adverse reactions. • In the clinical studies, the most common adverse reactions were: OIC in adult patients with chronic non-cancer pain • RELISTOR tablets (≥ 2% of RELISTOR patients and at a greater incidence than placebo): abdominal pain (14%), diarrhea (5%), headache (4%), abdominal distention (4%), vomiting (3%), hyperhidrosis (3%), anxiety (2%), muscle spasms (2%), rhinorrhea (2%), and chills (2%). • RELISTOR injection (≥ 1% of RELISTOR patients and at a greater incidence than placebo): abdominal pain (21%), nausea (9%), diarrhea (6%), hyperhidrosis (6%), hot flush (3%), tremor (1%), and chills (1%). OIC in adult patients with advanced illness • RELISTOR injection (≥ 5% of RELISTOR patients and at a greater incidence than placebo): abdominal pain (29%) flatulence (13%), nausea (12%), dizziness (7%), and diarrhea (6%).

Please see Brief Summary for RELISTOR tablets and RELISTOR injection on adjacent page and full Prescribing Information at relistor.com. REFERENCES: 1. RELISTOR [prescribing information]. Bridgewater, NJ: Salix Pharmaceuticals; 2016. 2. Data on file, Salix Pharmaceuticals.

The safety of RELISTOR injection was evaluated in a double-blind, placebocontrolled trial in adult patients with OIC and chronic non-cancer pain receiving opioid analgesia. This study (Study 2) included a 4-week, doubleblind, placebo-controlled period in which adult patients were randomized to receive RELISTOR injection 12 mg subcutaneously once daily (150 patients) or placebo (162 patients). After 4 weeks of double-blind treatment, patients began an 8-week open-label treatment period during which RELISTOR injection 12 mg subcutaneously was administered less frequently than the recommended dosage regimen of 12 mg once daily. The most common adverse reactions in adult patients with OIC and chronic non-cancer pain receiving RELISTOR injection are shown in Table 5. The adverse reactions in the table below may reflect symptoms of opioid withdrawal.

BRIEF SUMMARY OF PRESCRIBING INFORMATION This Brief Summary does not include all the information needed to use RELISTOR safely and effectively. See full prescribing information for RELISTOR. RELISTOR (methylnaltrexone bromide) 150 mg tablets, for oral use. RELISTOR (methylnaltrexone bromide) injection, for subcutaneous use. 8 mg/0.4 mL methylnaltrexone bromide in single-dose pre-filled syringe. 12 mg/0.6 mL methylnaltrexone bromide in a single-dose pre-filled syringe, or single-dose vial. Initial U.S. Approval: 2008 INDICATIONS AND USAGE RELISTOR is an opioid antagonist. RELISTOR tablets and RELISTOR injection are indicated for the treatment of opioid-induced constipation (OIC) in adults with chronic non-cancer pain. RELISTOR injection is also indicated for the treatment of OIC in adults with advanced illness who are receiving palliative care, when response to laxative therapy has not been sufficient. Limitations of Use: Use beyond four months has not been studied in the advanced illness population. CONTRAINDICATIONS RELISTOR tablets and injection are contraindicated in patients with known or suspected mechanical gastrointestinal obstruction and patients at increased risk of recurrent obstruction, due to the potential for gastrointestinal perforation. WARNINGS AND PRECAUTIONS Gastrointestinal Perforation Consider the overall risk benefit in patients with known or suspected lesions of the GI tract. Cases of gastrointestinal perforation have been reported in adult patients with OIC and advanced illness with conditions that may be associated with localized or diffuse reduction of structural integrity in the wall of the gastrointestinal tract (e.g., peptic ulcer disease, Ogilvie’s syndrome, diverticular disease, infiltrative gastrointestinal tract malignancies or peritoneal metastases). Take into account the overall risk-benefit profile when using RELISTOR in patients with these conditions or other conditions which might result in impaired integrity of the gastrointestinal tract wall (e.g., Crohn’s disease). Monitor for the development of severe, persistent or worsening abdominal pain; discontinue RELISTOR in patients who develop this symptom. Severe or Persistent Diarrhea Discontinue if severe or persistent diarrhea occurs during treatment. Opioid Withdrawal Consider the overall risk benefit in patients with disruptions to the bloodbrain barrier. Symptoms consistent with opioid withdrawal, including hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, and yawning have occurred in patients treated with RELISTOR. Monitor closely for adequacy of analgesia and symptoms of opioid withdrawal. ADVERSE REACTIONS Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Opioid-Induced Constipation in Adult Patients with Chronic Non-Cancer Pain The safety of RELISTOR tablets was evaluated in a double-blind, placebo-controlled trial in adult patients with OIC and chronic non-cancer pain receiving opioid analgesia. This study (Study 1) included a 12-week, double-blind, placebo-controlled period in which adult patients were randomized to receive RELISTOR tablets 450 mg orally (200 patients) or placebo (201 patients). After 4 weeks of double-blind treatment administered once daily, patients continued 8 weeks of double-blind treatment on an as needed basis (but not more than once daily). The most common adverse reactions in adult patients with OIC and chronic non-cancer pain receiving RELISTOR tablets are shown in Table 4. Adverse reactions of abdominal pain, diarrhea, hyperhidrosis, anxiety, rhinorrhea, and chills may reflect symptoms of opioid withdrawal. Table 4: Adverse Reactions* in 4-Week Double-Blind, Placebo-Controlled Period of Clinical Study of RELISTOR Tablets in Adult Patients with OIC and Chronic Non-Cancer Pain (Study 1) RELISTOR Tablets Placebo Adverse Reaction n = 200 n = 201 Abdominal Pain** 14% 10% Diarrhea 5% 2% Headache 4% 3% Abdominal Distention 4% 2% Vomiting 3% 2% Hyperhidrosis 3% 1% Anxiety 2% 1% Muscle Spasms 2% 1% Rhinorrhea 2% 1% Chills 2% 0%

*Adverse reactions occurring in at least 2% of patients receiving RELISTOR tablets 450 mg once daily and at an incidence greater than placebo. **Includes: abdominal pain, upper abdominal pain, lower abdominal pain, abdominal discomfort and abdominal tenderness.

Table 5: Adverse Reactions* in 4-Week Double-Blind, Placebo-Controlled Period of Clinical Study of RELISTOR Injection in Adult Patients with OIC and Chronic Non-Cancer Pain (Study 2) RELISTOR Injection Placebo Adverse Reaction n = 150 n = 162 Abdominal Pain** 21% 7% Nausea 9% 6% Diarrhea 6% 4% Hyperhidrosis 6% 1% Hot Flush 3% 2% Tremor 1% <1% Chills 1% 0%

*Adverse reactions occurring in at least 1% of patients receiving RELISTOR injection 12 mg subcutaneously once daily and at an incidence greater than placebo. **Includes: abdominal pain, upper abdominal pain, lower abdominal pain, abdominal discomfort and abdominal tenderness. During the 4-week double-blind period, in patients with OIC and chronic non-cancer pain that received RELISTOR every other day, there was a higher incidence of adverse reactions, including nausea (12%), diarrhea (12%), vomiting (7%), tremor (3%), feeling of body temperature change (3%), piloerection (3%), and chills (2%) as compared to daily RELISTOR dosing. Use of RELISTOR injection 12 mg subcutaneously every other day is not recommended in patients with OIC and chronic non-cancer pain. The rates of discontinuation due to adverse reactions during the double-blind period (Study 2) were higher in the RELISTOR once daily (7%) than the placebo group (3%). Abdominal pain was the most common adverse reaction resulting in discontinuation from the double-blind period in the RELISTOR once daily group (2%). The safety of RELISTOR injection was also evaluated in a 48-week, open-label, uncontrolled trial in 1034 adult patients with OIC and chronic non-cancer pain (Study 3). Patients were allowed to administer RELISTOR injection 12 mg subcutaneously less frequently than the recommended dosage regimen of 12 mg once daily, and took a median of 6 doses per week. A total of 624 patients (60%) completed at least 24 weeks of treatment and 477 (46%) completed the 48-week study. The adverse reactions seen in this study were similar to those observed during the 4-week double-blind period of Study 2. Additionally, in Study 3, investigators reported 4 myocardial infarctions (1 fatal), 1 stroke (fatal), 1 fatal cardiac arrest and 1 sudden death. It is not possible to establish a relationship between these events and RELISTOR. Opioid-Induced Constipation in Adult Patients with Advanced Illness The safety of RELISTOR injection was evaluated in two, double-blind, placebo-controlled trials in adult patients with OIC and advanced illness receiving palliative care: Study 4 included a single-dose, double-blind, placebo-controlled period, whereas Study 5 included a 14-day multiple dose, double-blind, placebo-controlled period. The most common adverse reactions in adult patients with OIC and advanced illness receiving RELISTOR injection are shown in Table 6 below. Table 6: Adverse Reactions from all Doses in Double-Blind, PlaceboControlled Clinical Studies of RELISTOR Injection in Adult Patients with OIC and Advanced Illness* (Studies 4 and 5) RELISTOR Injection Placebo Adverse Reaction n = 165 n = 123 Abdominal Pain** 29% 10% Flatulence 13% 6% Nausea 12% 5% Dizziness 7% 2% Diarrhea 6% 2%

*Adverse reactions occurring in at least 5% of patients receiving all doses of RELISTOR injection (0.075, 0.15, and 0.3 mg/kg) and at an incidence greater than placebo. **Includes: abdominal pain, upper abdominal pain, lower abdominal pain, abdominal discomfort and abdominal tenderness. The rates of discontinuation due to adverse reactions during the double-blind, placebo-controlled clinical trials (Study 4 and Study 5) were comparable between RELISTOR (1%) and placebo (2%). Postmarketing Experience The following adverse reactions have been identified during post-approval use of RELISTOR injection. Because reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure. Gastrointestinal Perforation, cramping, vomiting. General Disorders and Administration Site Disorders Diaphoresis, flushing, malaise, pain. Cases of opioid withdrawal have been reported. DRUG INTERACTIONS Other Opioid Antagonists Avoid concomitant use of RELISTOR with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal. Drugs Metabolized by Cytochrome P450 Isozymes In healthy subjects, a subcutaneous dose of 0.3 mg/kg of RELISTOR did not significantly affect the metabolism of dextromethorphan, a CYP2D6 substrate. USE IN SPECIFIC POPULATIONS Pregnancy The use of RELISTOR during pregnancy may precipitate opioid withdrawal in a fetus due to the immature fetal blood brain barrier and should be

used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Advise pregnant women of the potential risk to a fetus. Lactation Because of the potential for serious adverse reactions, including opioid withdrawal, in breastfed infants, advise women that breastfeeding is not recommended during treatment with RELISTOR. In nursing mothers, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use Safety and effectiveness of RELISTOR tablets and injection have not been established in pediatric patients. Geriatric Use In clinical studies of RELISTOR tablets, no overall differences in effectiveness were observed. Adverse reactions were similar; however, there was a higher incidence of diarrhea in elderly patients. In clinical studies of RELISTOR injection, no overall differences in safety or effectiveness were observed between elderly patients and younger patients. Based on pharmacokinetic data, and safety and efficacy data from controlled clinical trials, no dosage adjustment based on age is recommended. Monitor elderly patients for adverse reactions. Renal Impairment In a study of subjects with varying degrees of renal impairment receiving RELISTOR injection subcutaneously, there was a significant increase in the exposure to methylnaltrexone in subjects with moderate and severe renal impairment (creatinine clearance less than 60 mL/minute as estimated by Cockcroft-Gault) compared to healthy subjects. Therefore, a dosage reduction of RELISTOR tablets and RELISTOR injection is recommended in patients with moderate and severe renal impairment (creatinine clearance less than 60 mL/minute as estimated by Cockcroft-Gault). No dosage adjustment of RELISTOR tablets or RELISTOR injection is needed in patients with mild renal impairment (creatinine clearance greater than 60 mL/minute as estimated by Cockcroft-Gault). Hepatic Impairment Tablets In a study of subjects with varying degrees of hepatic impairment receiving a 450 mg dose of RELISTOR tablets, there was a significant increase in systemic exposure of methylnaltrexone for subjects with moderate (Child-Pugh Class B) and severe (Child-Pugh Class C) hepatic impairment compared to healthy subjects with normal hepatic function. Therefore, a dosage reduction of RELISTOR tablets is recommended in patients with moderate (Child-Pugh Class B) or severe (Child-Pugh Class C) hepatic impairment. No dosage adjustment of RELISTOR tablets is needed in patients with mild hepatic impairment (Child-Pugh Class A). Injection There was no clinically meaningful change in systemic exposure of methylnaltrexone compared to healthy subjects with normal hepatic function. No dosage adjustment of RELISTOR injection is needed for patients with mild or moderate hepatic impairment. In patients with severe hepatic impairment, monitor for methylnaltrexone-related adverse reactions. OVERDOSAGE A study of healthy subjects noted orthostatic hypotension associated with a dose of 0.64 mg/kg administered as an intravenous bolus. Monitor for signs or symptoms of orthostatic hypotension and initiate treatment as appropriate. If a patient on opioid therapy receives an overdose of RELISTOR, the patient should be monitored closely for potential evidence of opioid withdrawal symptoms such as chills, rhinorrhea, diaphoresis or reversal of central analgesic effect. NONCLINICAL TOXICOLOGY Carcinogenesis Oral administration of methylnaltrexone bromide at doses up to 200 mg/kg/day (about 81 times the subcutaneous maximum recommended human dose (MRHD) of 12 mg/day based on body surface area) in males and 400 mg/kg/day (about 162 times the subcutaneous MRHD of 12 mg/day) in females and in Sprague Dawley rats at oral doses up to 300 mg/kg/day (about 243 times the subcutaneous MRHD of 12 mg/day) for 104 weeks did not produce tumors in mice and rats. Mutagenesis Methylnaltrexone bromide was negative in the Ames test, chromosome aberration tests in Chinese hamster ovary cells and human lymphocytes, in the mouse lymphoma cell forward mutation tests and in the in vivo mouse micronucleus test. Impairment of Fertility Methylnaltrexone bromide at subcutaneous doses up to 150 mg/kg/day (about 122 times the subcutaneous MRHD of 12 mg/day; about 3.3 times the oral MRHD of 450 mg/day) was found to have no adverse effect on fertility and reproductive performance of male and female rats. Animal Toxicology and/or Pharmacology In an in vitro human cardiac potassium ion channel (hERG) assay, methylnaltrexone caused concentration-dependent inhibition of hERG current. PATIENT COUNSELING INFORMATION See FDA-approved Patient Labeling (Patient Information). To report SUSPECTED ADVERSE REACTIONS, contact Valeant Pharmaceuticals North America LLC at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Based on 9502500, Rev. 07/2016 Salix Pharmaceuticals 8510 Colonnade Center Drive Raleigh, NC 27615 www.salix.com Manufactured for:

Under license from:

Progenics Pharmaceuticals, Inc. Tarrytown, NY 10591 U.S. Patent Numbers: 6,559,158; 8,247,425; 8,420,663; 8,524,276; and 8,956,651 Relistor is a trademark of Salix Pharmaceuticals or its affiliates. RELO.0036.USA.16

Live Medical Conference 6.0–12.0 Ce/CMe credits PAiNWeeKeND™ ReGiONAL CONFeReNCe SeRieS

PAiN MANAGeMeNT FOR THe MAiN STReeT PRACTiTiONeR

2017

painweekend.org

ANAHeiM CA ATLANTA GA BALTiMORe MD BiRMiNGHAM AL CHARLeSTON SC CiNCiNNATi OH DALLAS TX DeNVeR CO

FT. LAUDeRDALe FL HONOLULU HI HOUSTON TX JACKSONViLLe FL KANSAS CiTY MO MiLWAUKee WI MiNNeAPOLiS MN NASHViLLe TN

NeW ORLeANS LA PiTTSBURGH PA PROViDeNCe RI RALeiGH NC SACRAMeNTO CA SALT LAKe CiTY UT SAN DieGO CA SCOTTSDALe AZ

This activity is provided by Global Education Group for 6.0–12.0 AMA PRA Category 1 Credits™. This program is planned in accordance with AANP CE Standards and Policies and AANP Commercial Support Standard.

SeATTLe WA SOUTHFieLD MI ST. LOUiS MO TAMPA FL WOODCLiFF LAKe NJ Cities/states subject to change. Refer to painweekend.org for more information.

enough information to inquire further how this is impacting you, your patients, and your local healthcare facilities every day.

who has spent time with me discussing Kevin L. Zacharoff chronic pain knows I believe chronic pain management ultimately lies in the hands of I am proud to call Dr. Gary Jay a personal clinicians in primary care. There are just not enough specialists to provide friend, and one who always provides fascinating perspectives on chalcare for all who face this often debilitating condition. People who know lenging cases and clinical conundrums in pain management. No disapme are also aware of how important I think pain education is for these pointment in this issue, as Dr. Jay delivers an engaging case presentation practitioners and, most importantly, how everything we discuss should of a bona fide “Catch-22” situation. Without giving too much away, I will ultimately be about how it will enhance safety and efficacy of pain care say that in addition to the diagnostic challenges of this particular case for the patient. In my opinion, if it all doesn’t end up being about the were others presented by the patient’s health insurance organization. patient, then something is off target. This issue of pwj is particularly Can you imagine that? Read on and enjoy. I’m willing to bet there are pleasing as it provides education about pain conditions which often don’t similarities to many situations you have dealt with in clinical practice. get discussed, or factors which might be driving some of what’s happenThis issue’s Pundit Profile is Dr. Sanford Silverman. Dr. Silverman’s path ing in the pain care environment. Welcome to pwj 2017. to anesthesiology and providing care for patients with chronic pain is Although it may not often be discussed, chronic pelvic pain is a condition an interesting one and, as you will read, his passion for helping patients that affects approximately 15% of us women between 18 to 50 years is unsurpassed. We are lucky to know clinicians like Dr. Silverman, who old. Drs. Jennifer Hah and Ravi Prasad present a detailed exploration of hasn’t forgotten the reason he went into medicine to begin with—to this condition, and also discuss the critical role of the primary care clini- make a positive difference in someone’s life. cian in diagnosing and managing this frequently complex and troubling chronic pain problem. The authors provide a comprehensive synopsis of New to this issue of pwj is the Next Generation Profile. It is important to the differential diagnoses for common types of chronic pelvic pain and identify future leaders in the field of pain management who will continue frequently comorbid clinical conditions. What strikes most about this to lead the charge. This inaugural profile focuses on Dr. David Cosio. As article is the fundamental reinforcement of the value of a true interdisci- a psychologist working in a pain clinic, he discusses what drives him, who plinary approach to managing what is often a complicated chronic pain inspires him, and how he contributes to making chronic pain patients’ condition. A case is made that successful treatment includes medical, lives better. We need future leaders, and Dr. Cosio is one of them. physical, and behavioral approaches; no surprise there except for the fact that many women may still go needlessly untreated. Need I say more? I truly think that this first issue of 2017 is important as it spans a number of topics that don’t typically fall into the category of “same old” subject The anesthesiologist in me perked up when reading the article by Drs. matter. Educational resources need to focus on pain conditions that Michael Bonnette, Ikram Malik, and Michael Bottros. It discusses the have been overlooked, clinical conundrums with no apparent solutions, “storm” surrounding the use of opioids in the management of pain, focus- new approaches to managing perioperative pain, and administrative ing on the perioperative period and including past, present, and future forces that affect the “business” of health care. I hope you enjoy this considerations regarding its management. Most of us would find it issue and let’s see what the rest of the year holds. unreasonable to exclude opioid analgesics entirely from the perioperative pain management plan. However, what may not often be considered —Kevin L. Zacharoff md, facip, facpe, faap is the variety of other approaches available to manage perioperative pain in a true “multimodal fashion.” Additionally, patients may fall into a “black hole” regarding the continued prescribing of opioids way beyond Kevin L. Zacharoff is Pain Educator and Consultant and Faculty, Clinical Instructor the perioperative period, because designation of the clinician responsible at suny Stony Brook School of Medicine, Department of Preventive Medicine, in for pain management after the acute/subacute period can often become Stony Brook, New York. unclear. Not surprisingly, the authors make a strong case for education as a part of the solution to many dilemmas that exist in perioperative pain management, along with a safe and efficacious intersection that benefits patients and society. If hcahps is not a familiar term to you, then look no further. Dr. Jeffrey Gudin sheds light on a highly relevant subject as he connects the dots between hospitals, administration, quality of care, pain treatment, patient surveys, and reimbursement. Any of us who have practiced in a hospital setting know how crucially important it is to balance all aspects of patient care, satisfaction, communication, and the business of healthcare. If this is your first exposure to the Hospital Consumer Assessment of Healthcare Providers and Systems, you will likely get

PWJ | www.painweek.org

Q1 | 2017

Michael Bottros md

P.26

Michael Bottros is an Assistant Professor, Division of Pain Management, Department of Anesthesiology, Washington University School of Medicine, and Director of the Acute Pain Service, Barnes-Jewish Hospital in Saint Louis, Missouri. Dr. Bottros coauthored his article with Michael Bonnette, MD, Resident, Physical Medicine and Rehabilitation, Washington University School of Medicine, Saint Louis, Missouri, and Ikram Malik, MD, Fellow, Division of Pain Management, Department of Anesthesiology, at the Washington University School of Medicine, Saint Louis, Missouri.

Jeffrey A. Gudin md

P.34

Jeffrey Gudin is the Director of Pain and Palliative Care at the Englewood Hospital and Medical Center in New Jersey. Dr. Gudin completed his postdoctoral fellowship at the Yale Center for Pain Management and was previously Clinical Instructor in Anesthesiology at the Icahn School of Medicine at Mount Sinai in New York.

Jennifer Hah md, ms

P.18

Jennifer Hah is an Instructor in the Division of Pain Medicine, Department of Anesthesiology, Perioperative, and Pain Medicine at Stanford University in California. Dr. Hah is particularly interested in helping women who experience pelvic pain, and minimizing the adverse effects of prescription opioids through patient education and support. She hopes to develop novel psychotherapeutic interventions to prevent opioid misuse and abuse in patients using prescription opioids for both acute and chronic pain conditions. Dr. Hah is board-certified in Anesthesiology and Pain Medicine.

Gary W. Jay md, faapm, facfei

P.46

Gary Jay is a Clinical Professor in the Department of Neurology, Headache Division, at the University of North Carolina, Chapel Hill. Dr. Jay has published 5 textbooks on headache, pain, and minor traumatic brain injury; published over 140 articles, mostly in peer-review journals, as well as monographs and textbook chapters. He participated in the IMMPACT group for 8 years. Dr. Jay is a speaker in pain medicine, headache, and traumatic brain injury; is a member of the PWJ and 4 other editorial boards and is the Editor in Chief of the online journal Neurological Disorders and Therapeutics.

Ravi Prasad phd

P.18

Ravi Prasad is a psychologist and Associate Division Chief of Pain Medicine at Stanford University in California. He holds additional administrative roles including director of the Stanford Comprehensive Interdisciplinary Pain Program, one of the few academic inpatient pain programs in the United States and training director for the APA-accredited Pain Psychology Postdoctoral Fellowship Program that he developed. He is a member of the Stanford Center for Physician Wellness and Professional Fulfillment and co-director of Peer Support and Resiliency in Medicine (PRIME).

Q1 | 2017

www.painweek.org | PWJ

ACCeSS PAiNWeeK 365 DAYS A YeAR PAINWeek® is an innovative single point of access designed specifically for frontline practitioners, recognized as a trusted resource for the latest pain management news, information, and education. →Visit www.painweek.org to access key opinion leader insights expressed via the following sections: ❶ Expert Opinion ❷ Key Topics ❸ One-Minute Clinician ❹ Pundit Profile ❺ PWJ—PAINWeek Journal

By Jennifer Hah md, ms & Ravi Prasad phd

While these patients [with chronic pelvic pain] may often be referred to “ several specialists, the primary care provider plays a critical role in

PWJ | www.painweek.org

Q1 | 2017

By Jennifer Hah md, ms & Ravi Prasad phd

helping to formulate and integrate an interdisciplinary care plan, involving different disciplines working together to achieve a common goal.”

Q1 | 2017

www.painweek.org | PWJ

WOMeN'S Hea LTH

abstract: The prevalence of chronic pelvic pain in

women 18 to 50 years old is around 15%. However, only one-third of these women currently seek medical care. Also, the average time from presentation to a primary care provider and appropriate specialty referral and diagnosis ranges from 3 to 7 years. To narrow the gap between symptom onset and treatment, multifaceted education of the general public, patients, and providers is essential. As healthcare providers, we need to encourage patients to seek treatment, rather than to suffer in silence. Given the unique challenges associated with treating chronic pelvic pain, for example, in the domain of sexual function, pain in this region presents a unique set of considerations for any provider.

20 PWJ | www.painweek.org

Q1 | 2017

the conglomeration of structures within the pelvis, “ Given chronic pelvic pain can result from disorders of the

urological, gynecological, gastrointestinal, musculoskeletal, and/or nervous system.”

care providers serve an indispensable role for patients with chronic pelvic pain. While these patients may often be referred to several specialists, the primary care provider plays a critical role in helping to formulate and integrate an interdisciplinary care plan, involving different disciplines working together to achieve a common goal. In order to narrow the gap between current and optimal practice, it is essential for healthcare providers to appreciate the epidemiology, risks factors, and etiology of a spectrum of pelvic pain conditions in addition to relevant treatment options. Some of these treatment options could be initiated concurrently with specialist referral. Because chronic pelvic pain is an indication for 15% to 40% of laparoscopies and 12% of hysterectomies in the us, and because a third of women have unclear pathology after diagnostic laparoscopy,1 primary care providers play a critical role in managing pain and encouraging patients to pursue interdisciplinary care. Definitions

chronic pelvic pain is often defined as “nonmalignant pain perceived in the structures related to the pelvis that has been present for greater than 6 months or has a nonacute pain mechanism of a shorter duration.”1 Given the conglomeration of structures within the pelvis, chronic pelvic pain can result from disorders of the urological, gynecological, gastrointestinal, musculoskeletal, and/or nervous system.2 Oftentimes, the pain is an end result of a multitude of factors at play. For example, it is not uncommon for a woman to present with a history of fibromyalgia, irritable bowel syndrome, and painful bladder syndrome. Gynecologic etiologies contributing to chronic pelvic pain can include endometriosis, adhesions, chronic Q1 | 2017

pelvic inflammatory disease, and pelvic congestion syndrome. Urologic causes include interstitial cystitis or painful bladder syndrome, chronic urinary tract infections, or kidney stones. Gastrointestinal etiologies can refer to the pelvis including irritable bowel syndrome, chronic appendicitis, inflammatory bowel disease, or chronic constipation. Musculoskeletal causes are numerous and can contribute as pelvic floor dysfunction, degenerative disc disease, or sacroiliac joint disorders.1 Pelvic pain encompasses pain arising from the visceral or somatic nervous system from the T10 level and below. The pelvic floor refers to the fascial and muscle layers that span the bony outlet of the pelvis. It is important to note here that patients with pelvic floor dysfunction may not necessarily have pain. www.painweek.org | PWJ

WOMeN'S HeaLTH

The Pain Specialist

With referral to a pain medicine specialist, patients undergo a history and physical examination with an additional focus on targeting peripheral nerve entrapments or neuralgia. The branches of the lumbosacral plexus are particularly relevant contributors to pelvic pain. Another important concept is viscerosomatic convergence. Viscerosomatic convergence results in the pelvis as visceral afferents reach the upper lumbar or lower thoracic spinal cord at the same levels as somatic nerves. Specifically, sensory convergence from autonomic afferents can lead to somatic symptoms and vice versa. An example is the development of myofascial trigger points in somatic tissue, such as the levator ani muscles in response to increased nociceptive visceral input from the rectum. The iliohypogastric nerve is formed from branches of t12 and l1 and converges on dorsal horn structures shared with the ipsilateral ovary and distal fallopian tube.3 It provides sensation to the groin and pubic symphysis. Similarly, the ilioinguinal nerve is formed from branches of t12 and l1 and converges on dorsal horn structures shared with proximal fallopian tubes and the uterine fundus. This nerve provides sensation to the groin, mons, labia, and inner thigh.3 Mechanisms of injury to these nerves include entrapment by a suture at the lateral edge of a Pfannenstiel incision or trauma during needle bladder suspension. Thus, surgical history both in the immediate past and more remotely are very relevant to determining the etiology of a patient’s pelvic pain. Upon identification of potential peripheral nerve target, which could explain a patient’s pelvic pain, many of these nerves can be blocked under ultrasound guidance. The ilioinguinal and iliohypogastric nerves are an example of peripheral nerves that can be targeted under ultrasound guidance with subsequent injection of a combination of local anesthetic and steroid. The genitofemoral nerve formed from branches of l1 and l2 converges on dorsal horn structures shared with the proximal fallopian tube and uterine fundus. The genital branch innervates the skin of the mons pubis and labia majora (anterior scrotum in men), and is often the intended target of genitofemoral nerve blocks used to target chronic pelvic pain. The femoral branch innervates the skin over the femoral triangle. One modality of injury to the nerve may be due to postappendectomy perineural fibrosis as this nerve has a long course over the psoas muscle.3 The pudendal nerve converges on dorsal horn structures shared with the cervix, uterosacral, and vulvovaginal region. The nerve is formed from branches of s2 to s4, and has 3 terminal branches: the dorsal nerve of the penis/clitoris, a perineal branch, and an inferior rectal branch. The pudendal nerve provides motor innervation to both the external anal and urethral sphincters, the vaginal vestibule as well as the majority of the somatic innervation to the pelvic floor. However, significant cross-talk between nerves of the pelvis exist.4 Thus, failure of a diagnostic pudendal nerve block to provide relief should

PWJ | www.painweek.org

warrant consideration of additional nerve targets. Other available treatments for peripheral neuralgias include the use of pulsed radiofrequency neuromodulation or peripheral nerve stimulation. The pudendal nerve can be entrapped anywhere along its course. Commonly identified entrapments areas include the greater sciatic notch, the ischial spine, Alcock’s canal, and the distal branches.5 The mechanisms of injury to the pudendal nerve are numerous including childbirth (prolonged 2nd stage of labor, 3rd degree tear through the perineal body), surgery (sacrospinous vaginal vault suspension, laser to the vulva), and trauma (straddle injuries, bicycle riding, repeated squatting, and constipation).3

Specific Diagnoses Endometriosis Endometriosis affects 5% to 10% of women of reproductive age and involves growth of endometrial glands and stroma outside of the uterus.6 The average age of women affected ranges from 25 to 35 years. These patients are typically nulliparous, involuntarily infertile, and report secondary dysmenorrhea several years after the onset of menarche in addition to pelvic pain.6 Associated symptoms include dysmenorrhea, dyspareunia, heavy menstrual bleeding, nonmenstrual pelvic pain, pain at ovulation, dyschezia, and dysuria.6 Treatment commonly includes a combination of nsaids and hormonal therapy ranging from combined oral contraceptive pills, gonadotropin releasing hormone agonists, and progestins. In severe cases, surgery such as laparoscopic surgical removal of endometriosis is an effective modality for treating pain.7 Although endometriosis is a histologic diagnosis, initiation of treatment for suspected endometriosis should not be delayed until after surgery. As an adjunct to these treatments, pain specialists can offer interventions to target the visceral afferents innervating the pelvis. For example, the superior hypogastric plexus is located anterior to the l5 vertebral body and sacrum at the bifurcation of the common iliac vessels. Sensory fibers transmit nociceptive impulses from the uterus, cervix, fallopian tubes, bladder, and rectum. These visceral afferents have cell bodies in the dorsal root ganglia of t10 to l2. In addition, the plexus contains parasympathetic nerves from s2 to s4.8 A superior hypogastric plexus block can result in significant pain relief for patients with endometriosis,9 and can serve to provide much needed relief during significant pain flares.

Pelvic Congestion Syndrome Pelvic congestion syndrome involves enlarged venous complexes of reproductive tissue with associated impaired circulation and drainage. Symptoms associated with this condition include dull aching pain exacerbated by increased venous pressure (heavy lifting, Valsalva maneuvers). Patients most often report symptoms of deep dyspareunia, postcoital aching Q1 | 2017

A superior hypogastric plexus block can result “ in significant pain relief for patients with endometriosis, and can serve to provide much needed relief during significant pain flares.”

that can last from hours to days, and dysmenorrhea up to one week before menses.10 Pelvic venography is the gold standard for diagnosis, but pelvic ultrasound is often used as a first line diagnostic test to detect pelvic congestion syndrome. Treatments range from hormonal therapies such as medroxyprogesterone acetate, to surgical interventions—ovarian vein ligation, uterine suspension, ovarian and pelvic vein embolization. An important modality to managing pain associated with pelvic congestion syndrome includes physical therapy with manual lymphatic drainage techniques.11

Vulvodynia Vulvodynia is defined as chronic pain or discomfort involving the vulva for more than 3 months and for which no obvious etiology can be found. The lifetime prevalence for vulvodynia is relatively static up till age 70 at 8%. The typical age of affected women ranges from 20 to 40 years. Currently, provoked vestibulodynia is the most common cause of sexual pain in women less than 30 years old.12 Many underlying mechanisms for vulvodynia have been proposed. Often, there is an initial inciting event, such as a yeast infection, with resulting inflammation thought to lead to altered pain processing. Alternate proposed mechanisms include stretch injury to the levator ani nerve or pudendal nerve during childbirth, or straddle injuries. Treatment for this condition is multifaceted. As women with a history of anxiety or depression are 4 times more likely to develop provoked vestibulodynia, supportive psychotherapy, cognitive behavioral therapy, and sexological counseling are important considerations in the management of this condition. Topical treatments with lidocaine gel or estrogen cream may be beneficial. Oral medications to trial include antineuropathics such as tricyclic antidepressants, gabapentin, or pregabalin. Interventions such as pudendal nerve blocks may be helpful to reduce the vulvar pain. Physical therapy modalities such as biofeedback can be used to decrease pelvic floor hypertonicity along with manual or electrotherapeutic input to the thoracolumbar and sacral areas. In addition to engaging in physical therapy, patients may also trial superficial perineal massage at home to relax the pelvic floor.12 Q1 | 2017

Interstitial Cystitis/ Painful Bladder Syndrome Interstitial cystitis or painful bladder syndrome has sustained an evolution in diagnostic criteria over the years.13 Currently the American Urological Association defines the condition as “an unpleasant sensation (pain, pressure, discomfort) perceived to be related to the urinary bladder, associated with lower urinary tract symptom(s) of more than 6 weeks duration, in the absence of infection or other identifiable causes.”14,15 Patients present with symptoms of urinary frequency, urgency, and nocturia. The pain of bladder filling is partially or completely relieved by voiding frequency, and pain can encompass suprapubic, urethral, lower abdominal, and low back areas. Patients with this condition often present with multiple overlapping pain syndromes including fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, temporomandibular disorder, migraines, chronic pelvic pain, vulvodynia, and low back pain.16,17 Patients often experience significant limitations in activities of daily living (shopping, travel, exercise), decreased quality of life, increased sleep dysfunction, increased pain catastrophizing, and elevated anxiety.18 Underlying mechanisms of this condition are now thought to mirror other chronic pain conditions with increased central sensitization over time. As a result, the American Urological Association recommends that “pain management should be considered throughout the course of therapy with the goal of maximizing function and minimizing pain and side effects.”15 Interdisciplinary management is paramount in managing pain in patients with interstitial cystitis/painful bladder syndrome. Patient education and support should center on self-care and behavioral modification. A bladder re-education protocol of voiding by the clock rather than voiding based on urgency can help to decrease frequent trips to the restroom. Appropriate physical therapy centered on connective tissue manipulation and pelvic floor myofascial trigger point release or biofeedback can help to relax the pelvic floor. It is important to note that pelvic physical therapy in patients with interstitial cystitis does not center on pelvic floor strengthening exercises. Instead, measures to increase proprioception and www.painweek.org | PWJ

WOMeN'S HeaLTH

relax the pelvic floor will augment pain relief. Patients can try double-voiding as an exercise to facilitate proprioceptive awareness of pelvic floor movement. After voiding, patients remain seated on the toilet and relax or drop the pelvic floor again as if to initiate voiding.19 With regard to medications, certain antineuropathic agents have shown promise in treating patients with interstitial cystitis. In a study of 50 patients randomized to amitriptyline or placebo, amitriptyline titrated to a maximum dose of 100 mg resulted in 42% of patients experiencing a 30% or greater decrease in interstitial cystitis related symptoms.20 Similarly, in a multicenter, double blind, randomized, placebo controlled trial, a subgroup of patients reaching a dose of 50 mg daily of amitriptyline had a global response assessment rate of 66% compared to 47% in the placebo group.21 Other antineuropathics such as gabapentin alone or in combination with amitriptyline have led to reductions in vas (visual analogue scale) scores in patients with interstitial cystitis.22

Interdisciplinary Care for Pelvic Pain Moving from specific diagnoses to a broader perspective, pelvic pain can be categorized into 2 primary domains: acute and chronic. In acute pain, the hurtful sensations that a person experiences can be a sign of active harm occurring in the body that requires some sort of immediate action to prevent additional damage. It often has a clear, single cause and the treatment pathway usually calls for resting or immobilizing the injured body part, medication management, and potentially surgical/procedural intervention. By definition, acute pain is temporary and will go away. Unlike acute pain, chronic pelvic pain often has an ambiguous cause and multiple contributing factors. Even though the pain condition can be named, the exact mechanism that contributes to the chronicity is often unknown (Table). Regardless of the cause, it is known that certain substances, emotional states, quality of sleep, and stressors can all influence the actual experience of pain.

There is unfortunately not a way to fix all chronic pelvic pain conditions; however, there are several steps that people can take to manage their condition. The management approach to pain is similar to the treatment for other chronic health conditions that have no cure, such as diabetes. There is no surgery, pill, or injection that results in a 100% cure of diabetes; rather, people diagnosed learn to manage. Management of diabetes requires a combination of efforts including (but not limited to) monitoring blood sugars, taking medication or insulin, getting regular exercise, diet modification, and observing wounds. If a diabetic engages in the above behaviors, he/she can have a very high quality of life despite the presence of the condition. Chronic pelvic pain management is very similar to diabetes management in that both require a combination of treatments to maximize outcomes. In the case of chronic pelvic pain, there are 3 primary areas that should be addressed: ● Medical optimization refers to addressing all medical aspects of a chronic pain condition and is usually implemented by physicians or physician extenders (physician assistants, nurse practitioners, etc). Is there a role for surgery, injections, or implantable devices? Is the person on too much medication, too little, or the most appropriate drugs for his/her condition? These are the types of questions that are addressed in the realm of medical optimization. ● Physical reconditioning refers to improving aspects of physical functioning. When people experience pain in a part of their bodies, there is a natural tendency to guard or protect this region out of fear of reinjury or avoidance of discomfort. Unfortunately, such behaviors can result in a worsening of pain due to the effect on the muscles. Additionally, some of the ways that we compensate (overuse of other muscle groups, changes in posture and body mechanics, etc) can lead to a worsening of pain as well. Rehabilitation specialists such as physical therapists can help persons living with pain learn how to maintain strength in the part(s) of their body affected by pain and teach them healthy compensation mechanisms.

Table. Acute vs Chronic Pain8 Acute Pain

Chronic Pain

Meaning

Hurt = Harm

Hurt ≠ Harm

Cause

Clear, singular

Ambiguous, multifactorial

Treatment

▸▸ Fixed endpoint

▸▸ No endpoint

▸▸ Medications and interventions often lead to cure

▸▸ Interdisciplinary approach necessary for management

24 PWJ | www.painweek.org

Q1 | 2017

● Behavioral/lifestyle modification refers to virtually everything else not covered by the above specialty areas. Studies have illustrated that substances, stressors, and emotional states (such as depression and anxiety) can all contribute to and worsen pain conditions. While behavioral and psychological factors may not be the cause of a pelvic pain condition, they can influence the overall pain experience and even undermine the effectiveness of medically based treatment interventions. Helping individuals understand these factors, how they contribute to pain, and how to break the cycle in which pain and stress feed off each other is typically the role that a psychologist or other mental health practitioner plays in the treatment team. Optimum pelvic pain management requires a combination of all of the above working together. This team approach is often referred to as interdisciplinary care, and involves the efforts of several different disciplines working with one another to achieve a common goal. Focusing only on one aspect of the 3 categories will not likely lead to favorable outcomes: this would be similar to a diabetic who tried to manage his/her condition by relying solely on medications and not making changes in any other areas. Whereas acute pain treatment often includes passive approaches to care in which there is minimal effort required of the patient (taking medication, resting, etc), chronic pain management is an active approach. Patients are the most central part of the treatment team, and they have to be willing to make changes in the areas identified above if they want their situation to improve. Simply understanding the above connections is not enough: patients have to act on this knowledge in order to maximize their outcomes and achieve higher quality of life.

Conclusion

Although the discomfort associated with chronic pelvic pain conditions is not usually a sign of acute harm within the body, the impact it can have on a patient’s physical and psychological well-being is profound. These adverse effects are further amplified by the delay between pelvic pain symptom onset and initiation of treatment. Clinicians can play a significant role in reducing these negative experiences by providing patients with validation of their predicament, education on pain etiology and management, and initiation of a comprehensive treatment plan. Outcomes are maximized when using interdisciplinary approaches to care that incorporate the multitude of pharmacologic and procedural interventions with physical, behavioral, and psychological strategies and techniques. References 1. Stacy J, Frawley H, Powell G, et al. Persistent pelvic pain: rising to the challenge. Aust N Z J Obstet Gynaecol. 2012;52:502–507. 2. Yunker A, Sathe NA, Reynolds WS, et al. Systematic review of therapies for noncyclic chronic pelvic pain in women. Obstet Gynecol Survey. 2012;67:417–425.

Q1 | 2017

3. Apte G, Nelson P, Brismee JM, et al. Chronic female pelvic pain— part 1: clinical pathoanatomy and examination of the pelvic region. Pain Pract. 2012;12:88–110. 4. Wallner C, van Wissen J, Maas CP, et al. The contribution of the levator ani nerve and the pudendal nerve to the innervation of the levator ani muscles; a study in human fetuses. Eur Urol. 2008;54:1136–1142. 5. Filler AG. Diagnosis and treatment of pudendal nerve entrapment syndrome subtypes: imaging, injections, and minimal access surgery. Neurosurg Focus. 2009;26:E9. 6. Bruner-Tran KL, Herington JL, Duleba AJ, et al. Medical management of endometriosis: emerging evidence linking inflammation to disease pathophysiology. Minerva Ginecol. 2013;65:199–213. 7. Johnson NP, Hummelshoj L, World Endometriosis Society Montpellier Consortium. Consensus on current management of endometriosis. Hum Reprod. 2013; 28:1552–1568. 8. Fishman S, Ballantyne J, Rathmell JP, et al. Bonica’s Management of Pain. 4th ed. Baltimore, MD: Lippincott, Williams & Wilkins; 2010: 614–615. 9. Kanazi GE, Perkins FM, Thakur R, et al. New technique for superior hypogastric plexus block. Reg Anesth Pain Med. 1999;24:473–476. 10. Perry CP. Current concepts of pelvic congestion and chronic pelvic pain. JSLS. 2001;5:105–110. 11. Nelson P, Apte G, Justiz R, 3rd, et al. Chronic female pelvic pain—part 2: differential diagnosis and management. Pain Pract. 2012;12:111–141. 12. Sadownik LA. Etiology, diagnosis, and clinical management of vulvodynia. Int J Womens Health. 2014;6:437–449. 13. Hanno PM. Interstitial cystitis-epidemiology, diagnostic criteria, clinical markers. Rev Urol. 2002;4 suppl 1:S3-S8. 14. Hanno PM, Burks DA, Clemens JQ, et al. AUA guideline for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome. J Urol. 2011; 185:2162–2170. 15. Hanno PM, Erickson D, Moldwin R, et al, American Urological Association. Diagnosis and treatment of interstitial cystitis/bladder pain syndrome: AUA guideline amendment. J Urol. 2015;193:1545–1553. 16. Warren JW, Clauw DJ, Langenberg P. Prognostic factors for recent-onset interstitial cystitis/painful bladder syndrome. BJU Int. 2013;111:E92-E97. 17. Bullones Rodriguez MA, Afari N, Buchwald DS, National Institute of Diabetes, Digestive, Kidney Diseases Working Group on Urological Chronic Pelvic Pain. Evidence for overlap between urological and nonurological unexplained clinical conditions. J Urol. 2013;189:S66-S74. 18. Offiah I, McMahon SB, O’Reilly BA. Interstitial cystitis/bladder pain syndrome: diagnosis and management. Int Urogynecol J. 2013;24:1243–1256. 19. FitzGerald MP, Payne CK, Lukacz ES, et al. Randomized multicenter clinical trial of myofascial physical therapy in women with interstitial cystitis/painful bladder syndrome and pelvic floor tenderness. J Urol. 2012;187:2113–2118. 20. van Ophoven A, Pokupic S, Heinecke A, et al. A prospective, randomized, placebo controlled, double-blind study of amitriptyline for the treatment of interstitial cystitis. J Urol. 2004;172:533–536. 21. Foster HE, Jr, Hanno PM, Nickel JC, et al. Effect of amitriptyline on symptoms in treatment naive patients with interstitial cystitis/painful bladder syndrome. J Urol. 2010;183:1853–1858. 22. Lee JW, Han DY, Jeong HJ. Bladder pain syndrome treated with triple therapy with gabapentin, amitriptyline, and a nonsteroidal anti-inflammatory drug. Int Neurourol J. 2010;14:256–260.

www.painweek.org | PWJ

By Michael Bonnette md/Ikram Malik md/Michael Bottros md

PHa RMaCOTHeRa PY

abstract: Pain is an unfortunate part of human existence,

and the pursuit of relief has been an integral part of the medical profession for thousands of years. Researchers and practitioners have continued to innovate and create newer research platforms in the pursuit of improving our understanding of the basic physiologic mechanisms of pain. Over the last century the development of current pain management practices was pursued with good intentions, but today, the United States is in the midst of an opioid crisis. Much of the focus on this debate has been on outpatient prescription drugs and the prescribing patterns of physicians. Only recently has attention been drawn to the perioperative setting and its potential contribution to our current climate. Acute postsurgical pain is unique in that we as medical professionals subject our patients to an expected amount of pain in the hope of providing an improved outcome as a whole; however, if not managed properly, evidence shows it can add to the current epidemic.

28 PWJ | www.painweek.org

Q1 | 2017

History of opioid use

opium, its derivatives, and cocaine were mostly unregulated and by the end of the 19th century opium and morphine were commonly used in the United States both medically and recreationally.1 These drugs were used for many maladies ranging from cough to gastrointestinal upset. By 1914, it was thought that 1 in 400 Americans were addicted to some form of opium. While possibly hidden reasons for its approval are still debated, the Harrison Narcotics Tax Act was passed to United States federal law in 1914 with the goal of regulating and taxing importing, manufacturing, and distributing of opium and cocaine.2 In effect, and partly due to addiction not being considered a disease at the time, physicians who prescribed maintenance doses to addicted patients risked loss of license, arrest, or imprisonment. due to the fear of prosecution, physicians stopped prescribing opioid medications, eventually leading to an undertreatment of legitimate pain.3 Over the next several decades, studies showing benefits of opioid therapy along with efforts by advocacy groups for the humane treatment of pain culminated in 1997 with the Federation of State Medical Boards’ adoption of the “Intractable Pain Statutes” in their Model Policy on the use of Opioid Analgesics in the Treatment of Chronic Pain. This policy recognized the use of opioid analgesics as essential for the treatment of acute and chronic pain “due to cancer or noncancer origins.” The policy also stated that “physicians should not fear disciplinary action…for prescribing, dispensing, or administering controlled substances, including opioid analgesics.”4 Unfortunately, this lead to physicians extrapolating the unidimensional and unimodal approach to treatment with opioids for end of life and cancer pain to treat chronic noncancer pain. Disappointingly, this should not come as a surprise to many. In a 2011 study at Johns Hopkins by Mezei et al, United States medical schools were found to provide a mean of only 11.13 (+/- 8.23) cumulative teaching hours of pain education, with a median of 9 hours. This was less than half of what Canadian medical schools were providing. In addition, less than 4% of North American medical schools reported having integrated Q1 | 2017

pain courses.5 By contrast, US veterinarian schools spend on average 500% more time on pain management principles. This study illuminated the lack of cumulative pain education and the fragmented fashion in which these courses were taught. This lack of education is reflected in data from the National Council on Compensation Insurance for Workers Compensation indicating that 9 of the top 20 drugs paid for were opioid analgesics. Of all opioid analgesics, oxycodone was the most common active ingredient at nearly 45% of opioid prescriptions, and the brand name OxyContin® was 25.5% of all opioids prescribed, holding the largest share paid for any single drug.6 A Cochrane Review published in 2010 by Nobel et al examined the use of long-term opioids in chronic noncancer pain. Sixty-two randomized control trials were included in this meta-analysis and the authors found opioids to be more effective than placebo for nociceptive and neuropathic pain, but there was only weak evidence for long-term use and no evidence for use over 1 year. Patients were divided into groups based on formulation—oral, transdermal, intrathecal. There were a significant number of patients who discontinued use due to adverse effects (22.9%, 12.1%, 8.9%, respectively) or insufficient pain relief (10.3%, 7.6%, 5.8%, respectively). In this review there was inconclusive evidence if quality of life or functionality were improved.7 www.painweek.org | PWJ

PHaRMaCOTHeRaPY

As the amount of legitimate use of opioid analgesics increases, the prevalence of adverse effects leading to ed visits also increases.”

Despite this, the increased shift to using opioids for chronic noncancer pain has not improved acute postoperative pain control. A 2003 study by Apfelbaum et al surveyed 250 adults after surgery regarding postoperative pain control and compared their data to a previous survey in 1995 by Warfield and Kahn.8 The authors found similar percentages of patients suffered from moderate and severe pain in both studies, while more patients experienced “extreme” pain in the 2003 study (18%) compared to the 1995 study (8%).9 Inadequately managed postsurgical pain can burden healthcare systems with increased complications, resource utilization, and longer hospital stays with higher cost. There are also higher readmission rates and the potential for progression from acute to chronic pain.10,11

Persistant opioid use

Of concern is the striking number of patients who continue with persistent opioid use long after their surgeries. A retrospective study by Alam et al12 looked at nearly 400,000 opioid naïve patients undergoing low-risk surgeries (cataract surgery, laparoscopic cholecystectomies, transurethral resection of the prostate, varicose vein stripping) and evaluated their postoperative pain management. It was found that even after these relatively minor procedures, 7.1% of patients were prescribed opioid analgesics within 7 days of the procedure and about 10% of those continued to use these medications after 1 year. Even more concerning was that medication prescribed at 1 year had escalated to a more potent opioid analgesic in many cases. In a different study by Clarke et al, looking at prolonged opioid use after major surgery, 39,140 opioid naïve patients were followed with a main outcome of prolonged opioid use after discharge (>90 days).13 Of these patients, 49.2% were discharged with opioids and 3.1% continued to use after 90 days. Although 3.1% may seem small, if extrapolated to the 2010’s total number of inpatient surgeries performed (51.4 million), 1.6 million patients may potentially require continued opioid use after surgery annually.14 Interestingly, this study additionally found no difference in prolonged opioid use among those

30 PWJ | www.painweek.org

undergoing minimally invasive vs open surgery for thoracic and abdominal procedures.

Increased unused opioids and the link with illicit drug use

In the 2013 National Survey on Drug Use and Health, prescription pain medications were second only to marijuana as the most abused drugs, and the number of individuals abusing pain relievers was more than cocaine, heroin, and stimulants combined.15 As seen in the Table, this data also demonstrated that the vast majority of pain medications for nonmedical use were obtained from legitimate prescriptions. Contrary to what physicians think, a 2016 survey of primary care physicians about opioid abuse revealed that 69% of primary care physicians believe the most common source of these drugs is from multiple physicians, when in actuality less than 5% of abused pain medications are the result of doctor shopping.16 This is not to say that primary care physicians are any more responsible than other physicians, as seen in a 2015 survey among hand surgeons.17 This study showed surgeons had statistically significant less concern than primary care physicians regarding adverse events from opioids such as addiction, tolerance, impaired cognition, sedation, motor vehicle accidents, or death. This lack of concern can be seen when looking more into the prescribing practices in the modern postoperative setting. A study by Rodgers et al18 explored opioid prescriptions after elective upper extremity surgeries in 250 patients. They frequently received 30 pills, but 53% of patients required only 2 days or less of opioid analgesics, leaving a mean of 19 pills per subject reported as unused. Likewise, a 2011 survey by Bates et al, looked at opioids prescribed and used after several different urological procedures.19 Of the dispensed medications, only 58% were consumed, 67% of participates had a surplus, and 92% received no disposal instructions. Of the subjects with a surplus, 91% kept the medication at home, 6% threw it in the trash, 2% flushed it down the toilet, and only 1% returned the medication to the pharmacy. Q1 | 2017

Table. Source Where Opioid Pain Relievers Were Obtained for Nonmedical Use: 2012–2013 Source Where USER Obtained

Source Where FRIEND/RELATIVE Obtained

Free from friend/relative

53.0

1 doctor

83.3

1 doctor

21.2

Free from friend/relative

5.1

Bought/took from friend/relative

14.6

Bought/took from friend/relative

4.9

Drug dealer/stranger

4.3

Drug dealer/stranger

1.4

Other*

4.3

More than 1 doctor

3.3

More than 1 doctor

2.6

Bought on internet

0.3

Bought on internet

0.1

Other*

1.2%

*Other includes: wrote fake prescription, stole from doctor’s office/clinic/hospital/pharmacy, and some other way. Used with permission from Substance Abuse and Mental Health Services Administration, Results from the 2013 National Survey on Drug Use and Health: Summary of National Findings. Based on chart available at: www.samhsa.gov/data/sites/default/files/NSDUHresultsPDFWHTML2013/Web/ NSDUHresults2013.pdf.

These prescribing practices are not exclusive to just the adult patient population. Just as alarming, if not more, is the adolescent population at risk with current prescribing practices. A longitudinal study by Veliz et al following 1540 adolescents found that those who participated in organized sports were twice as likely to be prescribed opioids, 10 times as likely to misuse these medications by taking too much, and 4 times as likely to misuse the medications to get high.20 The authors concluded that males participating in sports have greater access to opioid analgesics and greater risk of misuse and abuse than other populations.

The transition to heroin

Numerous studies have been published about the link between opioid misuse and heroin use. Among them, Inciardi et al published the results of an ultrarapid assessment, which brought together addicts, police, regulatory officials, drug dealers, and pill brokers into focus groups to discuss their stories.21 It was found that the popularity of using prescription opioid analgesics was founded in the perception that they were less stigmatizing, less dangerous, and less subject to legal consequences. Most drug abusers admitted that opioids acted as a gateway to their current addiction, lower cost heroin.

A study by Dasqupta et al exploring the association of nonmedical use of prescription opioids found that certain opioid analgesics were more likely to be abused than others.22 The study used dawn (Drug Abuse Warning Network) data and showed the relationship between the number of emergency department (ed) visits and the amount of opioid prescribed. As the amount of legitimate use of opioid analgesics increases, the prevalence of adverse effects leading to ed visits also Q1 | 2017

increases. Although some analgesics (fentanyl, hydromorphone, hydrocodone, oxycodone, and methadone) have a higher correlation between ed visits and the amount prescribed, when corrected for relative potency there is a linear relationship between ed visits and amount prescribed. As a result of the growing concern for opioid misuse and abuse, in 2015 the Joint Commission issued a revision to pain management standards, stating, “treatment strategies for pain may include pharmacologic and nonpharmacologic approaches. Strategies should reflect a [patient]-centered approach and consider the patient’s current presentation, the healthcare provider’s clinical judgment, and the risk and benefits associated with the strategies, including potential risk of dependency, addiction, and abuse.”23

The opportunity

Improvements in education are necessary to change the current practices of opioid analgesic prescription. Stanek et al published the results of their educational program with an aim to improve postoperative opioid prescribing practices among hand surgeons.24 After a brief educational session, there was a 15% to 48% decrease in the amount of postoperative pills prescribed by hand surgeons. Of note, while prescription amounts decreased, there was no evidence of patients seeking out refills. For surgical patients, the goal should not only be to reduce their amount of postsurgical pain but also to enhance their recovery after surgery.25 While many factors contribute to this process, some significant areas to address are setting the right patient expectations with preadmission counseling, www.painweek.org | PWJ

PHaRMaCOTHeRaPY

… …while prescription amounts decreased, there was no evidence of patients seeking out refills.”

reducing the dependency on opioids through nonopioid adjuvant analgesics, preventing nausea and vomiting, and encouraging early mobilization. Risk stratification may greatly help identify patients at risk for opioid abuse. Rice et al identified the following key risk factors (odds ratio >2): at least one prior prescription of buprenorphine or methadone, at least one diagnosis of nonopioid drug abuse, prior opioid prescriptions, a family member diagnosed with opioid abuse, mental illness, and hepatitis.26 Perioperative multimodal analgesia includes the use of adjuvant medications such as gabapentin and pregabalin that have been shown in various studies to reduce the need for opioids.27 Preventive acetaminophen showed a reduction in 24-hour opioid consumption, lower pain scores at 1 hour, and a lower incidence of postoperative vomiting.28 In a recent review, Gupta et al found that nonsteroidal anti-inflammatory drugs (nsaids) are safe and effective in the treatment of postoperative pain.29 They were shown to increase patient satisfaction, decrease opioid requirements, and minimize opioid induced adverse events. Intravenous ketamine can be an effective adjunct for postoperative analgesia,30 whose benefit was observed in painful procedures, including upper abdominal, thoracic, and major orthopedic surgeries. The use of regional anesthesia can help enhance the recovery process and reduce the need for opioid analgesics. A recent Cochrane Review explored the use of epidural local anesthetics vs opioid based analgesic regimens postoperatively after abdominal surgeries.31 Epidural analgesia reduced the time to first flatus and passage of first stool, reduced nausea and vomiting, and lowered visual analog scale (vas) pain scores. Regional anesthesia not only reduces immediate complications after surgery but also decreases the development of chronic pain syndromes. A systematic review by Andreae et al found that epidural analgesia was more effective at preventing persistent postthoracotomy pain syndromes, and paravertebral blocks were superior to traditional opioid analgesia in preventing post-mastectomy pain syndromes.32

PWJ | www.painweek.org

Conclusion

The role of opioids in pain management is contentious. With the current controversy, it can be easy to swing the pendulum in the completely opposite direction. The purpose of this article is not to debate if perioperative opioids are appropriate—far from it. The intent is to elucidate historical and current prescribing pattern problems. Based on population health statistics, a large number of patients continue postoperative opioid use indefinitely. In addition, current postoperative prescribing practices across specialties are flooding the community with unused opioid analgesics. These unused opioid analgesics are the main source of abused or diverted drugs, which appear to act as a gateway to heroin and cocaine use. Extending our reach beyond solely using opioids in perioperative pain management by using a multimodal approach can impact both patients and society and even potentially decrease persistent postsurgical pain syndromes. References 1. Agnew J. Alcohol and Opium in the Old West: Use, Abuse, and Influence. Jefferson, North Carolina: McFarland & Company; 2010. 2. Brecher EM. Licit and Illicit Drugs: The Consumer Union Report on Narcotics, Stimulants, Depressants, Inhalants, Hallucinogens, and Marijuana. Boston, Massachusetts: Little Brown; 1972. 3. Terry CE. The Harrison Anti-Narcotic Act. Am J Public Health (NY). 1915;5(6):518. 4. The Federation of State Medical Boards of the United States, Inc. Model guidelines for the use of controlled substances for the treatment of pain. S D J Med. 1999;52(1):25–27. 5. Mezei L, Murinson BB, Johns Hopkins Pain Curriculum Development Team. Pain education in North American medical schools. J Pain. 2011;12(12):1199–1208. 6. Lipton B. National Council on Compensation Insurance. Workers Compensation Prescription Drug Study: 20Update. Available at: www.ncci.com/Articles/ Documents/II_Prescription_Drug_Study-NCCI_AIS_2013.pdf. 7. Noble M, Treadwell JR, Tregear SJ, et al. Long-term opioid management for chronic noncancer pain. Cochrane Database Syst Rev. 2010;(1):CD006605. 8. Warfield CA, Kahn CH. Acute pain management: programs in U.S. hospitals and experiences and attitudes among U.S adults. Anesthesiology 1995;83:1090–1094.

Q1 | 2017

9. Apfelbaum JL, Chen C, Mehta SS, et al. Postoperative pain experience: results from a national survey suggest postoperative pain continues to be undermanaged. Anesth Analg. 2003;97(2):534–540.

21. Inciardi JA, Surratt HL, Beard RA. Prescription opioid abuse and diversion in an urban community: the results of an ultrarapid assessment. Pain Med. 2009;10(3):537–548.

10. Practice guidelines for acute pain management in the perioperative setting: an updated report by the American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology. 2004;100:1573–1578.

22. Dasgupta N, Kramer ED, Zalman MA, et al. Association between non-medical and prescriptive usage of opioids. Drug Alcohol Depend. 2006;82:135–142.

11. Perkins FM, Kehlet H. Chronic pain as an outcome of surgery. A review of predictive factors. Anesthesiology. 20093:1123–1133. 12. Alam A, Gomes T, Zheng H, et al. Long-term analgesic use after low-risk surgery: a retrospective cohort study. Arch Intern Med. 2012;172(5):425–430. 13. Clarke H, Soneji N, Ko DT, et al. Rates and risk factors for prolonged opioid use after major surgery: population based cohort study. BMJ. 2014;348:g1251. 14. Center for Disease Control and Prevention. Number of Procedures: fact sheet. Available at: www.cdc.gov/nchs/data/nhds/4procedures/2010pro4_ numberprocedureage.pdf. 15. Substance Abuse and Mental Health Services Administration, Results from the National Survey on Drug Use and Health: Summary of National Findings. Available at: www.samhsa.gov/data/sites/default/files/NSDUHresultsPDFWHTML2013/Web/NSDUHresults2013.pdf. 16. Hwang CS, Turner LW, Kruszewski SP, et al. Primary care physicians’ knowledge and attitudes regarding prescription opioid abuse and diversion. Clin J Pain. 2016;32:279–284 17. Menendez ME, Mellema JJ, Ring D, et al. Attitudes and self-reported practices of hand surgeons regarding prescription opioid use. Hand. 2015;10(4):789–795. 18. Rodgers J, Cunningham K, Fitzgerald K, et al. Opioid consumption following outpatient upper extremity surgery. J Hand Surg Am. 2012;37:645–650. 19. C, Laciak R, Southwick A, et al. Overprescription of postoperative narcotics: a look at postoperative pain medication delivery, consumption and disposal in urological practice. J Urol. 2011;185(2):551–555. 20. Veliz P, Epstein-Ngo QM, Meier E, et al. Painfully obvious: a longitudinal examination of medical use and misuse of opioid medication among adolescent sports participants. J Adolesc Health. 2014;54:333–340.

Q1 | 2017

23. Revision to Pain Management Standard. Joint Commission Online. 2014. Available at: www.jointcommission.org/assets/1/23/jconline_november_12_14.pdf. 24. Stanek JJ, Renslow MA, Kalliainen LK. The effect of an educational program on opioid prescription patterns in hand surgery: a quality improvement program. J Hand Surg Am. 2015;40(2):341–346. 25. Fearon KC, Ljungqvist O, Von Meyenfeldt M, et al. Enhanced recovery after surgery: a consensus review of clinical care for patients undergoing colonic resection. Clin Nutr. 2005;24(3):466–477. 26. Rice JB, White AG, Birnbaum HG, et al. A model to identify patients at risk for prescription opioid abuse, dependence, and misuse. Pain Med. 2012;13(9):1162–1173. 27. Peng PW, Wijeysundera DN, Li CC. Use of gabapentin for perioperative pain control – a meta-analysis. Pain Res Manag. 2007;12(2):85–92. 28. Doleman B, Read D, Lund JN, et al. Preventative acetaminophen reduces postoperative opioid consumption, vomiting, and pain scores after surgery: systematic review and meta-analysis. Reg Anesth Pain Med. 2015;40(6):706–712. 29. Gupta A, Bah M. NSAIDs in the treatment of postoperative pain. Curr Pain Headache Rep. 2016;20(11):62. 30. Laskowski K, Stirling A, McKay WP, et al. A systematic review of intravenous ketamine for postoperative analgesia. Can J Anaesth. 2011;58(10):911–923. 31. Guay J, Nishimori M, Kopp S. Epidural local anaesthetics versus opioid-based analgesic regimens for postoperative gastrointestinal paralysis, vomiting and pain after abdominal surgery. Cochrane Database Syst Rev. 20Jul 16;7. 32. Andreae MH, Andreae DA. Regional anaesthesia to prevent chronic pain after surgery: a Cochrane systematic review and meta-analysis. Brit J Anaesthes. 2014;1(5):711–720.

www.painweek.org | PWJ

By Jeffrey A. Gudin md

KeY TOPiCS

abstract: The hcahps (Hospital Consumer Assessment

of Healthcare Providers and Systems) survey is the first national, standardized, publicly reported survey of patients’ perspectives of hospital care. hcahps (pronounced “H-caps”) is measured by data collection through a survey instrument in which patients’ opinions of their hospital experience is evaluated. While many hospitals have collected information on patient satisfaction for their own internal use, until hcahps there was no national standard for collecting and publicly reporting information about patient experience of care that allowed valid comparisons to be made across hospitals locally, regionally and nationally. With at least 2 questions focused on pain, it is obvious that pain management will contribute to the overall rating and weight that these surveys carry. The purpose of this article is to define the relatively recent hcahps survey and its role in enhancing not only healthcare accountability, but also transparency of the quality of hospital care. It identifies changes in professional practice and hospital culture that should impact the likelihood that patients will choose the positive “always” when answering pain hcahps survey questions.

Q1 | 2017

www.painweek.org | PWJ

KeY TOPiCS

—Theodore Roosevelt

are no longer paid solely on the quantity of services they provide. The Hospital Value-Based Purchasing (vbp) Program is a Centers for Medicare & Medicaid Services (cms) initiative that rewards acute care hospitals with incentive payments for the quality of care they provide to Medicare beneficiaries. cms rewards hospitals based on the quality of care provided to Medicare patients, how closely best clinical practices are followed, and how well hospitals enhance patients’ experiences of care during hospital stays. the hcahps survey is designed to report data about patients’ perspectives of care to allow objective and meaningful comparisons of hospitals on topics important to consumers. hcahps also promotes public reporting of the survey results and creates incentives for hospitals to improve quality of care. cms and the hcahps Project Team have taken substantial steps to assure that the survey is credible, useful, and practical.1

The survey

hcahps survey is administered to a random sample of adult patients with various medical conditions between 48 hours and 6 weeks after discharge; the survey is not restricted to Medicare beneficiaries. It is 32 questions in length and asks discharged patients questions about their recent hospital stay.2 The survey contains 21 patient perspectives on care and patient rating items that encompass 9 key topics:

PWJ | www.painweek.org

❶ Communication with doctors ❷ Communication with nurses ❸ Responsiveness of hospital staff ❹ Pain management ❺ Communication about medicines ❻ Discharge information ❼ Cleanliness of the hospital environment ❽ Quietness of the hospital environment ❾ Transition of care Q1 | 2017

The survey also includes 4 screener questions and 7 demographic items, which are used for adjusting the mix of patients across hospitals and for analytical purposes. The survey and its protocols for sampling, data collection and coding, and file submission can be found in the current hcahps Quality Assurance Guidelines, which is available on the official hcahps website, www.hcahpsonline.org.

Q1 | 2017

Patients want to know that pain management is a priority to their physicians, nurses, and hospital staff.

The pain management task force

With a competitive landscape, hcahps scores have become increasingly important for hospitals to maintain market share, uphold their reputation and avoid losing reimbursement. The hcahps survey questions requires a patient to answer “always, sometimes, usually, or never” in response to 27 questions about staff communication, quality of service, and the hospital environment. In order for a hospital to obtain a high score, patients need to answer the questions with the “always” response. It is no surprise that since the launch of this survey program, most hospitals have adopted a “culture of always” philosophy.

The pain management team should develop a model to identify the underlying reasons why patients perceive their pain is not well controlled and develop a step-by-step plan for improvement. Our hospital has piloted programs on medical and surgical units, assessed and reassessed and implemented change hospital-wide. Following a needs assessment, we interviewed patients, family members, physicians, nurse managers, and even members of our senior administrative team. A multidisciplinary task force including anesthesiology based pain management physicians, certified pain nurse practitioners, pain nurses, and representatives from pharmacy, pastoral care, and care coordination (social workers) were involved, and a system of accountability and compliance was developed.

The surveys come by mail, telephone and even interactive voice recognition soon after a patient is discharged from the hospital. Survey questions focusing on pain and its management contribute to ratings and the weight of these surveys. No one wants to go to hospital where pain is poorly controlled, and most hospitals recognize that “Good Pain Management = Good hcahps Scores.” Few things are more related to patient satisfaction than relieving pain, but pain management is about more than stopping pain—it’s about building a foundation of trust between patient and caregivers, which ties in to quality of care, level of patient satisfaction, and higher hcahps scores.

This task force discovered a number of interesting findings from the patient perspective: they didn’t want to bother busy staff members or be seen as a “complainer.” Many of the times patients asked for pain medication, they were told it wasn’t time and they had to wait. These issues can usually be addressed in advance by preoperative education. Patients are not told that they will be pain free, but given realistic expectations of pain; use multimodal, opioid sparing pharmacology; and are introduced to complementarity and behavioral modalities such as guided imagery. They are ensured that staff resources are available 24/7 if their pain is not adequately managed. www.painweek.org | PWJ

KeY TOPiCS

Patients who are maintained on chronic opioid analgesics can be a challenge to manage in the perioperative period. At our institution, we attempt to identify these patients prior to admission and arrange for consultation in our outpatient pain center to develop a customized perioperative analgesic regimen. At a minimum, the pain management team sees all patients in the holding area before proceeding to surgery upon same day admission. From a staff standpoint, connecting to the patient or their family is a critical part of satisfaction. Without taking extra time, a practitioner sitting at the patient’s bedside, maintaining eye contact with the patient and family members, and simply asking if there is anything else s/he can do before leaving the room can make the difference between a positive and negative visit. Clinicians must understand the patient’s perspective and expectations and work cohesively to develop pain management goals. Like Teddy Roosevelt was quoted saying, “People don’t care how much you know until they know how much you care.”

Hospital based pain management teams need to recognize that the goal is not to focus on these scores, but to improve staff knowledge and quality of care. There is an important and well documented link between employee/clinician satisfaction and patient satisfaction. Changing hospital culture and improving the quality of care will naturally improve hcahps scores. References 1. Centers for Medicare & Medicaid Services. hcahps: Patients’ perspectives of care survey. hcahps overview. Available at: www.cms.gov/Medicare/Quality-Initiatives-Patient-Assessment-instruments/HospitalQualityInits/Hospitalhcahps. html. 2. hcahps hospital survey. About the survey. Available at: http://www.hcahps online.org/home.aspx#aboutsurv. 3. Hospital Value-Based Purchasing (VBP) Program Update: Section 1886(o). Available at: https://www.federalregister.gov/documents/2016/11/14/ 2016–26515/medicare-program-hospital-outpatient-prospective-paymentand-ambulatory-surgical-center-payment.

Other initiatives include a whiteboard as a visual reminder of a patient’s pain goals and treatments, reinforcing the message that we are “always” going to try to control their pain. Tent cards with pain education, nonpharmacological recommendations (ie, ice, positioning) relaxation techniques, and a rescue system with telephone numbers of who to call made a difference as well. High hcahps performing sites credited their success not to specific practices, but to a well-established culture of patient centered care. These sites had implemented a comprehensive approach to family involvement, and patient and staff engagement. Remember the aidet fundamentals of communication: acknowledge, introduce, duration, explanation, and thank you. Some clinicians have reported feeling pressure to overprescribe opioids because scores on the hcahps survey pain management questions are tied to hospital Medicare payments. In an effort to combat the opioid addiction in the United States, cms proposed in July of 2016 removing pain management-related questions on the hcahps survey from the hospital payment scoring calculation. Under the proposal, the pain management questions on the hcahps survey would no longer factor into the Hospital Value-Based Purchasing Program payments from Medicare, starting in fiscal year 2018. The questions would remain on the survey, however.3

Conclusion

Publicly reported hcahps scores are vital markers of hospital performance and reimbursement. Patients’ experiences and results of these surveys are heavily influenced by both hospital clinicians and employees. Hospitals that use a structured approach to performance management are more likely to have positive patient experiences and higher survey scores.

38 PWJ | www.painweek.org

Q1 | 2017

CONFeReNCe PReVieW

2017

Sept. 5â&#x20AC;&#x201C;9

The Cosmopolitan of Las Vegas

conference preview

“

PAINWeek is an excellent conference for frontline practitioners because the level of discussion is definitely at the cutting edge of science. There is so much good information that it’s not even possible to get everything in one fell swoop; it will require coming back again!” —Jennifer Hah md, ms

Launched in 2007, PAINWeek quickly ascended to become the largest US pain conference. In 2017, we invite you to celebrate and participate in a decade of unparalleled leadership that has elevated the pain management acumen of approximately 12,000 healthcare providers over the last 10 years. Celebrating our 11th year, PAINWeek remains the favorite destination for frontline practitioners to enhance their competence in pain management. Join us for a comprehensive program of a multidisciplinary curriculum, satellite events, and exhibits. To learn more and register for PAINWeek 2017, visit www.painweek.org, and follow us on Twitter® at twitter.com/painweek.

WORKSHOPS A Comedy of Errors: Methadone, Marijuana, and Buprenorphine Presented Tuesday, Sept 5 9:00a – 12:00p Registration Fee: $165 The 3 most contentious, poorly understood analgesics today are methadone, cannabis, and buprenorphine. This fast-paced workshop will equip practitioners with immediately implementable practical tips regarding when and how to use these analgesics, including dosage formulations, routes of delivery, appropriate use in therapy, drug interactions, dosage titration (up and down), opioid conversion calculations, and more. All discussions will be aimed at enhancing clinical, economic, and humanistic outcomes on the individual patient and health system level.

Managing Pain Between a Rock and a Hard Place:

Getting the Tough Jobs Done in Serious Illness Presented Tuesday, Sept 5 1:40p – 4:40p Registration Fee: $165

Patients with serious illnesses often experience painful clinical situations that are beyond the scope of usual and customary practice. Palliative care practitioners are skilled at thinking “out of the box” to get the job done, including recognizing and treating opioid induced hyperalgesia, pain in highly opioid tolerant patients, and the use of analgesics such as ketamine (by a variety of routes of administration), methadone (oral and parenteral), and lidocaine (parenteral and topical). Participants in this interactive workshop will leave with practical strategies to treat difficult pain syndromes in advanced illness, including painful wound care.

Winning the Game of Groans:

Strategies and Tactics for Preserving the Pain Practitioner’s Decision to Prescribe Controlled Medication Presented Wednesday, Sept 6 9:00a – 12:00p Registration Fee: $185 Back by popular demand, this hands-on workshop—a huge success at last year’s conference—will instruct pain practitioners on key self-audit strategies and tactics to demonstrate and document patient evaluation and monitoring when prescribing controlled medications to treat pain. Using a combination of teaching methods, faculty will present not only the “what” of quality patient evaluation and monitoring, but also the “how to” of compliance and documentation strategies. Faculty and learners will work through extensive case examples and various treatment puzzles to accomplish course objectives.

PARTiCiPATiNG ORGANIZATiONS American Headache Society (ahs) Presented Tuesday, Sept 5

Developed by the American Headache Society®, the Chronic Migraine Education Program (cmep) includes new advances and addresses acute and preventive treatment options. In addition, the cmep highlights epidemiologic data on the scope and distribution of migraine with an emphasis on diagnosing chronic migraine,

and recent insights into the mechanisms of the disorder setting the stage for improving treatment outcomes for this most disabling of headache disorders. Part 1 will cover Diagnosis of Chronic Migraine, risk factors, and prognosis. Part 2 will cover Preventive Pharmacotherapy for chronic migraine and advances in acute treatment.

American Pain Society (aps) Presented Friday, Sept 8

The theme of this year’s aps Track is Bend Don’t Break: Building Resilience Against Chronic Pain. Previous pain research emphasized identifying risk factors and pathological states. While of obvious importance, this pathology based approach neglects the importance of identifying resilience factors that protect against pain or enable individuals to respond adaptively in the face of pain. The aps Track at PAINWeek 2017 will feature 5 sessions. The first is Resilience vs Vulnerability in Chronic Pain. Next, The Biological Interface of Resilience will discuss how resilience factors may prevent the adverse biological outcomes of chronic pain. Ramping-Up Resilience for Chronic Pain: Strategies for Reducing Pain and Improving Function will emphasize novel interventions that may increase resilience. Resilience Interventions for Pain will feature multidimensional interventions to promote resilience in people with fibromyalgia. The final session is Building Brain Resilience through Mindfulness Meditation.

American Society of Pain Educators (aspe) Presented Wednesday, Sept 6 and Thursday, Sept 7

The 12th annual Pain Educators Forum will present 2 days of clinical and adult learning courses. Day 1 features Pain Terminology, which addresses how “knowing the difference makes a difference,” followed by Pain Pathophysiology Unraveled, uncovering the underlying mechanisms responsible for pain. Chronic Pain Assessment offers effective communication and evaluates screening tools. Next, Pain Diagnostics: Clinical Pearls to Improve Common Tests for Pain speaks to the importance of diagnostic testing for differential diagnosis (and their inherent limitations), followed by an extensive presentation on Pain Therapeutics. Day 2 presents Flipping the Script: Why We Need a Patient REMS Course; You’re Giving me an mi: Incorporating Motivational Interviewing into Challenging Conversations; and Who Gives a Hoot about Pedagogy, Andragogy, and Heutagogy? How Educators Can Help Learners Learn.

International Pelvic Pain Society (ipps) Presented Thursday, Sept 7

The International Pelvic Pain Society (ipps) joins PAINWeek for the first time, presenting What’s Going on Down There? Demystifying Female Pelvic Pain Syndromes. First is Don’t Dismiss Dysmenorrhea: A Systematic Approach to the Evaluation and Management of Painful Periods. Early and prompt treatment of dysmenorrhea may be an important target for prevention of central sensitization, as well as the progression to various chronic pain conditions. When Pain Is Not Sexy: Evaluation and Management of Sexual Pain in Females reveals how sexual pain fits the biopsychosocial model of pain. Pelvis Gone Wild: A Sordid Tale of Musculoskeletal Dysfunction will discuss pelvic pain conditions (endometriosis, vulvodynia, painful bladder syndrome, etc) and key abdomino-pelvic musculature. The final course, To Infinity and Beyond Pharmacotherapy: An Integrative

www.painweek.org

Note: Courses and tracks are subject to change.

Approach to the Management of Female Chronic Pelvic Pain, will discuss varied integrative modalities—conventional and plantbased medicines, nutrition, movement therapies, manual bodywork, etc. Throughout the track, faculty will utilize clinical vignettes and video demonstrations.

National Association of Drug Diversion Investigators (naddi) Presented Thursday, Sept 7

The 2017 naddi Track will bring current trending information with a primary focus on drug diversion nuances. Topics will include Data Fiction—Do We Make Life and Death Decisions Based on Bad Data? and the problem it poses for the healthcare industry; Algorithms and Opioid Dosing Watch Lists and how they are used in investigations; the status of the many national Overdose Prevention Strategies and whether they are working; Opioid Counterfeits that are on the black market and the fallout on our streets; and also insight into a Pain Practice Check-Up and how law enforcement uses deviations from Standards of Practice as probable cause for search warrants.

FeATUReD TRACKS

NeW! Functional Medicine

Presented Tuesday, Sept 5 All You Need is Love: Incorporating Functional Medicine in Pain Care will teach providers about the development and implementation of an intervention that addresses the 4 key pillars of an anti-inflammatory lifestyle. In addition, there will be some exploration of how a person expresses love and feels loved, the ultimate measure of a patient’s well-being and health. Food is Medicine: A Review of the AntiInflammatory Diet will guide providers on how to implement a modified elimination diet. Use of this diet necessitates the removal of the most common causes of food reactions while monitoring clinical symptoms to see if there is an improvement in how the patient feels. During this presentation the facilitators will outline what foods to eliminate/ adjust. Looking in the Rear View Mirror: Addressing Inflammation Through Lifestyle Imbalances will guide providers on how to coach patients to change their environment and live an anti-inflammatory lifestyle by focusing on proper sleep hygiene, stress management, and how to adjust an exercise program to accommodate the individual needs and capabilities of the patient. The goal of the intervention is to educate and support self-care among chronic pain patients, not just during treatment, but for a lifetime.

NeW! Medical Cannabinoids and Medical Marijuana

Advanced Practice Provider (app) Presented Thursday, Sept 7

Presented Friday, Sept 8

Returning this year is the acclaimed Advanced Practice Provider (app) Track, focusing on practice issues surrounding pain education and management, most pertinent to nurse practitioners, physician assistants, clinical nurse specialists, and other frontline clinicians. The track, created and presented by apps for apps, will provide a full-day of diverse educational offerings, beginning with a 2-hour Case Based Learning presentation from the perspective of an interdisciplinary panel, reviewing complex case studies on common, but otherwise challenging-to-manage pain syndromes, including chronic low back pain, postherpetic neuralgia, and diabetic peripheral neuropathy. The final 3 hours of the day will be broken up into 3 separate 50 minute courses, the first of which will exam The Importance of Chart Documentation: Through the Eyes of a Chart Reviewer. Specifically, the balance of all factors associated with safe opioid prescribing will be described. Pitfalls associated with use of an ehr when caring for the chronic pain patient will be explained, along with identification of essential items that should be included in your documentation when caring for the patient with chronic pain. Blending, Melting, or Throwing Off a Cliff? Abuse Deterrent Technologies to Minimize Opioid Abuse will focus on the fda’s publication “Abuse Deterrent Opioids—Evaluation and Labeling: Guidance for Industry,” as well as discuss many of the novel technologies developed and labeled specifically to minimize the likelihood of abuse, while retaining the potential benefits of opioids in the management of pain. The Green-Eyed Martian: Do Healthcare Disparities Exist in Pain Management?, the final lecture, will explore the topic of disparities in pain management. It will define the epidemiological findings that define the scope of the problem related to disparities in pain management about race, ethnicity, and socioeconomic status. Case scenarios will be presented representing life examples. Finally, strategies to minimize disparities in healthcare when it comes to providing pain management will be identified.

The past several years have witnessed dramatic increases in the use and state-mandated legalization of medical cannabinoids, as well as a growing number of states that have legalized marijuana recreationally. Reefer Madness: Taking the Insanity Out of Medical Cannabinoids will serve as an update of what we know and what we don’t know about the safety and efficacy of medical cannabinoids for pain management. Different perspectives will be presented in this track, among them Cannabis vs Cannabinoids: The Politics of Medical Marijuana, which will discuss the tendency to equate medical cannabinoids with medical marijuana, and the distinctions between the 2 will be explored. Medical Efficacy of Cannabis Therapeutics: Focus on Pain Management will cover misinformation and lack of understanding by hcps about cannabinoids. Specifically, this course will address the discovery of the endocannabinoid system (ecs) as a modulator of nociception and the role that phytocannabinoids have on the ecs. With more acceptance and use of cannabis for a variety of medical conditions, typically pain, there comes health and societal effects, many of which have been unanticipated. Cannabis and Pain: Lessons From Colorado looks at growing pains experienced along the way, particularly with de facto legalization prior to the vote to legalize.

NeW! Physical Therapy

Presented Tuesday, Sept 5 Words Wisely Chosen: Avoiding the Unintended Nocebo Effect will teach clinicians to explain body pain in terms of anatomy and biomechanics. Alternative, descriptive terms/phrases to use during patient interactions will be offered. Exercise Prescription for Patients With Chronic Pain will discuss low exercise compliance and review guidelines and trials discussing implementation of patient coaching techniques to bridge the gap between evidence and practice to help

www.painweek.org

Note: Courses and tracks are subject to change.

patients attain better function and a healthier lifestyle. At the Edge of Interaction: Applying Edge Work and Novel Movement to Painful Motion is well-suited for clinicians working or interested in fields of movement therapy, manual therapy, physical medicine, and rehabilitation as it relates to pain. Restoring Hope: The Treatment of Pelvic Pain Across the Gender Spectrum will outline interdisciplinary options to identify persons with pelvic pain and design treatment programs to restore optimal function. Lastly, the Fascial Distortion Model (FDm) gives practitioners the ability to interpret a patient’s pain complaints and direct treatment to correct fascial distortions.

NeW! Wound Care

Presented Saturday, Sept 9 This new track discusses the necessity of wound care. Each of the 2-hour sessions will inform attendees of the importance of proper care of the body’s largest organ: skin. Woundology—The Spectrum of Reasons Why the Epithelium Gets Lost reviews the major causes of wounds that may present in a practitioner’s office. The presenter will offer common sense ways to make the diagnosis and decide if treatment can be performed in the office or should be referred to a specialist. This session will provide an overview of the basic pathophysiology of several common types of wounds and sets the stage for the second session, Insult to Injury: Wound and Other Pains in a Wound Care Patient. Once a diagnosis of the etiology of a wound or related condition has been made, treatment of the pain associated with it needs to be logical, successful, and multifocal to address not just the pain but related and interrelated causes. This presentation will look at the causes of pain related to various wound conditions and discuss treatment options as well as overall pain control.

SPeCiAL iNTeReST SeSSiONS Measure for Measure:

Prescribing Guidelines, Rules, and Regulations The state of Washington was one of the first states to legislate prescribing rules for the treatment of chronic pain, a unique model that relied on the use of a dosage trigger and the necessity to calculate morphine equivalency. Following Washington’s lead, the Centers for Disease Control and Prevention (cdc) as well as other states have created their own guidelines and rules that not only vary widely but are often in conflict with each other. This presentation will discuss the recent history of prescribing guidelines, their diffusion across the United States, and their potential impact on medical practice and the treatment of pain.

Walking the Tightrope: Pain, Addiction, and Suicide Death by suicide has become a global epidemic. Every 40 seconds someone in the world dies of suicide. An estimated 804,000 suicide deaths occurred worldwide in 2012. Individuals with chronic pain commonly have significant concomitant psychiatric and medical disorders placing them at higher risk for suicide. This presentation will review current literature on the epidemiology of suicidal ideation in the pain and substance use disorder populations, and discuss assessing suicide risk and identifying modifiable mediators of pain, substance use disorder, and suicide.

As You Like It: The Business of Pain Medicine It has been estimated that approximately 30% of adults in the United States suffer from chronic or recurrent pain and this number grows annually. Pain care models have in the past evolved from unimodal/ multimodal approaches to cost effective, efficacious interdisciplinary care. Over the past few years the field of pain medicine has regressed from providing a more holistic, interdisciplinary approach to emphasizing unimodal (spinal injections, spinal cord stimulation), and at best limited multimodal (medication management, procedures) interventions. The long-term efficacy and costs of these currently standard treatments varies greatly. This presentation will provide a critical review of good vs poor evidence based pain medicine interventions and the associated costs to patients and society.

Are You Now… or Have You Ever Been? Saving Pain Medicine from Zealotry

Healthcare providers continue to incur the ire of anti-opioid zealots who have engaged in marginalization of prescribers and the millions of people who take opioids responsibly. This panel discussion will explore the many policy and ethical issues surrounding the prescribing of opioids and provide prescribers with some strategies that may help effect change and improve the lives of the people they treat.

The Story of O—A Molecule in Chains? The management of chronic pain syndromes with long-term opioid therapy remains controversial. How are clinicians supposed to responsibly sift through the miasma of evidence based data, and the chorus of cnn, cdc, and dea voices, while helping patients manage their chronic pain? This presentation separates fact from fiction, acknowledges the dilemma facing healthcare providers today, and provides practical insight to frontline practitioners grappling with this quandary.

Using Electronic Pain Assessment Programs and Innovative Technology in Pain Medicine:

Where Are We Now and Where Are We Going?

There has been a rise in interest in remotely assessing and monitoring pain and associated symptoms (eg, fatigue) as well as in the use of electronic health (eHealth) technology designed to support individuals in making lifestyle changes needed to improve pain management. Consumer demand for remote assessment programs, health ‘apps,’ and sensors has far outpaced the science needed to understand their benefits and impact. For persons with chronic pain and the providers who treat them, assessment programs, mobile apps, and activity monitors can help encourage behavioral change, including symptom monitoring, and serve as useful tools to enhance patient-provider communication. This 90-minute session will detail the content, and face validity, reliability, usability, benefits, barriers, and technical issues associated with the use of eHealth technology for persons with chronic pain and discuss future areas for clinical use. Note: Confirmed dates/times for all Special Interest Sessions will be noted in the forthcoming Schedule-at-a-Glance, available May 2017.

www.painweek.org

Note: Courses and tracks are subject to change.

Planning Your PAINWeek Experience For those who would like to have an idea of what days will feature specific tracks, the following, while subject to change, is a fairly accurate representation of the 120+ hours presented over the 5 day conference. Tues 9.5

Wed 9.6

American Headache Society Track: ahs

Thurs 9.7

Fri 9.8

Sat 9.9

Acute Pain Management Advanced Practice Track: acu Provider Track: aap

American Pain Society Track: aps

Integrative Pain Management Track: intg

Behavioral Pain Management Track: bhv

Chronic Pain Syndromes Track: cps

International Pelvic Pain Society Track: ipps

Medical/Legal Track: mdl

Pain and Chemical Dependency Track: pcd

NeW! Functional Medicine Track: fpm

Interventional Pain Management Track: int

National Association of Drug Diversion Investigators Track: nad

NeW! Medical Cannabinoids and Medical Marijuana Track: mcb

Palliative Care Track: pal

Health Coaching Track: hch

Pain Educators Forum Track: pef

Neurology Track: nro

NeW! Wound Care Track: wou

NeW! Physical Therapy Track: pth

Medical/Legal Track: mdl

Pharmacotherapy Track: phm

Master Class Track: mas

Special Interest Sessions Track: sis

Keynote/Exhibit Hall Opening Reception

Scientific Poster Session/Reception

Exhibit Hall Closing Reception

Registration is $649* ■ HOT eL iNFORMATiON

The Cosmopolitan of Las Vegas

3708 S Las Vegas Boulevard, Las Vegas, NV 89109 Conference rate $165 + tax per night. This rate is applicable to healthcare providers only, and can only be guaranteed if reserved by July 29, 2017. Please note: You will receive hotel booking information upon completion of your conference registration.

■ R eGiSTRATiON OPTiONS Visit www.painweek.org Fax the registration form to (973) 741–2337 Call toll free (877) 724–6933 Mail (make a copy for your records) to: PAINWeek, Attn: Patrick Kelly, 6 Erie Street, Montclair, NJ 07042

Look for additional information at

*Registration fee is valid until 5.31 and is for practicing HCPs only. Full conference price is $859.

5 Days, 120+ Hours, and 90+ Faculty In 2017, you can look forward to a week of Special Interest Sessions, Master Classes, and multidisciplinary course concentrations.

PW17 CPREViEW 2.14.indd 7

3/20/17 5:34 PM

CL iNiCa L CONUNDRUM

A situation in which there are only 2 possibilities and you cannot do either because each depends on having done the other first; a problematic situation for which the only solution is denied by a circumstance inherent in the problem or by a rule. As physicians, we are all accustomed to dealing with difficulties with patient diagnosis and treatment secondary to a Catch-22— an unaccountable reason that makes no sense, but nevertheless prevents us from doing what we need to do.

By Gary W. Jay md, faapm, facfei

CLiNiCaL CONUNDRUM

“

As physicians, we are all accustomed to dealing with difficulties with patient diagnosis and treatment…

“

The patient in question was seen in the 1980s: a 35-year-old, right handed Caucasian woman with a history of neurologic abnormalities occurring for 2 months. She had been diagnosed with transient ischemic attacks (tias). At issue, there was no diagnosis as to the cause, or even if the attacks were real. On reviewing her old records, I read that several physicians had written in their charts that the patient was “faking.” The patient was sent to see me secondary to complaints of a constant headache. I took a history, during which the patient and her husband described about a dozen instances of transient neurological episodes over the prior 2 months, including, by patient description, aphasia, hemiplegia, paraplegia, unilateral blindness, and more, the duration of the typical episode ranging from hours to 2 days. The patient’s husband of 6 months was solicitous of his wife, perhaps too exceptionally solicitous. Questions of secondary gain were on my mind.

48 PWJ | www.painweek.org

Q1 | 2017

After her history was obtained, the patient was taken by my nurse to the examination room, along with her husband, and asked to change into an exam gown. I started the neurological examination: she had normal cranial nerves, and gait and station were intact. I began the muscle testing examination and as I was examining her upper extremity strength, her left upper extremity became weak as I was testing the biceps/triceps. She appeared to develop a paresis, not a total hemiplegia. I did what I could to see if the patient was faking, but I could not determine that she was. Both she and her husband were, of course, aware of the paresis. At the end of the examination, after they were back in my consultation room, I retested her left upper extremity strength, and it remained weaker than the right. I asked the patient (again) how long such changes typically lasted, to see if she gave me the same answers she gave me earlier, and she said they ranged, “from hours up to 2 days.” In terms of her primary problem, her headaches, there was some evidence of bilateral trapezius and deltoid spasm with tender trigger points, but when the patient’s arm became weak, it placed that part of the examination in a different context. Spasm could be secondary to “holding up” the weak limb but, bottom line, I could make no definitive headache diagnosis at that time. Q1 | 2017

I told the patient that I thought it would be a good idea to place her in the hospital and work her up. The patient and her husband didn’t want that. However, I insisted: if they wanted me to continue seeing her, she needed to be in the hospital. The patient was hospitalized, and among my initial orders was a cerebral cat scan. Some orientation: this patient was seen in the early 80s. There were no mri scans in hospitals. A cat scan had just recently been placed in the hospital at which I was on staff, about 2 years prior. I ordered the cerebral cat scan. There was, however, a major problem: her insurance!!! (Who’da thunk it?) Basically, cat scans were new and expensive in 1983, and my patient needed a cat scan. Unfortunately, her www.painweek.org | PWJ

CLiNiCaL CONUNDRUM

The patient couldn’t have a CAT scan as she hadn’t had one before; ie, she need a prior CAT scan before her insurance would pay for her to have a follow-up CAT scan.

insurance stated that she couldn’t have one unless she had had one before and the desired cat scan was a follow-up. I called them and went around and round: the issue was ridiculous but they were adamant, because, again, the tests were very expensive and very new. The patient and her husband could not afford to pay for one themselves. I wanted the patient in the hospital so at least I could follow her while I continued to deal with her insurance and consider other studies. While the patient and her husband were in my office I called the insurance company again, to speak with their Medical Director. He couldn’t talk to me for 2 days. The insurance carrier had no issue with my hospitalizing the patient, just with paying for the test she needed. Again: The patient couldn’t have a cat scan as she hadn’t had one before; ie, she need a prior cat scan before her insurance would pay for her to have a follow-up cat scan.

Catch-22! The patient’s left upper extremity weakness was gone by 8:00 that night. The next morning, the patient awakened with a left homonymous hemianopsia: an absence of vision towards one side of the visual world in each eye. I called the insurance company again and raised hell, again to no avail. The Medical Director wouldn’t be back until the next day.

50 PWJ | www.painweek.org

There was another way to do what I wanted, which after consideration would be more telling. I met with the Chairman of the Department of Neuro-Radiology and told him that I wanted my patient to have a cerebral angiogram. He said, “No,” that possible complications could occur, and a cat scan would be better. I explained the problem I was having with the patient’s insurance. He told me to wait and talk to the Medical Director of the insurance company and that he was “sure that we could work it out.” That midafternoon, I was seeing patients in my office and received a call from the floor nurse taking care of this patient. Her hemianopsia had gone away, but she was now hemiplegic on the right side. I went immmediatly to the hospital to examine the patient myself. Either she was the world’s best medical actress or she did indeed have a right hemiplegia. That was the third transient neurological event (if the hemiplegia was going to be transient, which the patient stated it would be) since I had met her: a paresis, a hemianopsia, and now hemiplegia. I had to find the underlying cause of things before something permanent happened to her. I went back to speak to the Chairman of Neuro-Radiology, who repeated that he would not do a cerebral angiogram. I then told him I thought there was something going on that we could only find via angiography. He essentially told me that I hadn’t a clue what I was talking about. I told him that he needed to do the test and if he Q1 | 2017

wouldn’t, and the patient ended up with a cerebrovascular accident, I would see him at the next monthly Hospital Department meeting and I would not be happy. I knew I was acting like an idiot. I was a relatively new physician and I was pressuring an older physician who was the Chairman of his department. If I was wrong, and the patient didn’t have what I thought she did, diagnostically, I would be in a position of making enemies and probably getting thrown off staff—NOT a good thing to do. The physician, begrudgingly (to say the least), finally agreed to do the cerebral angiogram. I was in attendance at the test. Multiple neurological issues within a short period of time from different parts of the central nervous system made me want to look for a vasculitis. During my residency, we had a cat scanner where I trained, but I had never seen a vasculitis diagnosed by cat scan. The angiogram was better.

So, the diagnosis was…??? Primary Angiitis (Vasculitis) of the Central Nervous System, or pacns1 In a review of 68 patients with a pathological diagnosis from different series, the most common symptoms of pacns presentation were nonfocal, such as headache (58%) and altered mental status (47%).2 Localizing symptoms frequently seen on presentation were lateralized weakness (32%), aphasia (14%), and nonspecific visual complaints (17%). Seizures were among the presenting symptoms in about 15% of patients.2 The earliest reports of pacns described the disease as fatal and progressive, limited to the cns, and characterized by rich granulomatous vasculitis. The disease was named granulomatous angiitis of the cns (gacns). A primary vasculitis limited to the cns is referred to as a primary angiitis of the cns (pacns). A generalized systemic vasculitic process can also involve the cns and in such cases, it is referred to as secondary vasculitis of the cns. pacns was first described in the mid-1950s. An increasing number of cases had been described by 1975, but by 1986, only 46 cases had been reported in the English-language medical literature. Over 500 cases were reported through 2007. pacns affects patients of all ages, but peaks around 50 years of age and is most common in men. A retrospective analysis of 101 cases revealed that the average annual incidence of pacns was 2.4 cases per 1 million person-years. Today, although pacns is still uncommon, its specter is often raised in patients with Q1 | 2017

neurological problems of obscure origin, making its diagnostic approach a relevant clinical issue.3 The initial event that primes the inflammatory cells is not known. However, the final pathway of inflammation leads to occlusion of the involved blood vessel, thrombosis, and ultimately ischemia and necrosis of the territories of the involved vessels. Limited data suggest an association with systemic viral illnesses or a state of altered host defense and pacns. Duna and colleagues analyzed 168 reported cases of pacns and found that 29 of these were associated with an illness characterized by an immunosuppressive state.4,5 The course of the illness is also variable with presentations ranging from hyperacute to chronic and insidious. In patients with the disease variant gacns, characterized by a presentation of chronic meningitis and a small-vessel distribution, signs or symptoms might precede diagnosis by 3 years or more.3,6 The most common symptoms of pacns are headaches followed by neurological deficits. The headache varies in description, intensity, and pattern; it is usually chronic and insidious. Other symptoms include cognitive impairment, stroke, and tias occurring in 30% to 50% of patients. Strokes are usually multiple and vary in age. Cranial nerves can be affected, in addition to causing myelopathy, seizures, and ataxia.3,6 Clinical features of pacns include: ● Headaches ● Encephalopathy ● Strokes/transient ischemic attacks ● Seizures ● Behavior changes ● Focal motor/sensory abnormalities ● Ataxia ● Cranial neuropathies ● Visual changes ● Myelopathy ● Radiculopathy The most common scenarios where pacns is considered include: ❶ Multiple episodes of cerebral ischemia, affecting different vascular territories in association with an inflammatory pattern in the cerebrospinal fluid ❷ Subacute or chronic headache with cognitive impairment or chronic aseptic meningitis ❸ Chronic meningitis presentation after infectious and neuroplastic disorders have been ruled out The patient in question had only number 1

www.painweek.org | PWJ

CLiNiCaL CONUNDRUM

The diagnosis of cns vasculitis is secured by either a positive biopsy or high-probability vascular imaging such as angiography, while excluding other conditions that can mimic the disease7 such as: ● Systemic vasculitides and connective tissue diseases, such as polyarteritis nodosa ● Allergic granulomatosis ● Vasculitis with connective tissue disease ● Henoch-Schonlein purpura ● Granulomatosis with polyangiitis (Wegener’s) ● Temporal and Takayasu’s arteritis ● Behçet’s syndrome ● Systemic lupus erythematosus ● Sarcoidosis ● Lymphomatoid granulomatosis Cases with granulomatous pathologic findings have a progressive and highly lethal course. These patients are treated with a combination regimen of cyclophosphamide and glucocorticoids.7

Back to our patient After the cerebral angiogram, I went to see my patient, who was now diagnosed with probable pacns. As I got to the door of her room, I heard the physician who did the angiogram tell her that I had essentially forced him to do the test. Now that we knew the actual diagnosis, he said he doubted we would’ve discovered it on a cat scan. He told her I was a “good doc.” As I entered the room, he shook my hand and left.

and neuropathology is optimal. Reversible cerebral vasoconstriction syndrome represents a major mimic of pacns.7 The patient in this article was lost to follow-up. I never saw her again, nor did the immunologist. I never did speak to the Medical Director of her insurance company. This was a case, however, in which the Catch-22 actually helped the person who was caught in it. References 1. Hajj-Ali RA, Ghamande S, Calabrese LH, et al. Central nervous system vasculitis in the intensive care unit. Crit Care Clin. 2002;18:897–914. 2. Younger DS. Vasculitis of the nervous system. Curr Opin Neurol. 2004;17(3):317–336. 3. Salvarani C, Brown RD Jr, Calamia KT, et al. Primary central nervous system vasculitis: analysis of 101 patients. Ann Neurol. 2007;62(5):442–451. 4. Duna GF, George T, Rybicki L, et al. Primary angiitis of the central nervous system: an analysis of unusual presentations. Arthritis Rheum. 1995;38(suppl 9):S340 (abstract). 5. Calabrese LH. Vasculitis of the central nervous system. Rheum Dis Clin North Amer. 1995;21(4):1059–1076. 6. Calabrese LH, Duna GE, Lie JT. Vasculitis in the central nervous system. Arthritis Rheum. 1997;40(7):1189–1201. 7. Hajj-Ali RA, Calabrese LH. Primary angiitis of the central nervous system. Cleveland Clinic Center for Continuing Education. July 2015.

I started the patient on IV glucocorticoids and consulted an immunologist. It was via a thorough workup instituted by the immunologist that we excluded every other diagnosis. I asked the immunologist to take care of her treatment while I followed along closely. He started her on several drugs in addition to the glucocorticoids I had started. She left the hospital after 2 weeks on oral medications. She was headache free.

Conclusion A primary vasculitis limited to the cns is referred to as primary angiitis of the cns—pacns—and is one of the most difficult diagnostic and therapeutic challenges to physicians. Correct diagnosis requires a high degree of suspicion along with knowledge of other diseases that can masquerade as pacns. It is a rare disorder but has been increasingly recognized in recent years. Prompt diagnosis either by biopsy of cns tissue or by an organized team with expertise in neurovascular disease, immunology or rheumatology, neuroradiology,

PWJ | www.painweek.org

Q1 | 2017

SHORT CUTS

David Cosio phd Psychologist Jesse Brown va Medical Center

I see my role as an educator, not only to patients who suffer from chronic pain, but also to providers who work with the chronic pain population.”

GPS Chicago, Illinois Typical Day “As a psychologist working in a pain clinic, I see my role is to help patients learn better ways to manage stress or other difficult emotions connected to pain, and to help them create a better multidisciplinary self-management plan to address pain.” Persona “I see my role as an educator, not only to patients who suffer from chronic pain, but also to providers who work with the chronic pain population.” Social Media Habits “I tend to check Facebook® and Twitter®. I have my own accounts on both and am able to connect and communicate with other professionals in the field using those social media outlets.” Politics “I have grown to admire Bernie Sanders and Elizabeth Warren as public figures since the last election. Their approach to politics is similar to the approach I like to take when working with patients with chronic pain. I view chronic pain management to be not only a personal, but a social and public health concern. Together, we can help one another, and it is only when we love each other that we see true change.” Words “I think the book Managing Pain Before It Manages You by Margaret A. Caudill, md, phd, mph, should be required reading for anyone suffering from chronic pain or as a beginner’s guide for anyone beginning to work in the field of pain management.” Popcorn “There are so many great, inspirational films out there. The one that comes to mind is Pay It Forward with Haley Joel Osment. I love how the film underlines how the actions of one person can have a large impact on those around him/her. It speaks to how we as providers can make a small change in our work that can then have a larger impact on the public.” PAINWeek “I have been going to PAINWeek since 2009. Once I experienced the conference the first time…I was hooked! I thoroughly enjoy networking with professionals from all over the country and have learned best practices from several different disciplines. I always go back to work with several new good ideas or at the very least with improvements to old ones.” Q1 | 2017

www.painweek.org | PWJ

SHORT CUTS

By Doug Gourlay md, msc, frcpc, fasam

“What do I do with an abnormal urine drug screen?” First, contact the lab to be sure the result is, in fact, abnormal. Absence of a prescribed medication may indicate a problem but “borrowing from tomorrow to pay for today” is a much more likely reason for negative drug screens than diversion of drugs. Regardless, the result should have a consequence. Bring the patient in to discuss the result: “I need help interpreting your udt results.” Patients react better when approached in a positive fashion rather than a practitioner taking an adversarial approach. While there are many possible “correct” responses to an abnormal udt result, there is only one absolutely incorrect response: “Do nothing.” Ignoring evidence of aberrant behavior will almost certainly cause harm to you and your patient.

54 PWJ | www.painweek.org

Q1 | 2017

SHORT CUTS

Data from

1,226 participants found that the 36 individuals with the most risk factors for heart disease were

4.6×

more likely to have had shoulder joint pain and

6×

as likely to have rotator cuff tendinopathy as those with no risk factors. Participants with some of the risk factors were

1.5× 3× and

as likely as the risk-free cohort to have experienced these issues.1

15,264

patients who underwent total joint replacement between 2000 and 2014,

9% 34% 57% were smokers,

were former smokers, and

were nonsmokers.

The active smokers recorded an

80% higher rate

A study

in Finland correlated serum vitamin D levels and headache incidence in

2,600 men aged 42 to 62.

68%

had serum levels below the accepted 50 nmol/l minimum, and

250

of these reported at least 1 chronic headache per week. Additional work is needed to establish the efficacy of vitamin D supplementation as prophylaxis or treatment for headache.2

of postsurgical infection requiring reoperation within 90 days of their procedure. The study is the largest to date to examine smoking as a risk factor for septic complication from arthroplasty.3

89 patients

with generalized anxiety disorder were randomized to 2 groups, 1 of which received an

8-week course in mindfulness meditation, and the 2nd, a different course in stress management. The cohort exposed to mindfulness meditation recorded significant drops in biomarkers for stress, compared to the group who did not. The study represents the first controlled clinical trial of its type, according to the authors.4

A 12-year survey of over

19,000 patients

age 51 or older reports that the poorest, least educated cohort were

80%

more likely than the wealthiest, best-educated subset to report chronic pain, and

370%

more likely to suffer pain severe enough to result in disability. Study subjects in their 60s in 2010 also reported more pain than did the same age group in 1998. The study highlights sociodemographic risk factors for chronic pain that clinicians should be aware of.5

A stem cell bandage was implanted in 5 patients aged 18 to 45 with white zone meniscal tears.

All

had

an intact meniscus at 12 months postprocedure,

and

retained

the improvement at 24 months. The new approach may benefit the over

1 million people

who suffer meniscal tears each year,

90%

of which are now difficult to repair without inducing risk of later life osteoporosis.6

1. http://bit.ly/2lSWiIT 2. http://bit.ly/2kWHESt 3. http://bit.ly/2l1K0iB 4. http://bit.ly/2kCnQQQ 5. http://bit.ly/2lm6Dzk 6. http://bit.ly/2lbHM

Q1 | 2017

www.painweek.org | PWJ

SHORT CUTS

Meditation More Powerful than Medication?

Sean Fargo

It’s pretty remarkable that mindfulness meditation can be more powerful than morphine. Morphine has been shown to, on average, reduce chronic pain by about 25%. Mindfulness meditation has been shown to, on average, reduce chronic pain by about 40% and in some cases up to 93% with short-term and long-term benefits. It’s simply the act of bringing your awareness to what you’re actually experiencing in the present moment without judgment. We found that with mindfulness, patients with chronic pain and depression and anxiety are more able to differentiate between the physical sensations in the body and the thoughts about the sensations—the memories around pain or resentment around pain or anxiety. With people who cope with chronic pain by either feeling overwhelmed and anxious or who feel like they want to check out from their experience, who want to ignore or get away from their pain, we found that mindfulness is a great bridge to bring them back to the present moment, with nonjudgment. To think “What are the actual sensations that I’m experiencing right now?” or “What does this pain feel like?” and “Can I bring courage to be with it rather than to fight it or ignore it?” Over time, the more chronic pain patients do this, the more gray matter is actually grown in the prefrontal cortex, the stronger the thalamus is, and the insula, in helping to know which pain signals are worth paying attention to and to increase proprioception inside the body and also deactivate portions of the amygdala that decreases the emotional response to pain, which is often very harmful and actually increases pain.

Treating Postoperative Acute Pain: New Frontiers Charles Argoff md, cpe

Surveys show 95% of the drugs that are used to control acute postoperative pain are opioid-based and that’s been done for many years. There is a general movement through the anesthesia and surgical community to what’s known as enhanced recovery after surgery, or eras. There are even national organizations that support this. Using multimodal therapy, which is another way of saying opioid sparing approaches, we can enhance recovery, reduce length of hospital stay, and reduce chronic pain. What it comes down to

56 PWJ | www.painweek.org

is, what can we do that’s different? We can address acute pain with assessment and measures to pre-, intra-, and postoperatively manage people’s pain more aggressively. With respect to who is at risk, it’s very important to recognize at-risk factors—habits, lifestyle, smoking, other premorbid conditions—before the person undergoes treatment, so that the most careful care can be given to preventing those morbidities from complicating their recovery. What’s very interesting, coming out of Nobel Prize-winning chemistry work, is a new understanding of mu receptor activation. It turns out, when the mu receptors are activated, that downstream it can activate a pathway, called the beta-arrestin pathway, which is what’s responsible for most of the side effects, as well as pathways which are responsible for the analgesic effects. And it has been understood for years that G protein signaling agents can allow for a more selective downstream activation of the positive aspects of an opioid while minimizing the activity of the downstream pathways that you would not want to activate. In plain language, you get the analgesia without activating the beta-arrestin pathway, which is where novel analgesics in this class are being developed that might take us to a whole new plateau.

Abuse Deterrent Formulations: Part of the Opioid Balancing Act

Jeremy Adler ms, pa-c

The idea of making an opioid safer is very desirable, and the current approach has been to address certain components of the way these drugs are abused. Most of the products we’ve focused on are abused through nasal snorting or through injection. We have technologies that resist crushing. So if somebody seeks this type of medication through illegitimate pathways, the hope is that they won’t be able to powderize it and then snort it or inject it. There are ways that make tablets more difficult to manipulate: gelling agents are added so products will form a substance that’s not easy to snort or inject. We have drugs that have antagonists within them which can be released upon manipulation and, therefore, either reduce the euphoria or the desirability of the products. We have irritant substances that make them less desirable. I think we’re headed in the right direction, and engineers are hard at work trying to come up with new technologies to improve the safety of these medications while keeping them available for those patients who really need them. There are parallels to the auto industry and the number of motor vehicle fatalities when the industry started out. Automakers introduced technologies—brake assist, seatbelts and airbags, crush resistant zones—that had a positive effect. But what’s important is that these technologies did not replace the need to pick people who can operate vehicles safely; they don’t stop vehicles from crashing. In terms of opioids, I think we are moving in that direction as well; the industry is doing what they can to engineer products that are less manipulatable and less desirable. It’s very important though that we as healthcare professionals remember that we still have to pick the right patients to provide these products to, that our patient selection is still is paramount and we have to take into account the whole patient assessment process and risk stratification when we’re utilizing opioids of any sort. So although these technologies exist, they don’t replace our responsibility in patient selection.

Q1 | 2017

Interprofessional Education: Communication, Goals, and Barriers Sondra M. Adkinson pharmd, daapm, cpe, bsph

Interprofessional education (ipe) has primary goals: to improve outcomes; to reach the population in a healthcare setting where teams can actually provide cost-effectiveness to lower our healthcare costs; and to reach unreached areas. We do the latter with teams: in the IPE model, patients are at the center and the team has responsibilities and skills that intercoordinate. Because of their specific skill sets, they can provide that care in some of our more unreached areas, which is one of the reasons why the World Health Organization is behind ipe—to reach more of the unreached and the isolated healthcare areas. That standard would go a long way towards public health, improving patient outcomes, and lowering the cost of care. Barriers come in the form of communication. That’s where the universities and colleges are actually employing the faculty with mentoring and coaching training so they can improve communication skills within each of the professions, whether it’s physicians, nurses, pharmacists, physical therapists, respiratory therapists, social workers. Not letting any one team member be the leader who prevents the other skill sets from contributing. Some of the other barriers are administrative, financial. Some campuses have actual land-lock problems where resources in buildings are the obstacle. Some of the medical libraries are not a shared work center where the teams can meet in small groups as a place where they can get their projects off and into the community.

Biobehavioral Pain Therapies: What’s in the Toolbox? Dawn Buse phd

Biobehavioral treatments are a great addition to the toolkit that primary care providers already have. Not only can they help with managing the pain condition, they can help with all sorts of associated symptoms like depression and anxiety, frustration and lack of self-efficacy, as well as with adherence and motivation. The options for nonpharmacologic migraine management with the strongest evidence include cognitive behavioral therapy, which includes training in stress management, biofeedback, and relaxation. All 3 of these can be taught to patients who live with

Q1 | 2017

migraine to help both prevent attacks and to reduce the duration, severity, and intensity of attacks when they do occur. They can be combined with medication or done independently and are great treatment options especially for women who are considering pregnancy, pregnant, or lactating, since they do not carry side effects that some medications do. They’re also cost effective and good for patients who may want to avoid medication. However, research shows that their best efficacy is when they’re combined with the most appropriate and optimized pharmacologic treatment. In 3 different meta-analyses comparing biofeedback, cognitive behavioral therapy, and relaxation training with a preventive pharmacologic agent, the outcome of using just one or the other was on a similar efficacy range. However, in 3 different studies that combined the pharmacologic and the nonpharmacologic treatment, the outcomes were far superior with more than 70% of people showing good response to the combined treatment. Some of these treatments, particularly dealing with relaxation, can be self-taught or learned by the patient on their own. I have guided visual imagery, diaphragmatic breathing, and progressive muscle relaxation exercises available free on my personal website, which is dawnbuse.com, and there are free apps available through iTunes or Google Play. Biofeedback is something that’s taught and engaged with a psychologist, possibly an occupational therapist or physical therapist. To find a practitioner, there are links on the Association for the Advancement of Physiologic and Biofeedback Therapies (aapb) website. For cognitive behavioral therapy, you’ll want to look for a psychologist with training in the technique, and it’s good if they have a background in either chronic pain or migraine because there are some specific things we do when we’re working with cbt for chronic pain. To find a practitioner, you can look on the society for behavioral medicine website, the Association for the Advancement of Behavioral and Cognitive Therapies (aabct) website, or the American Psychological Association (apa) website. It’s very important when making a referral that the primary clinician clarify they’re not abandoning the patient; that they believe the patient has a biologic/neurologic condition, which they are going to continue to treat, but they’re really just bringing on a team member into the care team. When a patient hears “psychology/psychologist,” it’s really easy for them to think “Oh no, my doctor thinks I’m crazy. My healthcare professional thinks this is all in my head and this isn’t real.” So start by saying “I’m adding a member to our team. You have a real biologic/neurologic condition. We’re just going to add some more tools to our armamentarium to best treat you.”

www.painweek.org | PWJ

SHORT CUTS

with

sanford m.

silverman

58 PWJ | www.painweek.org

Q1 | 2016

“…medical school seemed like a good idea —a noble profession.”

Q What inspired you to become a healthcare provider?

I was always interested in science. I majored in chemical engineering and, after my junior year of college, decided it was not for me. I had interest in the biological side of engineering, and medical school seemed like a good idea—a noble profession.

Why did you focus on pain management?

Anesthesiologists have always been at the forefront of pain management. I remember being the Pain Clinic Director at William Beaumont Army Medical Center in 1990, and we wrote only 3 medications: ibuprofen, Elavil®, and trazodone. The science and practice of pain medicine was rudimentary. It exploded in the 1990s and so did my interest, particularly connecting with patients outside of the operating room.

Who were your mentors?

I had no formal pain management fellowship. I guess I learned most of this on my own, attending conferences and workshops. My interest in pain medicine came after my training in anesthesiology. With respect to addiction

Q1 | 2017

medicine, I have to credit Steve Passik as my mentor. He truly inspired me to look beyond the establishment of pain medicine, and to explore a different paradigm to treat patients with chronic pain and substance use disorders.

Q If you weren’t a healthcare provider, what would you be?

A biomedical engineer. I studied chemical engineering and received a BS/MS, and that’s where I was headed until I did an internship in engineering consulting over the summer, which changed my career path.

What is your most marked characteristic?

INTENSITY. I am serious, sometimes too much. Yet I have a pretty good sense of humor. But my background is problem-solving, so when I see a patient with a problem, I am looking for a solution.

Q What do you consider your greatest achievement?

a Bicycling across the US in the summer of 1979 with a childhood friend. I think about that a lot, and maybe doing it again someday. I recently www.painweek.org | PWJ

PUNDiT PROFiLe/SiLVeRMaN

“I am serious, sometimes too much. Yet I have a pretty good sense of humor. But my background is problem-solving, so when I see a patient with a problem, I am looking for a solution.”

published a text: Controlled Substance Management in Chronic Pain: A Balanced Approach. This was truly a labor of love. It was important to me to consolidate all the great lectures and advise from great people in one text so others could practice safely and effectively.

What is your favorite language?

English.

Q If you had to choose one book, one film, and one piece of music to take into space for an undetermined amount of time, what would they be?

I love the movie Fail Safe, which I consider one of the best movies ever made. My book would be Zen and the Art of Motorcycle Maintenance, which I read on my bicycle trip in 1979. Music would have to be Handel’s Water Music and Music for the Royal Fireworks.

60 PWJ | www.painweek.org

What would you like your legacy to be?

The person who made a difference, helping just a little to positively affect one’s life. Isn’t that the reason we all went into medicine?

What is your motto?

a Always shoot for 100%, never less. That does not mean you do not have to accept less, but ya gotta try for the big banana! And if you don’t get to 100% and you know you tried, that’s just fine! Sanford M. Silverman is ceo and Medical Director of Comprehensive Pain Medicine in Pompano Beach, Florida.

Q1 | 2017

GRALISE® (gabapentin) tablets Rx Only BRIEF SUMMARY OF FULL PRESCRIBING INFORMATION This does not include all the information needed to use GRALISE safely and effectively. See full Prescribing Information for GRALISE. INDICATIONS AND USAGE • GRALISE is indicated for the management of postherpetic neuralgia. • GRALISE is not interchangeable with other gabapentin products because of differing pharmacokinetic profiles that affect the frequency of administration. DOSAGE AND ADMINISTRATION • GRALISE should be titrated to an 1800 mg dose taken orally, once-daily, with the evening meal. GRALISE tablets should be swallowed whole. Do not crush, split, or chew the tablets. For recommended titration schedule, see DOSAGE AND ADMINISTRATION in full Prescribing Information. • If GRALISE dose is reduced, discontinued, or substituted with an alternative medication, this should be done gradually over a minimum of 1 week or longer (at the discretion of the prescriber). • Renal impairment: Dose should be adjusted in patients with reduced renal function. GRALISE should not be used in patients with CrCl less than 30 mL/min or in patients on hemodialysis. CONTRAINDICATIONS GRALISE is contraindicated in patients with demonstrated hypersensitivity to the drug or its ingredients. WARNINGS AND PRECAUTIONS GRALISE is not interchangeable with other gabapentin products because of differing pharmacokinetic profiles that affect the frequency of administration. The safety and effectiveness of GRALISE in patients with epilepsy has not been studied. Suicidal Behavior and Ideation Antiepileptic drugs (AEDs), including gabapentin, the active ingredient in GRALISE, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Table 1: Risk by Indication for Antiepileptic Drugs (including gabapentin, the active ingredient in GRALISE) in the Pooled Analysis

Indication Epilepsy Psychiatric Other Total

Placebo Patients with Events Per 1000 Patients 1.0 5.7 1.0 2.4

Relative Risk: Risk Incidence of Difference: Events in Drug Additional Drug Patients Patients/Incidence Drug Patients with Events Per in Placebo with Events Per 1000 Patients Patients 1000 Patients 3.4 3.5 2.4 8.5 1.5 2.9 1.8 1.9 0.9 4.3 1.8 1.9

The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications. Anyone considering prescribing GRALISE must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which products containing active components that are AEDs (such as gabapentin, the active component in GRALISE) are prescribed, are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated. Patients, their caregivers, and families should be informed that GRALISE contains gabapentin, which is also used to treat epilepsy and that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers. Withdrawal of Gabapentin Gabapentin should be withdrawn gradually. If GRALISE is discontinued, this should be done gradually over a minimum of 1 week or longer (at the discretion of the prescriber). Tumorigenic Potential In standard preclinical in vivo lifetime carcinogenicity studies, an unexpectedly high incidence of pancreatic acinar adenocarcinomas was identified in male, but not female, rats. The clinical significance of this finding is unknown. In clinical trials of gabapentin therapy in epilepsy comprising 2,085 patient-years of exposure in patients over 12 years of age, new tumors were reported in 10 patients, and pre-existing tumors worsened in 11 patients, during or within 2 years after discontinuing the drug. However, no similar patient population untreated with gabapentin was available to provide background tumor incidence and recurrence information for comparison. Therefore, the effect of gabapentin therapy on the incidence of new tumors in humans or on the worsening or recurrence of previously diagnosed tumors is unknown. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as Multiorgan Hypersensitivity, has been reported in patients taking antiepileptic drugs, including GRALISE. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, and/or lymphadenopathy in association with other organ system involvement, such as hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its expression, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, the patient should be evaluated immediately. GRALISE should be discontinued if an alternative etiology for the signs or symptoms cannot be established. Laboratory Tests Clinical trial data do not indicate that routine monitoring of clinical laboratory procedures is necessary for the safe use of GRALISE. The value of monitoring gabapentin blood concentrations has not been established. ADVERSE REACTIONS Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In clinical trials in patients with postherpetic neuralgia, 9.7% of the 359 patients treated with GRALISE and 6.9% of 364 patients treated with placebo discontinued prematurely due to adverse reactions. In the GRALISE treatment group, the most common reason for discontinuation due to adverse reactions was dizziness.

Table 2: Treatment-Emergent Adverse Reaction Incidence in Controlled Trials in Neuropathic Pain Associated with Postherpetic Neuralgia (Events in at Least 1% of all GRALISE-Treated Patients and More Frequent Than in the Placebo Group) Body System – Preferred Term Ear and Labyrinth Disorders Vertigo Gastrointestinal Disorders Diarrhea Dry mouth Constipation Dyspepsia General Disorders Peripheral edema Pain Infections and Infestations Nasopharyngitis Urinary tract infection Investigations Weight increased Musculoskeletal and Connective Tissue Disorders Pain in extremity Back pain Nervous System Disorders Dizziness Somnolence Headache Lethargy

GRALISE N = 359 %

Placebo N = 364 %

1.4

0.5

3.3 2.8 1.4 1.4

2.7 1.4 0.3 0.8

3.9 1.1

0.3 0.5

2.5 1.7

2.2 0.5

1.9

0.5

1.9 1.7

0.5 1.1

10.9 4.5 4.2 1.1

2.2 2.7 4.1 0.3

The following adverse reactions with an uncertain relationship to GRALISE were reported during the clinical development for the treatment of postherpetic neuralgia. Events in more than 1% of patients but equally or more frequently in the GRALISE-treated patients than in the placebo group included blood pressure increase, confusional state, gastroenteritis, viral herpes zoster, hypertension, joint swelling, memory impairment, nausea, pneumonia, pyrexia, rash, seasonal allergy, and upper respiratory infection. Postmarketing and Other Experience with Other Formulations of Gabapentin In addition to the adverse experiences reported during clinical testing of gabapentin, the following adverse experiences have been reported in patients receiving other formulations of marketed gabapentin. These adverse experiences have not been listed above and data are insufficient to support an estimate of their incidence or to establish causation. The listing is alphabetized: angioedema, blood glucose fluctuation, breast enlargement, elevated creatine kinase, elevated liver function tests, erythema multiforme, fever, hyponatremia, jaundice, movement disorder, Stevens-Johnson syndrome. Adverse events following the abrupt discontinuation of gabapentin immediate release have also been reported. The most frequently reported events were anxiety, insomnia, nausea, pain, and sweating. DRUG INTERACTIONS In vitro studies were conducted to investigate the potential of gabapentin to inhibit the major cytochrome P450 enzymes (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4) that mediate drug and xenobiotic metabolism using isoform selective marker substrates and human liver microsomal preparations. Only at the highest concentration tested (171 mcg/mL; 1mM) was a slight degree of inhibition (14% to 30%) of isoform CYP2A6 observed. No inhibition of any of the other isoforms tested was observed at gabapentin concentrations up to 171 mcg/mL (approximately 15 times the Cmax at 3600 mg/day). Hydrocodone Coadministration of gabapentin immediate release (125 mg and 500 mg) and hydrocodone (10 mg) reduced hydrocodone Cmax by 3% and 21%, respectively, and AUC by 4% and 22%, respectively. The mechanism of this interaction is unknown. Gabapentin AUC values were increased by 14%; the magnitude of the interaction at other doses is not known. Antacid (containing aluminum hydroxide and magnesium hydroxide) An antacid containing aluminum hydroxide and magnesium hydroxide reduced the bioavailability of gabapentin immediate release by approximately 20%, but by only 5% when gabapentin immediate release was taken 2 hours after the antacid. It is recommended that GRALISE be taken at least 2 hours following the antacid (containing aluminum hydroxide and magnesium hydroxide) administration. Drug/Laboratory Test Interactions False positive readings were reported with the Ames-N-Multistix SG® dipstick test for urine protein when gabapentin was added to other antiepileptic drugs; therefore, the more specific sulfosalicylic acid precipitation procedure is recommended to determine the presence of urine protein. USE IN SPECIFIC POPULATIONS Pregnancy Category C: GRALISE should be used during pregnancy or in women who are nursing only if the benefits clearly outweigh the risks. See full Prescribing Information for more information about use of GRALISE in pregnancy. Pediatric Use The safety and effectiveness of GRALISE in the management of postherpetic neuralgia in patients less than 18 years of age has not been studied. Geriatric Use The total number of patients treated with GRALISE in controlled clinical trials in patients with postherpetic neuralgia was 359, of which 63% were 65 years of age or older. The types and incidence of adverse events were similar across age groups except for peripheral edema, which tended to increase in incidence with age. Renal Impairment GRALISE is known to be substantially excreted by the kidney. Dosage adjustment is necessary in patients with impaired renal function. GRALISE should not be administered in patients with CrCl between 15 and 30 or in patients undergoing hemodialysis. [see Dosage and Administration in full Prescribing Information]. DRUG ABUSE AND DEPENDENCE The abuse and dependence potential of GRALISE has not been evaluated in human studies. OVERDOSAGE Acute oral overdoses of gabapentin immediate release in humans up to 49 grams have been reported. In these cases, double vision, slurred speech, drowsiness, lethargy and diarrhea were observed. All patients recovered with supportive care. Gabapentin can be removed by hemodialysis. Although hemodialysis has not been performed in the few overdose cases reported, it may be indicated by the patient’s clinical state or in patients with significant renal impairment.

ONCE daily with EVENING MEAL

Bring 24-hour relief into their routine GRALISE is the only once-a-day gabapentinoid that offers Night to Day control of PHN pain1

ONCE daily with

EVENING MEAL

ONCE daily with

EVENING • Patients receiving GRALISE experienced significant pain reduction vs placebo beginning Week 1 and continuing MEAL throughout the 10-week study (P<0.05)2,3

•Average daily pain score reduction for GRALISE was -2.1 vs -1.6 with placebo (P=0.013)2 Study Design: Patients from 89 investigative sites participated in this randomized, double-blind, parallel design, placebo-controlled, multicenter clinical trial. The study period included a 1-week baseline period, followed by randomization and a 2-week titration to a once-daily dose of 1800 mg G-GR or matched placebo, followed by an 8-week maintenance-dose period, followed by a 1-week dose-tapering period. 452 patients were randomized, with 221 receiving 1800 mg of GRALISE and 231 receiving placebo.2 Primary endpoint: change in the baseline observation carried forward (BOCF) average daily pain score from the baseline week to Week 10 of the efficacy treatment period.2

Learn more today at www.Gralise.com INDICATIONS AND USAGE GRALISE is indicated for the management of postherpetic neuralgia (PHN). GRALISE is not interchangeable with other gabapentin products because of differing pharmacokinetic profiles that affect the frequency of administration. IMPORTANT SAFETY INFORMATION ADVERSE REACTIONS The most common side effects were dizziness (10.9%) and somnolence (4.5%). USE IN SPECIFIC POPULATIONS Reductions in GRALISE dose should be made in patients with age-related compromised renal function. WARNINGS AND PRECAUTIONS Suicidal Behavior and Ideation Antiepileptic drugs (AEDs) including gabapentin, the active ingredient in GRALISE, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.

For more information about GRALISE, please see Brief Summary on the following page. References: 1. GRALISE [prescribing information]. Newark, CA: Depomed Inc.; December 2012. 2. Sang CN, Sathyanarayana R, Sweeney M. Gastroretentive gabapentin (G-GR) formulation reduces intensity of pain associated with postherpetic neuralgia (PHN). Clin J Pain. 2013;29:281-288. 3. Argoff CE, Chen C, Cowles VE. Clinical development of a once-daily gastroretentive formulation of gabapentin for treatment of postherpetic neuralgia: an overview. Expert Opin Drug Deliv. 2012;9:1147-1160.

Relief Uninterrupted