The Rational Use of Opioid Analgesics for Non-Cancer Pain: What Every Prescriber Needs to Know

The Rational Use of Opioid Analgesics for Non-Cancer Chronic Pain: What Every Prescriber Needs to Know

Disclosure Charles Argoff • Consultant/Independent Contractor: Boehringer Ingleheim, Gruenthal Pharmaceuticals, Depomed, Jazz Pharmaceuticals, plc, Insys Pharmaceuticals, Shinogi Pharmaceuticals • Grant/Research Support: Endo Pharmaceuticals, Forest Laboratories, Lilly USA LLC, Neurogesx, Pfizer Inc. • Honoraria: Boehringer Ingleheim,, Depomed Endo Pharmaceuticals, Forest Laboratories, Janssen, Jazz, King, Lilly USA LLC, Neurogesx, Nuvo Research, Pfizer Inc. SanofiAventis, US, LLC • Speakers Bureau: Endo Pharmaceuticals, Forest Laboratories, Janssen Pharmaceuticals, Inc. Lilly USA LLC, Pfizer Inc., Neurogesx

Disclosure • Beth Darnall – Nothing to Disclose

Learning Objectives • Review the evidence supporting the use of chronic opioid therapy in chronic non-cancer pain • Describe the role of opioids as a component of multimodal therapeutic strategies for chronic pain management • Explain the risks and consequences of long term opioid therapy for pain management • Explain the dynamic process of managing a patient with chronic pain especially when being treated with chronic opioid therapy

Chronic Pain • 116 million Americans • Up to $635 billion

IOM (Institute of Medicine). 2011. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. Washington, DC: The National Academies Press.

IMS Institute for Healthcare Informatics

Opioids • Prescription rate is rising • Vicodin: #1 prescribed drug (2006-2010) • Sales of Oxycontin increased almost 4-fold between 2006-2010

Opioids • Greater scrutiny and regulation • Hotly debated • Most can agree we need: - to learn more - to appreciate the knowns and unknowns and improve patient care

The Rational Use of Opioid Analgesics for Non-Cancer Chronic Pain: What Every Prescriber Needs to Know

Charles E. Argoff, M.D.

Rational Use of Opioid Analgesics for Chronic Non- Cancer Pain • Dichotomy of “pro-opioid” and “anti-opioid” is false, and does not serve healthcare professionals, patients, or society well – Ethical healthcare providers are “pro-health” and make treatment decisions within that context

• Clinicians must – Learn how to select patients for opioid therapy, when indicated – Manage patients on opioid therapy as safely and effectively as possible

Establishing Realistic Treatment Outcome Expectations • Non-opioid analgesics • Invasive pain management • Opioid analgesics

“Discouraging Data on the Antidepressant”

Gabapentin in the Treatment of Painful Diabetic Neuropathy* Mean pain score

10

Placebo Gabapentin

8

N=165

6 4

†

†

‡

†

‡

‡

‡

4

5

6

7

8

2 0 Screening

1

2

3

*Not approved by FDA for this use.

Week † P<0.01. ‡ P<0.05.

Adapted from Backonja M et al. JAMA. 1998;280:1831-1836.

Interventional Therapies for Chronic Pain • • • • • • • •

Trigger point injections/Botulinum toxin Epidural Steroid Injection Sacroiliac Joint Injection and RFA Facet Joint Injection and RFA Discography IDET, Nucleoplasty, Disc RFA Spinal Cord Stimulation Spinal Drug Delivery

How good is the Evidence?

APS/AAPM Clinical Guidelines for the Use of Chronic Opioid Therapy in Chronic Noncancer Pain (2009) • • • • • • • • • • • • • •

Patient Selection and Risk Stratification Informed Consent and Opioid Management Plans Initiation and Titration of COT Methadone Monitoring High-Risk Patients Dose Escalations, High-Dose Opioid Therapy, Opioid Rotation, Indications for Discontinuations of Therapy Opioid-Related Adverse Effects Use of Psychotherapeutic Cointerventions Driving and Work Safety Identifying a Medical Home and When to Obtain Consultation Breakthrough Pain Opioids in Pregnancy Opioid Policies

Chou R et al. J Pain. 2009;10(2):113-130 APS: American Pain Society/AAPM: American Academy of Pain Medicine

Pharmacotherapy Opioids, nonopioids, adjuvant analgesics

Interventional Approaches

Physical Medicine and Rehabilitation Assistive devices, electrotherapy

Complementary and Alternative Medicine

Multimodal Therapeutic Strategies for Pain and Associated Disability

Injections, neurostimulation

Psychological Support Psychotherapy, group support

Massage, supplements

Lifestyle Change Exercise, weight loss

Fine PG, et al. J Support Oncol. 2004;2(suppl 4):5-22; Portenoy RK, et al. In: Lowinson JH, et al, eds. Substance Abuse: 17 A Comprehensive Textbook. 4th ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 2005:863-903.

Opioids

Effective for Many Types of Pain Postoperative

Cancer

Osteoarthritis

Neuropathic

Low back

Caldwell JR, et al. J Pain Symptom Manage. 2002;23(4):278-291; Despande A, et al. Cochrane Database Syst Rev. 2007:CD004959; Eisenberg E, et al. JAMA. 2005;293(24):3042-3052; Fitzgibbon DR. Curr Pain Headache Rep. 2007;11(4):251-258; Hudcova J, et al. Cochrane Database Syst Rev. 2006:CD003348.

18

Need to Balance Access to Pain Medications with Abuse Prevention

Increased rate of misuse, abuse, and diversion1

Reduced access to opioids for legitimate pain problems1

1 Kuehn BM. JAMA. 2007;297:249-250. [Kuehn 2007, p249-250

Accurate pain assessment Risk stratification Develop a treatment plan

WHAT CAN WE CLINICIANS DO?

Proposed Critical Thinking Model for Chronic Opioid Therapy Patient Selection

Initial Patient Assessment

Comprehensive Pain Management Plan

Trial of Opioid Therapy

Patient Reassessment

Continue Opioid Therapy

31

Implement Exit Strategy

Alternatives to Opioid Therapy

Goals of Clinical Assessment • Achieve diagnosis of pain • Identify and treat underlying causes of pain if possible • Identify and treat comorbid conditions • Evaluate psychosocial factors • Evaluate functional status (activity levels) • Set goals • Develop a targeted treatment plan • Determine whether a consultation is needed

Evaluation of the Patient • Medical history • Physical exam • Review of prior work up, diagnostic tests, prior treatment • Document the nature, intensity, location of pain, effect of pain on physical and psychological function • History of substance abuse

Pain Assessment Scales Visual Analog Scale1

Verbal Pain Intensity Scale1 No pain

Mild Moderate Severe Very Worst pain pain pain severe possible pain pain

0–10 Numeric Pain Intensity

0 No pain

1

2

3

4

5

6

Moderate pain

7

8

“Faces” Scale3

Scale2

9

10

Worst possible pain

Worst possible pain

No pain

0

1

2

3

4

5

1. Portenoy RK, Kanner RM, eds. Pain Management: Theory and Practice. 1996:8-10.

2. McCaffery M, Pasero C. Pain: Clinical Manual. Mosby, Inc. 1999:16.

3. Wong DL. Waley and Wong’s Essentials of Pediatric Nursing 5th ed. 1997:1215-1216.

Patient Selection • Persistent pain despite reasonable trials of nonopioid analgesics and adjuvants or • Moderate to severe pain (≥4-5 on a 10-point scale) requiring rapid relief or • Patient characteristics contraindicate use of other analgesics and • Benefits of opioid therapy are likely to outweigh risks based upon comprehensive assessment See 2009 APS/AAPM Guideline Sections 1.1-1.3 34

Risk Assessment Principles of Responsible Prescribing

RISK STRATIFICATION

10 Principles of Universal Precautions 1.

2.

3.

4.

5.

6.

7.

8.

Diagnosis with appropriate differential Psychological assessment including risk of addictive disorders Informed consent (verbal or written/signed) Treatment agreement (verbal or written/signed) Pre-/post-intervention assessment of pain level and function Appropriate trial of opioid therapy adjunctive medication Reassessment of pain score and level of function Regularly assess the “Four A’s” of pain medicine: Analgesia, Activity, Adverse Reactions, and Aberrant Behavior 9. Periodically review pain and comorbidity diagnoses, including addictive disorders 10. Documentation Gourlay DL, Heit HA. Pain Med. 2009;10 Suppl 2:S115-123.

Gourlay DL, et al. Pain Med. 2005;6(2):107-112.

Risk Factors for Aberrant Behaviors/Harm Biological

• Age ≤ 45 years • Gender • Family history of prescription drug or alcohol abuse

• Cigarette smoking

Psychiatric

Social

• Substance use disorder

• Preadolescent sexual abuse (in women)

• Major psychiatric disorder (eg, personality disorder, anxiety or depressive disorder, bipolar disorder)

• Prior legal problems

• History of motor vehicle accidents

• Poor family support

• Involvement in a problematic subculture

Katz NP, et al. Clin J Pain. 2007;23:103-118; Manchikanti L, et al. J Opioid Manag.

2007;3:89-100.

Webster LR, Webster RM. Pain Med. 2005;6:432-442.

Opioid Risk

Assessment and Guidance • Questionnaires – – – –

Current Opioid Misuse Measure (COMM) Diagnosis, Intractability, Risk, and Efficacy (DIRE) Opioid Risk Tool (ORT) Screener and Opioid Assessment for Patients in Pain–Revised (SOAPP-R) – Screening Instrument for Substance Abuse Potential (SISAP)

• Opioid treatment agreement • Urine drug testing (UDT) Butler SF, et al. J Pain. 2008;9(4):360-372; Katz NP, et al. Clin J Pain. 2007;23(2):103-118; 29 Manchikanti L, et al. J Opioid Manag. 2007;3(2):89-100; Webster LR, Webster RM. Pain Med. 2005;6(6):432-442.

ORT Mark each box that applies Female 1. Family history of substance abuse Alcohol 1 Illegal drugs 2 Prescription drugs 4 2. Personal history of substance abuse Alcohol 3 Illegal drugs 4 Prescription drugs 5 3. Age (mark box if between 16 and 45 years)  1 4. History of preadolescent sexual abuse 3 5. Psychological disease 2 ADD, OCD, bipolar, schizophrenia Depression 1 Scoring totals ____

ADD, attention-deficit disorder; OCD, obsessive-compulsive disorder.

Webster LR, Webster RM. Pain Med. 2005;6(6):432-442.

Male 3 3 4 3 4 5 1 0 2 1 ____

Administration  Initial visit  Prior to opioid therapy

Scoring  0-3 (6%): low risk  4-7 (28%): moderate risk  ≥8 (91%): high risk Percentages indicate proportion of classified patients who exhibited an aberrant behavior

30

Screener and Opioid Assessment for Patients with Pain (SOAPP®) Short Form To score the SOAPP-SF, add ratings of all questions.

A score of 4 or higher on this 5-question version of the SOAPP-SF is considered high risk.

Score = 3

Multiple versions of the SOAPP are available at PainEDU.org

© 2012 Inflexxion, Inc. Permission granted solely for use in published format by individual practitioners in clinical practice.

No other uses or alterations are authorized or permitted by copyright holder. Permissions questions: PainEDU@inflexxion.com.

The SOAPP® was developed with grants from the National Institutes of Health and an educational grant from Endo Pharmaceuticals.

27

STRATIFY RISK LOW RISK • No past/current history of substance abuse • Noncontributor y family history of substance abuse • No major or untreated psychological disorder

MODERATE RISK • History of treated substance abuse • Significant family history of substance abuse • Past/comorbid psychological disorder

Webster LR, Webster RM. Pain Med. 2005;6:432-442.

HIGH RISK • Active substance abuse • Active addiction • Major untreated psychological disorder • Significant risk to self and practitioner

Principles for Responsible Prescribing • I have resolved key points before initiating opioid therapy – Diagnosis established and opioid treatment plan developed – Established level of risk – I can treat this patient alone/I need to enlist other consultants to comanage this patient (pain or addiction specialists)

• I have considered nonopioid modalities – Pain rehabilitation program – Behavioral strategies – Non-invasive and interventional techniques

Based on Presentation and Type of Pain TREATMENT OPTIONS

Approach to Treatment of Pain Diagnosis Treat underlying condition/symptomatic treatment

Reduce pain

Prevention (if applicable) Improve physical functioning

Reduce psychological distress

Improve overall quality of life

Adapted from Turk DC. Clin J Pain. 2000;16:279-280.

Osteoarthritis Treatment Options Considered Before Opioids • Exercise – Aquatic/aerobic strengthening

• • • • •

Self-management Education Braces Patellar tape TENS/acupuncture

• • • • • • • •

NSAIDs + PPI NSAIDs + misoprostol COX-2 inhibitors Glucosamine Chondroitin Topical NSAIDs Topical capsaicin IA corticosteroids

COX-2, cyclooxygenase-2; IA, intra-articular; PPI, proton-pump inhibitor; NSAID, nonsteroidal anti-inflammatory drugs; TENS, transcutaneous electrical nerve stimulation.

36 Zhang W, et al. Osteoarthritis Cartilage. 2007;15(9):981-1000.

Low Back Pain Treatment Options Considered Before Opioids • • • • •

Exercise TENS/acupuncture Osteopathy Facet joint injections Epidural/SNR injections

• • • • •

Acetaminophen ???

NSAIDs -???

Antidepressants- ???

Gabapentin- ???

Topiramate -???

37

Neuropathic Pain Treatment Options Considered Before Opioids • Nondrug therapy – – – –

Education TENS Spinal cord simulation Entrapment release

• Pharmacotherapy – – – – – – –

TCAs SNRIs Pregabalin/gabapentin Other anticonvulsants Topical lidocaine Topical capsaicin NMDA antagonists

NMDA, N-methyl-D-aspartate; SNRI, serotonin norepinephrine reuptake inhibitor; TCA, tricyclic antidepressent.

Attal N, et al. Eur J Neurol. 2006;13(11):1153-1169; Cruccu G, et al. Eur J Neurol. 2007;14(9):952-970; Dworkin RH, et al. Pain. 2007;132(3):237-251.

38

Opioids on the NNT Map of Pharmacotherapy of NP

•

TCAs

397

• 83

Valproate

• 109

LTG/CBZ/PHT

• 149 • 150

Opioids Tramadol Gabapentin/pregabalin

1057

•

Mexiletine SNRIs NMDA antagonists

120

•• • 193

466

Capsaicin SSRIs

309

•

Topiramate

0

2

4

• 214 8

6

NNT CBZ, carbamazepine; LTG, lamotrigene; NNT, numbers needed to treat; PHT, phenytoin; SSRI, selective serotonin reuptake inhibitor.

Finnerup NB, et al. Pain. 2005;118(3):289-305.

81

39

10

12

Neuropathic Pain

Recommendations of Various Societies EFNS, Europe Neurology First line

TCA GBP/PGB Lidocaine 5% plaster

Canadian Pain Society

IASP NeuPSIG

TCA GBP/PGB

TCA, SNRI GBP/PGB Lidocaine 5% Opioid (specific circumstances)

Second line

Third line

Fourth line

SNRI (Opioid) Opioid Lamotrigine Capsaicin

SNRI Lidocaine 5% Opioid (except methadone)

Methadone

EFNS, European Federation of Neurological Societies; IASP, International Association for the Study of Pain; NeuPSIG, Neuropathic Pain Special Interest Group.

Attal N, et al. Eur J Neurol. 2006;13(11):1153-1169; Dworkin RH, et al. Pain. 2007;132(3):237-251; 40 Moulin DE, et al. Pain Res Manag. 2007;12(1):13-21.

Opioid Tramadol Paroxetine Bupropion NMDA antagonist

Equivocal Response to Opioids • Headache (except rare TAC) – Uncertain effect – Rebound analgesic headache

• Chronic abdominal nonspecific pain – No evidence base

• Chronic pelvic pain – No evidence base

• Central pain and fibromyalgia – Opioid receptor dysfunction TAC, trigeminal autonomic cephalalgia.

41

Opioid Selection • No one best opioid, or “drug of choice” • Large individual variation in the response to different opioids • Decision to use one drug over another based on – Clinician experience – Prior patient experience – Formulation availability – Cost and third-party coverage Portenoy RK, Payne R, Passik S: Acute and chronic pain. In Lowinson JH, Ruiz P, Millman RB, eds. Comprehensive Textbook of Substance Abuse. Fourth Edition. Baltimore: Williams and Wilkins; 2005:863-903.

Opioid Therapy: Benefits/Risks BEFORE starting a trial of opioid therapy, benefits/risks, alternatives to opioid therapy, and patient concerns should be discussed Benefits

Reduction in pain Reduction in pain-related impairment Improved function and quality of life

Risks

Sedation/confusion

Tolerance

Nausea/dizziness

Physical dependence

Constipation

Pruritus

Gonadal suppression

Addiction

Respiratory suppression

Withdrawal

Sleep apnea

Increased pain Death (rarely)

33

Ongoing Assessment The 4 Aâ&#x20AC;&#x2122;s

Adverse Events

Analgesia Pain relief

Side effects

Activities of Daily Living

Aberrant Drug-Taking

Psychosocial functioning QoL

Misuse Abuse Diversion

Passik SD, Kirsh KL. J Support Oncol. 2005;3(1):83-86.

Passik SD, et al. Clin Ther. 2004;26(4):552-561.

44

Definitions Associated With Opioid Use Addiction

Pseudoaddiction

Primary, chronic, neurobiologic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations.

May be characterized by impaired control over drug use, compulsive use, continued use despite harm, and craving Syndrome resulting from undertreatment of pain that is misidentified by the clinician as inappropriate drug-seeking behavior. Behavior ceases when adequate pain relief is provided. Not a diagnosis; rather, a description of a clinical interaction

Physical dependence

State of adaptation manifested by a drug class specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and administration of an antagonist

Tolerance

State of adaptation in which exposure to a given drug dose induces biologic change resulting in diminution of one or more of the drugâ&#x20AC;&#x2122;s effects over time. Alternatively, escalating doses of a drug are required over time to maintain a given level of effect .

58

When You Suspect Patients Are Abusing Their Medication DO

DON’T

• Perform a thorough exam • Make sure chart includes

• Take their word for it • Dispense drugs without evaluating potential of drug-seeking behavior • Work outside the scope of professional practice • Work without a formal practitioner–patient relationship

– – – –

Photocopy of identification Social security number Telephone number Address

• Confirm patient’s history – Previous practitioner – Pharmacy – Hospital

• Limit quantities prescribed

Drug Enforcement Agency. http://www.deadiversion.usdoj.gov/pubs/brochures/drugabuser.htm. 46 Accessed May 19, 2008.

Aberrant Drug-Taking Behaviors Major

Minor

• • •

•

• • • • •

Selling prescription drugs Prescription forgery Stealing or borrowing another patient’s drugs Injecting or snorting oral formulation Obtaining prescription drugs from nonmedical sources Concurrent abuse of related illicit drugs Multiple unsanctioned dose escalations Recurrent prescription losses

• • • • • •

Aggressive complaining about need for higher doses Drug hoarding during periods of reduced symptoms Requesting specific drugs Acquisition of similar drugs from other medical sources Unsanctioned dose escalation 1-2 times Unapproved use of the drug to treat another symptom Reporting psychic effects not intended by the clinician

Passik SD et al. Oncology (Williston Park). 1998;12(4):517-521,524; 1998;12(5):729-734,736.

61

Aberrant Behaviors With Chronic Pain Patientsa Patients Exhibiting Behaviors, %

60

55.4

50 40 30

25.3

20

8.5

10

6.7

0 0

1-2

3-4

5-7

Number of Aberrant Behaviors per Patient N=388 patients with chronic noncancer pain treated with opioids.

Passik SD. Clin Ther. 2004;26(4):552-561.

Passik SD, et al. J Opioid Manag. 2005;1(5):257-266. a

48

4.1 â&#x2030;Ľ8

Urine Drug Testing (UDT) • Two methods of testing typically used1 – Immunoassay (screening test)  Lab based or conducted at point of care  Tests only for drug classes; can not pinpoint specific opioids  Less sensitive to semisynthetic and synthetic opioidsa; negative response does not exclude use of these agents – Gas Chromatography-Mass Spectrometry (GC-MS; confirmation test)  Lab based, using either GC-MS or another form of liquid chromatography and MS  Use to supplement immunoassay test, as MS can identify drugs that immunoassays may miss • Chain of possession of urine sample – Must be reliable, consistent, free from risk of tampering by person providing sample, office staff, persons transporting sample, and lab personnel aOxycodone,

54

Consult with lab regarding: • Routine procedures and what drugs screened for routinely • Assay sensitivities • Drug(s) that you want to screen for • Confirmation of reporting unexpected results • Confirmation of checking for adulterated urine (specific gravity, creatinine)

oxymorphone, buprenorphine, fentanyl, methadone

1. Pergolizzi Jet al. Pain Pract. 2010;10(6):497-507.

Opioid Metabolism and Drug-Drug Interactions • Many opioidsa react with cytochrome P450 (CYP 450) isoenzymes, primarily CYP 2D6 and CYP 3A41 – Many nonopioid medications metabolized by same CYP 450 enzyme may alter plasma levels of opioids – Result → increase or decrease opioid effectiveness

• Many drugs also have other pharmacologic and pharmacodynamic interactions with opioids – Pharmacokinetics = what the body does to the drug (absorption, distribution, metabolism, excretion) – Pharmacodynamics = what the drug does to the body/mind (the effects)

aIncluding

codeine, hydrocodone, oxycodone, tramadol, and others.

1. Knotkova H et al. J Pain Symptom Manage. 2009;38(3):426-439.

59

PMPs by State VT

ME

WA MT

ND

OR

MI

WY IA

NE UT

IL

IN

PA OH VA

WV

CO

KS

CA

AZ

NY

WI

SD

ID

NV

NH MA

MN

OK

NM

AK

MD

KY

MO

NC TN SC

AR MS

TX

RI CT NJ DE

AL

GA

States with operational PMPs

LA FL

States with enacted PMP legislation, but program not yet operational States with pending legislation

HI

More information: The National Alliance for Model State Drug Laws (NAMSDL) http://www.namsdl.org The Alliance of States with Prescription Monitoring Programs http://www.pmpalliance.org/ Map Š 2012 The National Alliance for Model State Drug Laws (NAMSDL). Current as of January 11, 2012.

15

When to Consider an Opioid Exit Strategy •

No convincing benefit from opioid therapy despite – Dose adjustment – Side-effect management – Opioid rotation

• •

Poor tolerance at analgesic dose Persistent compliance problems despite – Treatment agreement – Limits

•

Presence of a comorbid condition that makes opioid therapy more likely to harm than help

52 Katz N. Patient Level Opioid Risk Management: A Supplement to the PainEDU.org Manual. Newton, MA: Inflexxion, Inc.; 2007.

Opioid Exit Strategy Possible Paths

• Patient’s behavior consistent with drug addiction

• Patient unable or unwilling to cooperate with outpatient taper

• No apparent addiction problem • Patient able to cooperate with office-based taper

• Refer for addiction management or comanagement

• Provide sufficient opioid for 1-month taper or maintain until admission • Refer to inpatient or outpatient program or similar service as available

• Taper gradually over 1 month • Implement nonopioid pain management (psychosocial support, CBT, PT, nonopioid analgesics)

PT, physical therapy.

53 Katz N. Patient Level Opioid Risk Management: A Supplement to the PainEDU.org Manual. Newton, MA: Inflexxion, Inc.; 2007.

Opioid Therapy

New and Emerging Treatments

• Abuse-resistant – Physical barriers – If barriers defeated, drug becomes available

• Abuse-deterrent – Pharmacologic barriers – If altered, antagonist or irritant released

Webster LR. http://www.emergingsolutionsinpain.com/index.php?option=com_content&task=view&id=301&Itemid=219.

54 Accessed May 27, 2008.

Pragmatics Before Prescribing • •

Assess patient suitability Local arrangements for secure prescribing – Contract (tripartite; bipartite) – Involve only 1 pharmacy – PCP role vs Pain Specialist – System in place to tackle complications, noncompliance, withdrawal

•

Other reasonable treatment options have been considered

PCP, primary care physician.

55

Sorting Out the Types of Risk Risk of Adverse Medical Effects

Risk of Abuse Behaviors

•

• • • • • • • • •

• • • • • • • • •

Chronic obstructive pulmonary disease Dementia Benign prostatic hyperplasia Unstable gait Hazardous environment Pretreatment constipation Hepatic insufficiency Low blood pressure Sleep apnea Accidental overdose and death

History of drug or alcohol abuse Psychiatric history Criminal history Unclear cause of pain History of multiple pain clinicians Unstable home environment Too ingratiating; too demanding “Gut feeling” Accidental or intentional overdose and death

See 2009 APS/AAPM Guideline Sections 1.1-1.3, 6.1-6.2 60

During Treatment…

• Keep accurate records • Assess compliance with treatment (may include urine screening); watch for aberrant drug-seeking behavior • Acknowledge and deal with adverse effects • Have a plan B that includes withdrawal and alternative management approaches • Be prepared to re-examine diagnosis • Understand conversion tables, methods of rotation, specific medical situations (eg, kidney and liver failure) 57

Does dose matter?

• Maintenance dose of morphine ≤120 mg/d – – – –

Oxycodone ≤80 mg/d Methadone ≤40 mg/d Hydromorphone ≤30 mg/d Transdermal fentanyl ≤50 μg/h

• A low-dose trial with a strong opioid suggests whether or not pain is opioid-responsive

Dworkin RH, et al. Pain. 2007;132(3):237-251.

58

Key Principles for Successful Opioid Prescription—Summary • • • • • • •

Diagnosis Natural history of disease (likely progression or not) Drug interactions Opioid hyperalgesia - ?

Management of adverse effects Opioid rotation Awareness about diversion, aberrant drug related behaviours

59

SUMMARY • Appropriate pain prescribing is an urgent need • Multimodal therapies for addressing pain are available • Accurate assessment is important for diagnosis and risk stratification • Resources are available to assist clinicians

Long term opioid use

â&#x20AC;˘ Marketing of opioids for chronic pain began without rigorous study regarding - long term efficacy - risks and consequences

Risks and Consequences of Opioids (1) lack of systematic reviews (2) scattered literature (3) focus on abuse and diversion

Darnall BD, Stacey, BR. Sex differences examined in long-term opioid use: Cautionary notes for prescribing in women. Archives of Internal Medicine. 2012;172(5): 431-432.

Comprehensive Review: Darnall BD, Stacey BR, Chou R. Medical and psychological risks and consequences of long-term opioid therapy in women. Pain Medicine, Sept 2012.

The Knowns • Long term opioid use has increased substantially in the US in the past decade.1 • Women outpacing men2,3 • Opioid prescribing practices in most European settings are conservative compared to the US4,5 _________________________________ 1. Korff MV, Saunders K, Thomas Ray G, et al. De facto long-term opioid therapy for noncancer pain. Clin J Pain. JulAug 2008;24(6):521-527.

2. Compton WM, Volkow ND. Abuse of prescription drugs and the risk of addiction. Drug Alcohol Depend. Jun 2006;83 Suppl 1:S4-7.

3. Parsells Kelly J, Cook SF, Kaufman DW, Anderson T, Rosenberg L, Mitchell AA. Prevalence and characteristics of opioid use in the US adult population. Pain. Sep 15 2008;138(3):507-513.

4. Sullivan MD, Edlund MJ, Fan MY, Devries A, Brennan Braden J, Martin BC. Trends in use of opioids for noncancer pain conditions 2000-2005 in commercial and Medicaid insurance plans: the TROUP study. Pain. Aug 31 2008;138(2):440-449.

5. Lindenhovius AL, Helmerhorst GT, Schnellen AC, Vrahas M, Ring D, Kloen P. Differences in prescription of narcotic pain medication after operative treatment of hip and ankle fractures in the United States and The Netherlands. J Trauma. Jul 2009;67(1):160-164.

Risks & Consequences Misprescription Prescribing for conditions that have little or no efficacy data.

- IBD6 - Fibromyalgia7-8 - Headache9-10 - Many musculoskeletal pain conditions11-13

Reduced Receipt of Preventive Care14 Buckley DI, Calvert JF, Lapidus JA, Morris CD. Chronic opioid therapy and preventive services in rural primary care: an Oregon rural practicebased research network study. Ann Fam Med. May-Jun 2010;8(3):237-244.

Endocrine Dysregulation • Reduced growth hormone • Reduced fertility in reproductive age women15 • Reduced levels of sex steroids for both pre-and post-menopausal women15 • Younger women may bet at greater risk16

Neonatal Risks â&#x20AC;˘ Problem: much of the research has focused on substance abuse populations, not on long term opioid use for chronic pain

Teratogenic risks17 â&#x20AC;˘ Cardiac defects

Additional Neonatal Risks17-18 • Low birth weight • Premature birth • Hypoxic-ischemic brain injury • Prolonged QT syndrome • Neonatal withdrawal • Neonatal death Also: Breastfeeding19

Sleep Risks • Disrupted Sleep Architecture20 • Central Sleep Apnea21 Disturbed sleep may worsen pain and may promote pain pathophysiology.

Opioid Bowel Dysfunction â&#x20AC;˘ Risk for OBD increases with during of opioid use.22

Tolerance & Opioid-Induced Hyperalgesia â&#x20AC;˘ Tolerance: the requirement for a higher dose to maintain effect â&#x20AC;˘ Hyperalgesia: increased pain from a stimulus that normally provokes pain

Risks for Older Persons â&#x20AC;˘ Falls and fractures23-24

Poisoning/Unintentional Overdose • Higher doses of opioids are strongly associated with increased risk for overdose for both sexes25-27 Unintentional overdose    

Over-prescription Overuse Adverse effects Drug-drug interactions (polypharmacy)

Psychological/Behavioral Risks

Psychological/Behavioral Risks Psychological factors either predict or strongly associate with receipt of opioid prescription.28-31 Greater levels of psychopathology may associate with reduced opioid analgesia.31

• Depression • Anxiety

Definition of Pain â&#x20AC;&#x153;an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damageâ&#x20AC;?

--International Association for the Study of Pain

Risk:Benefit Analysis • There is a need for the prescribers to carefully weight risk:benefit ratio of opioids, particularly given that the efficacy of opioids in chronic pain is poor.

• Prescribers must discuss the efficacy data and the relevant risks/consequences with the patient prior to prescription.

• Prescribing for a 24 y.o. woman is different than prescribing for a 70 y.o. man.

If opioids donâ&#x20AC;&#x2122;t work well for most patients, what do we do?

Address the factors that influence the experience of pain

Factors that Influence Pain • • • •

Cognitive Emotional Behavioral (daily choices, self-care) Stress

Direct Patients To: • Work with a pain psychologist or “pain coach” • Learn a skill set to better manage stress and pain responses.

• Learn more about their daily stressors and how to manage them without medications.

• Learn which choices will decrease their pain and stress.

What Patients Need: â&#x20AC;˘ To make the relevant life changes that support reduced pain. â&#x20AC;˘ To learn how to keep pain controlled by using pain management skills. (both of these are best accomplished with support)

Why This Approach Works: • Patients become empowered to selfmanage their pain.

• Helplessness decreases.

• Anxiety decreases; mood and function improve.

• Opioid use decreases

As a Prescriberâ&#x20AC;Ś â&#x20AC;Śyou have a strong position of influence and can appropriately de-emphasize opioids and encourage behavioral care.

At a miminum, a behavioral approach will help reduce use of opioids.

Pain Psychologists • Employed at most academic pain clinics • Search state psychological association (search for pain or health specialization) • Google “Pain Psychologist” in the patient’s home town • Direct patients to online and print resources

Resources • “Managing Pain Before it Manages You” - Margaret Caudill, MD • Pain management skills audio CDs (Many are available commercially. Recommend your patients find and use one they like).

~ Thank You ~

References Darnall BD, Stacey BR, Chou R. Medical and psychological risks and consequences of long-term opioid therapy in women. Pain Med. Sept 2012.

Darnall BD, Stacey, B.R. Sex differences examined in long-term opioid use: Cautionary notes for prescribing in women. Archives of Internal Medicine. 2012;172(5):431-432).

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