Urine Drug Testing by PAINWeek

Urine Drug Testing Paul J. Christo, MD, MBA

Disclosure ď&#x201A;§Consultant/Independent Contractor: Ameritox, Actavis, Chattem, Inc., Quadrant HealthCom Inc., Perrigo Company ď&#x201A;§Grant/Research Support: Medtronic

Learning Objectives Describe the value of urine drug monitoring in the context of opioid therapy Summarize the limitations of urine drug monitoring for opioid therapy Discuss when to test and the basics of interpreting urine test results

Opioids for Chronic Non-CA Pain  Use has increased over 222% from 1980-2002  Associated increase in abuse and diversion – Drug Abuse Warning Network (DAWN) reports over 400,000 ED visits due to opioid use

 Urine drug monitoring (UDM) a unique tool to monitor abuse, misuse, and opioid diversion – Use low, though among primary care doctors – More routine among pain specialists Kuehn BM. Opioid prescriptions soar: Increase in legitimate use as well as abuse. JAMA 2007;297(3):249-51 Substance Abuse and Mental Health Services Administration (SAMHSA). Drug Abuse Warning Network (DAWN). 2009. Available at: https: dawninfo.samhsa.gov/default.asp (accessed January 2011)

Rationale for UDM  Incomplete evidence for UDM preventing opioid misuse – Weak evidence, but theoretical value

 Several medical societies and state medical boards support its use (theoretical benefits) – APS, AAPM

 Some estimates that opioid abuse 18-41% for chronic pain patients  Adherence monitoring decreases controlled substance abuse & illicit drug use

Federation of State Medical Boards of the United States, Inc. Model policy for the use of controlled substances for the treatment of pain. J Pain Palliat Care Pharmacother 2005;19(2):73-8 Chou R, Fanciullo GJ, Fine PG, et al. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain 2009;10(2):113-30 Christo PJ, Manchikanti LM, Ruan X, Bottros M, Hansen H, Solanki DR, Jordan AE, Colson J: Urine Drug Testing in Chronic Pain. Pain Physician 2011; 14:123-143.

Rationale for UDM  Drug diversion of interest to regulators and physicians – Majority of drugs from a single physician’s prescription & family members share it

 Difficult to predict likelihood of opioid abuse – Past or current H/O substance abuse, family H/O substance abuse, smoking history, anxiety, depression, personality disorders can increase probability • Not solely predictive, though

– Risk stratification useful, but no patient at zero risk of opioid abuse

Christo PJ, Manchikanti LM, Ruan X, Bottros M, Hansen H, Solanki DR, Jordan AE, Colson J: Urine Drug Testing in Chronic Pain. Pain Physician 2011; 14:123-143. Peppin JF, Passik SD, Couto JE, Fine PG, Christo PJ, Argoff D, Aronoff GM, Bennett D, Cheatle MD, Slevin KA, Goldfarb NI: Recommendations for Urine Drug Monitoring as a Component of Opioid Therapy in the Treatment of Chronic Pain. Pain Medicine 2012 [epub ahead of print] Fishbain DA, Cole B, Lewis J, et al. What percentage of chronic nonmalignant pain patients exposed to chronic opioid analgesic therapy develop abuse/addiction and /or aberrant drug-related behaviors? A structured evidence-based review. Pain Med 2008;9(4):444-59

Substance Use Assessment Ask about present or past use of licit and illicit drugs H/O illicit drug use may complicate opioid therapy –Not a contraindication to opioid use, but untreated addiction not consistent with successful treatment of chronic pain

If unwilling to go to specialists, or opposed to UDM consider waiting to initiate opioids or discontinue current therapy Gourlay DL, Heit HA, Almahrezi A. Universal precautions in pain medicine: A rational approach to the treatment of chronic pain. Pain Med 2005;6(2):107-12

Screening  Strong recommendation to test all patients prescribed short or long acting opioids for long term pain control – Why: difficult to identify drug use behavior with subjective data – Long term: greater than 3 months of opioid therapy

 In conjunction with H & P, psychological screens  Initiate thorough treatment plan with multimodal therapies  Monitoring important for patient safety, decision making, objectivity in delivering care Christo PJ, Manchikanti LM, Ruan X, Bottros M, Hansen H, Solanki DR, Jordan AE, Colson J: Urine Drug Testing in Chronic Pain. Pain Physician 2011; 14:123-143. Gourlay DL, Heit HA, Almahrezi A. Universal precautions in pain medicine: A rational approach to the treatment of chronic pain. Pain Med 2005;6(2):107-12 Peppin JF, Passik SD, Couto JE, Fine PG, Christo PJ, Argoff D, Aronoff GM, Bennett D, Cheatle MD, Slevin KA, Goldfarb NI: Recommendations for Urine Drug Monitoring as a Component of Opioid Therapy in the Treatment of Chronic Pain. Pain Medicine 2012 [epub ahead of print]

Compliance Monitoring  Present UDM as routine aspect of care, like HbA1C testing for diabetes management – Assesses adherence to treatment – Non confrontational

 Make clear at first office visit

– Policy, purpose, how results used

 Consider standard written agreement

– (www.partnersagainstpain.com/printouts/A7012CT6.pdf) – Outlines responsibilities of practitioner and patient – Sign at initial visit, copies given to patient, pharmacy, primary care doctor Gourlay DL, Heit HA, Almahrezi A. Universal precautions in pain medicine: A rational approach to the treatment of chronic pain. Pain Med 2005;6(2):107-12 Peppin JF, Passik SD, Couto JE, Fine PG, Christo PJ, Argoff D, Aronoff GM, Bennett D, Cheatle MD, Slevin KA, Goldfarb NI: Recommendations for Urine Drug Monitoring as a Component of Opioid Therapy in the Treatment of Chronic Pain. Pain Medicine 2012 [epub ahead of print]

Urine Monitoring  Many biological specimens available for drug testing – Urine, blood, sweat, hair, saliva, nails  Urine preferred cause can detect presence or absence of drugs with good specificity, sensitivity, relative ease of administration, and lower cost – Detection time for most drugs or metabolites usu. 1-3 days

 Prime purposes of UDM – Ensure compliance with prescribed opioid regimen – Monitor use of non-prescribed or illicit substances

Manchikanti L, Malla Y, Wargo B, et al. Protocol for accuracy of point of care or in-office urine drug testing (immunoassay) in chronic pain patients: A prospective analysis of immunoassay and liquid chromatography tandem mass spectroscopy (LC/MS/MS). Pain Physician 2010;13:E1-E22 Cone EJ, Caplan YH, Black DL, et al. Urine drug testing of chronic pain patients: Licit and illicit drug patterns. J Anal Toxicol 2008;32:530-543

How to Test: Strategies  Comprehensive urine drug test – Ilicit drugs, commonly prescribed opioids, other prescription drugs of potential abuse (benzo, barbiturates, carisoprodol, tramadol)

 Routine screening panel tests for: – Cocaine, amphetamine, opioids, methadone, marijuana, benzodiazepines

 Ideally, preliminary results available same day – If not, limit dose or days, or delay opioid til results available Peppin JF, Passik SD, Couto JE, Fine PG, Christo PJ, Argoff D, Aronoff GM, Bennett D, Cheatle MD, Slevin KA, Goldfarb NI: Recommendations for Urine Drug Monitoring as a Component of Opioid Therapy in the Treatment of Chronic Pain. Pain Medicine 2012 [epub ahead of print] Heit HA, Gourlay DL. Urine drug testing in pain medicine. J Pain Symptom Manage 2004;27(3):260-7

How to Test: Overview  Initial testing done with class-specific immunoassay drug panels – Typically do not identify individual drugs within a class

 Followed by a technique such as GC/MS – To identify or confirm the presence or absence of a specific drug and/or its metabolites

Heit HA, Gourlay D. J Pain Sympt Manage. 2004:27:260-267.

How to Test: Strategies  Immunoassay – Point of Care Testing (POC) – in office – Send to laboratory

 Specific drug identification – Gas chromatography/mass spectrometry (GC/MS) – Liquid chromatography tandem mass spectrometry (LC/MS/MS) – High performance liquid chromatography (HPLC)

Christo PJ, Manchikanti LM, Ruan X, Bottros M, Hansen H, Solanki DR, Jordan AE, Colson J: Urine Drug Testing in Chronic Pain. Pain Physician 2011; 14:123-143. Peppin JF, Passik

How to Test: Immunoassay  Immunoassay

– Frequently used as initial evaluation for testing – Tests numerous drugs or drug classes – Determines whether substance present or absent • Not detect the concentration of a drug/metabolite

– Testing for natural opioids very responsive to morphine and codeine, but can’t distinguish between them – Adequately (usually highly) sensitive, but not specific • Difficult to identify specific analyte • Can result in false negatives: miss oxycodone, methadone, fentanyl, for instance

– False positives can occur from cross reactivity with other substances • Methadone cross reacts with propoxyphene, seroquel • Amphetamine cross reacts with Vicks Vapor Spray, trazodone, ranitidine

Heit HA, Gourlay DL. Urine drug testing in pain medicine. J Pain Symptom Manage 2004;27(3):260-7 Christo PJ, Manchikanti LM, Ruan X, Bottros M, Hansen H, Solanki DR, Jordan AE, Colson J: Urine Drug Testing in Chronic Pain. Pain Physician 2011; 14:123-143. Katz N, Fanciullo GJ. Role of urine toxicology testing in the management of chronic opioid therapy. Clin J Pain 2002;18:S76-L82 Peppin JF, Passik

Drug Cross-Reactants

How to Test: Point of Care (POC)  POC urine testing – Screening in physician’s office – Dipstick immunoassay test – Low cost to evaluate presence of illicit substances primarily & recent controlled substance prescription medication – High sensitivity & low specificity – Make sure system used compliant with Clinical Laboratory Investigative Association Committee (CLIAC) Christo PJ, Manchikanti LM, Ruan X, Bottros M, Hansen H, Solanki DR, Jordan AE, Colson J: Urine Drug Testing in Chronic Pain. Pain Physician 2011; 14:123-143.

How to Test: Point of Care (POC) (cont’d)  POC urine testing – Inconsistent findings with therapy, send urine sample for quantitative evaluation – Current POC tests recommend gas chromatography/mass spectrometry (GC/MS) to confirm preliminary results – Insufficient to rely on POC to monitor therapy due to lower specificity – Can warn of actual or potential abuse and deter drug seeking patients

iScreen. One step drug screen test card (urine) [package insert]. Norfolk, VA: Instant Technologies, Inc. 2006 Peppin JF, Passik SD, Couto JE, Fine PG, Christo PJ, Argoff D, Aronoff GM, Bennett D, Cheatle MD, Slevin KA, Goldfarb NI: Recommendations for Urine Drug Monitoring as a Component of Opioid Therapy in the Treatment of Chronic Pain. Pain Medicine 2012 [epub ahead of print]

POC Testing Devices POC Testing Devices

How to Test: Specific Drug ID  Specific drug identification – Confirmatory testing (GC/MS, etc) required after immunoassay for high sensitivity and specificity – Necessary to identify which member of the detected class (opioid, benzodiazepine) responsible for the positive screen – Need to list specific names of drugs prescribed to patient – Need to know metabolites of prescribed opioids and illicit ones (heroin) to interpret results – Recent drug-specific immunoassay tests developed for oxycodone and methadone, though Heit HA, Gourlay DL. Urine drug testing in pain medicine. J Pain Symptom Manage 2004;27(3):260-7 Christo PJ, Manchikanti LM, Ruan X, Bottros M, Hansen H, Solanki DR, Jordan AE, Colson J: Urine Drug Testing in Chronic Pain. Pain Physician 2011; 14:123-143.

Confirmatory Test Report

How to Test: Review  Opioid immunoassays detect morphine and codeine – Do not detect synthetic opioids • Methadone • Fentanyl

– Do not reliably detect semisynthetic opioids • Oxycodone • Hydrocodone • Buprenorphine • Hydromorphone

 GC/MS will identify these medications Heit HA, Gourlay D. J Pain Sympt Manage. 2004:27:260-267.

How to Test: Urine Sample  Measure temperature and specific gravity, urinary creatinine, pH

– Assists with results interpretation – Collection cups have temperature gauge; SG, creatinine, pH reported by labs – Precautions to reduce risk of tampering or substitution – Temperature • Should fall within range of 90° F to 100° F by 4 minutes of voiding

– pH

• Fluctuates but usually in range of 4.5-8.0

– Creatinine • • • •

Varies with water intake and hydration 20 mg/dL – normal human urine <20 mg/dL – dilute < 5 mg/dL – not consistent with human urine

Heit HA, Gourlay DL. Urine drug testing in pain medicine. J Pain Symptom Manage 2004;27(3):260-7 Fraser AD, Zamecnik J. Impact of lowering the screening and confirmation cutoff values for urine drug testing based on dilution indicators. Ther Drug Monit 2003;25(6):723-7 Peppin JF, Passik SD, Couto JE, Fine PG, Christo PJ, Argoff D, Aronoff GM, Bennett D, Cheatle MD, Slevin KA, Goldfarb NI: Recommendations for Urine Drug Monitoring as a Component of Opioid Therapy in the Treatment of Chronic Pain. Pain Medicine 2012 [epub ahead of print]

Urine Retention Times – Be aware of drug retention times for drug classes – These are windows of detection for drugs – Represents how long after drug administration a patient continue to excrete that drug and/or metabolite above a specific test cutoff level – Detection time of most drugs or metabolites in urine: 1-3 days – Examples

Amphetamines – 48 hrs Opioids – 2 to 3 days Benzodiazepines - 3 days up to 4-6 weeks Heroin metabolite (6 acetyl morphine) < 12 hrs; Cocaine metabolite (benzoylecgonine) – 13 days • Phencyclidine – 2-7 days if casual use; up to 30 days for chronic use • Chronic use of lipid-soluble drug (marijuana use) – can extend window a week or more and up to 30 days for chronic use • • • •

Heit HA, Gourlay DL. Urine drug testing in pain medicine. J Pain Symptom Manage 2004;27(3):260-7 Vandevenne M, Vandenbussche H, Verstraete A. Detection time of drugs of abuse in urine. Acta Clinica Belgica 2000;55:323-333

Drug Metabolism  Be aware of metabolites for results interpretation  Opioids – Oxycodone – Codeine – Codeine – Morphine – Morphine – Heroin

 Cocaine  Heroin

oxymorphone morphine primarily hydrocodone hydromorphone morphine 3 glucuronide and morphine 6 glucuronide hydromorphone (small pathway) morphine and 6 MAM (monoacetylmorphine)

benzoylecgonine 6 acetyl morphine

Heit HA, Gourlay DL. Urine drug testing in pain medicine. J Pain Symptom Manage 2004;27(3):260-7 Peppin JF, Passik SD, Couto JE, Fine PG, Christo PJ, Argoff D, Aronoff GM, Bennett D, Cheatle MD, Slevin KA, Goldfarb NI: Recommendations for Urine Drug Monitoring as a Component of Opioid Therapy in the Treatment of Chronic Pain. Pain Medicine 2012 [epub ahead of print] Christo PJ, Manchikanti LM, Ruan X, Bottros M, Hansen H, Solanki DR, Jordan AE, Colson J: Urine Drug Testing in Chronic Pain. Pain Physician 2011; 14:123-143.

Metabolism of Commonly Prescribed Opioids

Figure 2. Peppin JF, Passik SD, Couto JE, Fine PG, Christo PJ, Argoff D, Aronoff GM, Bennett D, Cheatle MD, Slevin KA, Goldfarb NI: Recommendations for Urine Drug Monitoring as a Component of Opioid Therapy in the Treatment of Chronic Pain. Pain Medicine 2012 [epub ahead of print]

Testing Limitations  Several pharmacological principles can affect UDT findings  Cutoff Selection

– Any sample having drug concentration ≥ certain level considered “positive” – Screening and confirmatory cutoff concentrations variable for certain drugs like amphetamines, cocaine, opioids, amphetamine, etc – Lower cutoff permits longer detection time, increases sensitivity, but also potential for false-positive results

 Pharmacokinetics, Pharmacodynamics, Pharmacogenetics

– Opioids given by different routes (oral, transdermal, intrathecal) have variable pharmacokinetics – Pharmacokinetic profile influenced to environmental and genetic factors – Pharmacodynamic variability poorly understood Nafzinger AN, Bertino JS. Utility and application of urine drug testing in chronic pain management with opioids. Clin J Pain 2009;25:73-79 Christo PJ, Manchikanti LM, Ruan X, Bottros M, Hansen H, Solanki DR, Jordan AE, Colson J: Urine Drug Testing in Chronic Pain. Pain Physician 2011; 14:123-143. Nafziger AN, Bertino JS. Utility and application of urine drug testing in chronic pain management with opioids. Clin J Pain 2009;25:73-79

Testing Limitations (cont’d) – Absorption & Distribution • These vary, so similar doses not result in similar systemic exposure (drug concentration at the site of effect) – Morphine has 2.5 fold variability in absorption based on oral, buccal, sublingual, IM routes – First pass metabolism varies causing different amount of drug reaching systemic circulation – Transporters of drugs across intestine, hepatocyte, blood brain barrier may exhibit genetic polymorphism. » Can cause great variabiltly in drug absoption, distribution, and opioid efficacy.

– Metabolism, Transport, Receptor Affinity • Phase I (cytochrome p450) and Phase II (UDP-glucuronodation) enzymes • Both have genetic polymorphism poor, intermediate, extensive, normal, ultra-rapid metabolizers • Phase I: impact drug effect by determining how much of prodrug converted to active drug – E.g. codeine

morphine

Kim RB. Transporters and drug discovery: Why, when, and how. Mol Pharm 2006;3:26-32 Christo PJ, Manchikanti LM, Ruan X, Bottros M, Hansen H, Solanki DR, Jordan AE, Colson J: Urine Drug Testing in Chronic Pain. Pain Physician 2011; 14:123-143. Nafzinger AN, Bertino JS. Utility and application of urine drug testing in chronic pain management with opioids. Clin J Pain 2009;25:73-79 Christo PJ, Manchikanti LM, Ruan X, Bottros M, Hansen H, Solanki DR, Jordan AE, Colson J: Urine Drug Testing in Chronic Pain. Pain Physician 2011; 14:123-143. Nafziger AN, Bertino JS. Utility and application of urine drug testing in chronic pain management with opioids. Clin J Pain 2009;25:73-79

Testing Limitations (cont’d) Metabolism, Transport, Receptor Affinity –Phase 1: multiple cytochrome p450 enzymes metabolize opioids • Due to inter-individual genotypic variations, dose of drug might not correlate with extent of pain relief, or urine drug concentration

–Phase II: enzymes can affect metabolism of many opioids

Somogyi AA, Barratt DT, Coller JK. Pharmacogenetics of opioids. Clin Pharmacol Ther 2007;81:429-444 Christo PJ, Manchikanti LM, Ruan X, Bottros M, Hansen H, Solanki DR, Jordan AE, Colson J: Urine Drug Testing in Chronic Pain. Pain Physician 2011; 14:123-143.

Adulteration or Subversion of UDM  Modalities to defeat UDT

– Urinary dilution: dilution of sample to lower concentration of the drug in urine below level for test to be considered positive • High water intake or use of diuretics

– Urine substitution: purchase freeze dried clean urine to reconstitute • “Urinator” allows reconstitution and warm up to body temperature – Can be hidden in clothes

– In vitro adulterants

• “Urinaid”: contains glutaraldehyde which interferes with IA

– Niacin: Internet information says it can prevent detection of THC (marijuana) • No scientific evidence that niacin can alter urine test result, though

Wu AHB. Integrity of urine specimens submitted for toxicologic analysis: Adulteration, mechanisms of action, and laboratory detection. Forensic Sci Rev 1998;10:47-65 George S, Braithwaite RA. The effect of glutaraldehyde adulteration of urine on Syva EMITT II drugs of abuse assays. J Anal Toxicol 1996;20:195-196 Centers for Disease Control and Prevention (CDC). Use of niacin in attempts to defeat urine drug testing-five states, January-September 2006. MMWR Morb Mortal Wkly Rep 2007;56:365-366

When to Test  Initial test part of risk assessment & can help risk stratify – Performed at first visit

 Later tests represent ongoing monitoring based on initial risk level  Risk factors help determine follow up frequency

– Consider SOAPP-R (Screener and Opioid Assessment for People with Pain Revised) • Assigns patients to low, medium, high risk categories

– Use other strategies as well for risk assessment

• PMH, H/O prior opioid use and known misuse, H/O psychiatric diagnoses predisposing to abuse

 Procedure for periodic UDM

– Draw from a hat, flip a coin, roll a die at each visit to see if tested that visit – Impart fairness and help prevent anticipating time of testing

 Recommendations for frequency of testing

– Low risk of misuse – Periodically eligible for test at each visit • Minimum of one test every 6 months • POC – one GC/MS or LC/MS/MS test yearly

When to Test (cont’d)  Recommendations for frequency of testing

– Medium to high risk – Periodically eligible for test at each visit • Minimum of one test every 3 months • POC – one GC/MS or LC/MS/MS test every 6 months

 Periodically reassess risk

– If exhibit behavior of opioid misuse, test if concern arises – If suspected of abusing other substances or diverting, may undergo more frequent GC/MS testing • Strongly consider co-management by specialist in substance abuse • Use pill counts and Prescription Monitoring Programs when possible, especially in mediumhigh risk patients

 State requirements for monitoring

– May have mandate for testing schedules Peppin JF, Passik SD, Couto JE, Fine PG, Christo PJ, Argoff D, Aronoff GM, Bennett D, Cheatle MD, Slevin KA, Goldfarb NI: Recommendations for Urine Drug Monitoring as a Component of Opioid Therapy in the Treatment of Chronic Pain. Pain Medicine 2012 [epub ahead of print]

Results Interpretation  Finding illicit drugs or non-prescribed medications

– Poses health risk and disrupts trust – Ongoing prescription of controlled substances with concurrent illicit drug use poses legal, ethical, regulatory risk for prescriber

 Categories of Concern

– Prescribed drug not detected – Illicit drug detected – Non-prescribed scheduled drug detected

 Prescribed Drug Not Detected

– Consider: Diversion, Hoarding, Not taking med,. Lab error, Self-escalating, Binge use, Timing of urine in relation to most recent dose (urine retention time), Taking medicine occasionally and not as prescribed, Rapid metabolism (rare), Drug-drug interaction – GC/MS test to confirm absence – Immediate action if absence of prescribed drug + illicit drug or non-prescribed scheduled drug Peppin JF, Passik SD, Couto JE, Fine PG, Christo PJ, Argoff D, Aronoff GM, Bennett D, Cheatle MD, Slevin KA, Goldfarb NI: Recommendations for Urine Drug Monitoring as a Component of Opioid Therapy in the Treatment of Chronic Pain. Pain Medicine 2012 [epub ahead of print] Gourlay DL, Heit HA, Almahrezi A. Universal precautions in pain medicine: A rational approach to the treatment of chronic pain. Pain Med 2005;6(2):107-12

Results Interpretation (cont’d)  Illicit Drug Detected

– Consider: Deliberate use of the drug, Addiction, Seeking more pain relief, False positive/lab error, Self medication, Exchanging prescribed drug for illicit one or other goods/services – False positive/Lab error • • • •

Refer to tables of known agents that interfere with urine tests (IA) Confirmatory tests (GC/MS) reduce interference significantly Discuss degree of interference with test vendor Examples – Poppy seeds, zolpidem, verapamil can interfere with opioids – NSAIDS, hemp seed can interfere with marijuana – Coca leaf tea, salicylates can interefere with cocaine – Ranitidine, typical antipsychotics can interfere with amphetamine – NSAIDS, sertraline can interfere with benzodiazepine

Peppin JF, Passik SD, Couto JE, Fine PG, Christo PJ, Argoff D, Aronoff GM, Bennett D, Cheatle MD, Slevin KA, Goldfarb NI: Recommendations for Urine Drug Monitoring as a Component of Opioid Therapy in the Treatment of Chronic Pain. Pain Medicine 2012 [epub ahead of print] Moeller KE, Lee KC, Kissack JC. Urine drug screening: Practical guide for clinicians. Mayo Clin Proc 2008;83(1):66-76

Results Interpretation (cont’d)  Non-prescribed Scheduled Drug is Detected – Consider:

• Multiple prescribers: use PMP to help with who’s prescribing and whether prescribed legitimately • Metabolites: use table to help with metabolites of commonly prescribed opioids – Peppin JF et al, 2012 Pain Medicine and Christo PJ et al, 2011Pain Physician

 Extrapolation

– Amount of drug/metabolite in urine (ng/ml) shouldn’t be used to determine compliance with prescribed medication – Software and laboratory techniques not scientifically validated to to provide this information yet Gourlay DL, Heit HA. Compliance Monitoring in Chronic Pain Management. In: Bonica’s Management of Pain, 4th edition. Fishman, Ballantyne, Rathmell (eds). 2010 Nafzinger AN, Bertino JS. Utility and application of urine drug testing in chronic pain management with opioids. Clin J Pain 2009;25:73-79 Peppin JF, Passik SD, Couto JE, Fine PG, Christo PJ, Argoff D, Aronoff GM, Bennett D, Cheatle MD, Slevin KA, Goldfarb NI: Recommendations for Urine Drug Monitoring as a Component of Opioid Therapy in the Treatment of Chronic Pain. Pain Medicine 2012 [epub ahead of print]

Potential Differential Diagnoses Based on UDM Results

Table 1. Peppin JF, Passik SD, Couto JE, Fine PG, Christo PJ, Argoff D, Aronoff GM, Bennett D, Cheatle MD, Slevin KA, Goldfarb NI: Recommendations for Urine Drug Monitoring as a Component of Opioid Therapy in the Treatment of Chronic Pain. Pain Medicine 2012 [epub ahead of print]

Test Result Discrepancies  Suggested Actions based on Findings

– Verify lab results – Document findings and schedule follow up visit – Meet with patient & discuss findings in non-accusatory way • Is there an explanation? • Does explanation match or contradict results?

– Review treatment agreement – Counsel – Consider re-testing or additional testing

 If Misuse/Abuse Suspected

– Maintain or change therapy, and document reasons – Have protocol for patient discharge

• Written notification, efforts to refer patient to another physician or chemical dependency treatment, instructions on obtaining medical care • Consult state medical boards if can offer guidance on discharging patients • Alert patient’s other physicians/specialists

Test Result Discrepancies (cont’d)  If Diversion Suspected

– Discussion with patient and third party (nurse) – Limit supply, select drug with lower street value, more frequent visits, more frequent UDM, consult substance abuse specialist (five S’s) – Confirmed diversion • Discontinue opioid and notify authorities if criminal activity involved • Criminal behavior – altering, forging, stolen prescriptions, confirmed shopping • Federal statutes – clinician not legally obliged to notify law enforcement – State laws vary

• Social responsibilities – patient likely to obtain opioids from somebody else and continue to divert

 If Addiction Suspected – – – –

Co-manage with substance abuse specialist Decide to continue or discontinue opioid Apply 5 S’s Addiction medicine referral or 12 step program • Confirm participation in program • Collaborate with addiction medicine specialist

Peppin JF, Passik SD, Couto JE, Fine PG, Christo PJ, Argoff D, Aronoff GM, Bennett D, Cheatle MD, Slevin KA, Goldfarb NI: Recommendations for Urine Drug Monitoring as a Component of Opioid Therapy in the Treatment of Chronic Pain. Pain Medicine 2012 [epub ahead of print] Passik SD, Kirsh KL.Opioid therapy in patients with a history of substance abuse. CNS Drugs 2004;18(1):13-25

Test Result Discrepancies (cont’d)  Not taking Opioid as Prescribed – Dialogue with patient – Educate on safe and proper use – Emphasize initial agreement and rules – Change formulation

Cost  Office test + confirmatory test = $250 - $1,400  CMS changed UDT code in 2010 that excludes chromatography – Includes IA only in the office

 Weigh the costs of testing versus not testing  Balance medical-legal risks and ethical risks  Consider costs of periodic testing with benefit of surveillance on health system and society Christo PJ, Manchikanti LM, Ruan X, Bottros M, Hansen H, Solanki DR, Jordan AE, Colson J: Urine Drug Testing in Chronic Pain. Pain Physician 2011; 14:123-143. Peppin JF, Passik SD, Couto JE, Fine PG, Christo PJ, Argoff D, Aronoff GM, Bennett D, Cheatle MD, Slevin KA, Goldfarb NI: Recommendations for Urine Drug Monitoring as a Component of Opioid Therapy in the Treatment of Chronic Pain. Pain Medicine 2012 [epub ahead of print]

Summary  UDM has a role in treatment of patients using opioids for chronic pain  Medical societies and state boards support UDM as component of chronic pain management  More use among pain specialists, but lags among primary care doctors  Role of UDM – Protect patients – Protect clinicians – Protect access to opioids – Protect community

Adams NJ, Plane MB, Fleming MF, et al. Opioids and the treatment of chronic pain in a primary care sample. J Pain Symptom Manage 2001;22(3):791-6 Peppin JF, Passik SD, Couto JE, Fine PG, Christo PJ, Argoff D, Aronoff GM, Bennett D, Cheatle MD, Slevin KA, Goldfarb NI: Recommendations for Urine Drug Monitoring as a Component of Opioid Therapy in the Treatment of Chronic Pain. Pain Medicine 2012 [epub ahead of print]