Advanced MAT Implementation: - PowerPoint Presentation

Advanced MAT Implementation:Compliance Testing and Addressing Recurring Opioid Use and Polysubstance Use Copyright 2019, University of Pittsburgh. All Rights Reserved. Julie Kmiec, DO Assistant Professor and Addition Psychiatrist Western Psychiatric Institute and Clinic University of Pittsburgh Medical Center

Educational Objectives Review the purpose of toxicology testing; Discuss the types of toxicology testing and confirmatory testing; Present clinical cases to illustrate the use of urine toxicology testing in the treatment of opioid use disorder (OUD);Understand false positives, true positives, substituted urines, and metabolites.Know strategies for addressing recurring opioid use and polysubstance use.Know strategies to help ensure medication adherence. Copyright 2019, University of Pittsburgh. All Rights Reserved. RAMP

Testing patient’s urine who are enrolled in substance use disorder (SUD) treatment can allow the provider to: Ensure the patient is taking the prescribed medication; and Ensure the patient is not using any other substances. Provider warning:Testing a patient’s urine will not tell the medical provider how adherent someone is being to their medication.Studies show that treatment participants underreport drug use when compared with urine toxicology results. Purpose of Toxicology Testing 1-6 Copyright 2019, University of Pittsburgh. All Rights Reserved. RAMP Chermack, S. T., et al. (2000). "Comparison of patient self-reports and urinalysis results obtained under naturalistic methadone treatment conditions." Drug Alcohol Depend 59 (1): 43-49. Digiusto , E., et al. (1996). "Concordance between urinalysis results and self-reported drug use by applicants for methadone maintenance in Australia." Addict Behav 21 (3): 319-329. Hilario, E. Y., et al. (2015). "Denial of urinalysis-confirmed opioid use in prescription opioid dependence." J Subst Abuse Treat 48 (1): 85-90. Malbergier , A., et al. (2012). "Monitoring drug use among HIV/AIDS patients in Brazil: should we combine self-report and urinalysis?" Curr HIV Res 10 (8): 708-712. Myrick, H., et al. (2002). "Clinical characteristics of under-reporters on urine drug screens in a cocaine treatment study." Am J Addict 11 (4): 255-261. Yonkers, K. A., et al. (2011). "Self-report of illicit substance use versus urine toxicology results from at-risk pregnant women." J Subst Use 16 (5): 372-389.

Window of Detection Time Copyright 2019, University of Pittsburgh. All Rights Reserved. RAMP

Toxicology Testing Methods Test Type AdvantagesDisadvantagesUrineCommon testDone by several labsLong detection timeTests for several drugs Invasive when observed Can be substituted or adulterated even when observed“Shy bladder” or other prostate problemsOral FluidLess invasive testEasy to directly observeBetter suited for detecting parent drugShorter window of detectionOnly done by certain labsDry mouthBloodAlways directly observed Difficult to adulterate/substitute Venipuncture is necessary Very short detection timeUsually shows a parent drugExpensiveNot commonly used unless testing for alcohol Hair and NailsLong detection timeDirectly observedNoninvasiveDifficult to substitute sampleNot commonly available Difficult to interpret resultsCan’t detect use in the last 7-10 daysPatient may shave or trim hair and nails to avoid testingSweatCan detect recent use with a single sweat swipeCan detect cumulative use with a patch worn for a week Noninvasive Not commonly available Fewer drugs available to test Patient may remove sweat patch Limited quantity of sample for a confirmatory test Copyright 2019, University of Pittsburgh. All Rights Reserved. RAMP

Immunoassay Drug Screening Tests Immunoassay screening tests are: Mediated by enzyme antibody-antigen immunoassays; The most common type of screening test;Inexpensive;Able to provide rapid results;Able to provide accurate results; Similar in process for enzyme multiplied immunoassay technique (EMIT), enzyme linked immunosorbent assay (ELISA), and cloned enzyme donor immunoassay (CEDIA) assays; and Are able to be read at the point of care or a laboratory. IDDATE Copyright 2019, University of Pittsburgh. All Rights Reserved. RAMP

What Does a Negative Test Mean? A drug screen can be interpreted as negative when: There is no drug in the specimen; There is a drug in the specimen, but at a concentration below the detection threshold;There is a drug in the specimen at a concentration above the threshold, but the assay reacts only weakly with the particular drug that is present;There is interference with the assay, created by administration of other medications or by addition of adulterants;The sample was substituted; or There is a lab error. Copyright 2019, University of Pittsburgh. All Rights Reserved. RAMP

Confirming Tests Confirming a toxicology test sample can be done using a gas chromatography mass spectrometry (GCMS) test or a liquid chromatography mass spectrometry (LCMS). GCMS LCMS/MS GC : separates and quantifies drug.MS: identifies drug.LC : separates each analyte. MS/MS : fragments the compounds and detects their mass to charge ratios, allowing identification of a compound.GCMS is considered the gold standard test because it is 99% sensitive and 99% specific. RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved.

Opiate Metabolism RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved. Reisfield , G. M., et al. (2007). "Rational use and interpretation of urine drug testing in chronic opioid therapy." Ann Clin Lab Sci 37(4): 301-314.

Case One: Jonathon Date MethadoneAmphBarb Benzos Cocaine THCOpiateBupOxyNotes3/13/19+ + -Observed test Bup/Norbup : Negative+Opiate: morphine 3/6/19+++Bup/Norbup: >2000/6+Opiate: morphine and 6-MAM 2/27/19 + + + Bup / NorBup : Negative +Opiate: +6-MAM 2/20/19 + + + Bup / NorBup : 32/152 +Opiate: +6-MAM 2/6/19 + + + + Bup / NorBup : 72/243 +Opiate: hydromorphone and morphine 1/6/19 + + Bup / Norbup : Negative +Opiate: hydromorphone and morphine 12/16/18 + + + +Opiate: codeine, morphine 12/1/18 + + RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved.

Case One: Jonathon RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved. Subjects given one dose of buprenorphine Kronstrand R, Nyström I, Andersson M, et al. Urinary Detection Times and Metabolite/Parent Compound Ratios After a Single Dose of Buprenorphine. Journal of Analytical Toxicology 2008; 32(8):586-93 doi: 10.1093/jat/32.8.586.

Case One: JonathonSplit in half Case of patient withdrawing from buprenorphine Case of patient withdrawing from buprenorphine with relapse RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved. Vincent F, Bessard J, Vacheron ,J Mallaret M, Bessard G. Determination of buprenorphine and norbuprenorphine in urine and hair by gas chromatography-mass spectrometry. J Anal Toxicol. 1999 Jul-Aug;23(4):270-9.

Opiate and Opioid Metabolism RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved.

Case Two: Tiffany Date Self Report UseBup / NorBupOxycodoneNoroxycodone Oxymorphone Hydrocodone HydromorphoneNorhydrocodone4/13/19X59/529++ 4/20/19 427/1920 + 4/27/19124/841 5/4/19 X 792/>2000 + + 5/11/19 108/691 5/18/19 379/1220 5/25/19 X 632/>2000 + + + RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved.

Is it Noroxymorphone or Nornaloxone?Data suggest that in the absence of parent drug concentrations of noroxymorphone/nornaloxone <75ng/mL are most likely to be associated with the metabolism of naloxone rather than an oxycodone or oxymorphone containing drug. Nornaloxone was more prevalent in samples with buprenorphine and metabolites than the parent drug. RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved. Marin, S. J., et al. ( n.d. ). "Is it Noroxymorphone or Nornaloxone , and Why Should You Care?".

Noroxymorphone is also a minor metabolite of naltrexone:Clinicians should be aware that individuals on oral naltrexone may experience a positive urine immunoassay result for oxycodone due metabolization into noroxymorphone . Clinicians are encouraged to carefully review the confirmatory test for metabolites present to determine whether or not the result was due to naltrexone metabolization or oxycodone use. RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved. Stanciu CN, Gnanasegaram S. Naltrexone and Its Noroxymorphone Minor Metabolite - A Case Report. J Psychoactive Drugs 2019:1-3 doi : 10.1080/02791072.2019.1649507.

Other Opioids and MetabolitesN H O O N N N O H-O Methadone/ EDDP Fentanyl Acetylfentanyl Carfentanil Tramadol/ O-desmethyltramadol RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved.

Poppy Seeds Poppy seeds are not the sole source of morphine/codeine if: The total morphine amount is greater than 5,000ng/mL; The total codeine is greater than 300ng/mL;The morphine to codeine ratio is less than 2; The total morphine amount is greater than 1,000 ng/mL without any codeine present; or 6-MAM is present . Poppy seeds contain small amounts of codeine and morphine that can read positive on a toxicology screen. RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved. Tenore PL. Advanced urine toxicology testing. J Addict Dis 2010; 29 (4):436-48 doi : 10.1080/10550887.2010.509277.

Benzodiazepine Metabolism RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved.

Case Three: Tina Date MethAmphBarb Benzos Coc OpsTHCBupOxyOther3/24/16 + Bup/NorBup: 342/1978 3/21/16+Bup/NorBup: 150/954 3/7/16 + Bup/NorBup: 1040/3200 2/21/16 + + 2/7/16 + + GCMS negative for benzo 1/31/16 + + 1/10/16 + + 1/3/16 + + + GCMS negative for benzo +Morphine 12/27/15 + + 12/20/15 + + GCMS negative for benzo 12/5/15 + + + 11/27/15 + + + RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved.

Sertraline Diazepam Sertraline Sertraline may provide a false positive read for benzodiazepines making it important to order a GCMS. RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved. Nasky KM, Cowan GL, Knittel DR. False-Positive Urine Screening for Benzodiazepines: An Association with Sertraline?: A Two-year Retrospective Chart Analysis. Psychiatry ( Edgmont). 2009 Jul;6(7):36-9.

Stimulants When testing for stimulants it is important to remember: Immunoassay tests are sufficient for cocaine; Amphetamines differ from methylphenidate used for treating ADHD; and Vicks Vapo-Inhaler (L-methamphetamine) may result in positive test for methamphetamine but will be negative for D-methamphetamine RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved. Crystal Methamphetamine N H CH 3 CH 3 Smith ML, Nichols DC, Underwood P, et al. Methamphetamine and amphetamine isomer concentrations in human urine following controlled Vicks VapoInhaler administration. J Anal Toxicol 2014; 38 (8):524-7 doi : 10.1093/ jat /bku077

Specimen Validity Tests Test Type Normal RangeAdulteration RangepH4.5-9< 3 or > 11 Creatinine ≥ 20Dilute if < 20Cr < 2 is not consistent with human urine.Specific Gravity1.002 to 1.020NitritesCould be positive in urine from food, cured meats, UTI, or contaminated water. 500 MCG/mL shows adulteration.200 MCG/mL shows invalid results. RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved.

Urine Sample Substitution Methods RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved.

Other Strategies RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved.

Case Four: Reggie Reggie is a 27 year old male who began Suboxone treatment in January 2013, his medical history includes: A positive urine for his first drug toxicology screen; and A series of subsequent urines only positive for buprenorphine (confirmation testing was not done).Reggie is meeting his requirements at the clinic but something doesn’t seem right. He gets urine testing done off-site at a local lab. You order an observed urine and note it is positive for buprenorphine. RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved.

Urine Toxicology Results Date Meth Amph Barb BenzosCocEtOHOpsTHCBupOther6/28/13 + Bup/NorBup:19300/71 6/26/13 + Bup/NorBup: >20,000/94 6/7/13 Test not performed, empty specimen 6/6/13 + Urine creatinine: 82 5/28/13 + 5/14/13 + Urine creatinine: 16 L 5/9/13 + 4/25/13 + 4/18/13 + 4/11/13 + 4/4/18 + 3/27/13 + 3/20/13 + 3/14/13 + 3/7/13 + 2/21/13 + 1. 6/7/13: Observed the patient on camera at clinic and they turned in an empty cup. 2. 6/16/13: Patient presented to ED and provider requested a random urine which he did not provide. 3. 6/28/13: Provider observed test on camera, stood outside door, and collected urine which was warm to touch 4. After 6/28/13 the patient no showed and transferred to a different treatment center RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved.

Urine Toxicology Results Distribution of urine creatinine values in 96 samples from 45 patients prescribed buprenorphine.  The norbuprenorphine-buprenorphine ratio in 174 urine samples from 70 patients prescribed buprenorphine. RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved. Hull MJ, Bierer MF, Griggs DA, Long WH, Nixon AL, Flood JG. Urinary buprenorphine concentrations in patients treated with suboxone as determined by liquid chromatography-mass spectrometry and CEDIA immunoassay. J Anal Toxicol. 2008 Sep;32(7):516-21.

<0.02 is specific, but not very sensitive. RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved. Subsequent Studies on Norbup:Bup Ratios: Interpreting Quantitative Urine Buprenorphine and Norbuprenorphine Levels in Office-based Clinical Practice. 1 Results: Specimens from patients who reported or were suspected of urine adulteration had significantly lower Norbup:Bup ratios (p=0.04) . Buprenorphine >=700ng/ml offered the best accuracy for discriminating between adulterated and non-adulterated specimens. High Prevalence of Urine Tampering in an Office-based Opioid Treatment Practice Detected by Evaluating the Norbuprenorphine to Buprenorphine Ratio.2Results: Norbup:Bup ratios less than 0.2 (rather than 0.02) may indicate the urine sample has been adulterated.Quantitative Testing of Buprenorphine and Norbuprenorphine to Identify Urine Sample Spiking During Office-based Opioid Treatment.3Results: All of the samples suspected of spiking contained buprenorphine levels greater than 2000 ng/mL , with a mean norbuprenorphine level of 11.9 ng/ mL. Donroe JH, Holt SR, O'Connor PG, Sukumar N, Tetrault JM. Interpreting quantitative urine buprenorphine and norbuprenorphine levels in office-based clinical practice. Drug and alcohol dependence 2017; 180 :46-51 doi : 10.1016/j.drugalcdep.2017.07.040 Accurso AJ, Lee JD, McNeely J. High prevalence of urine tampering in an office-based opioid treatment practice detected by evaluating the norbuprenorphine to buprenorphine ratio. Journal of substance abuse treatment 2017; 83 :62-67 doi : 10.1016/j.jsat.2017.10.002 Suzuki J, Zinser J, Issa M, Rodriguez C. Quantitative testing of buprenorphine and norbuprenorphine to identify urine sample spiking during office-based opioid treatment. Substance abuse 2017; 38 (4):504-07 doi : 10.1080/08897077.2017.1356796

Case Five: Charlotte Naloxone is only 2-10% bioavailable when administered sublingually. Date Observed MethadoneAmphBarb BenzosCocOps THCBup Oxy Other1/28/16 ++ 1/24/16 X + + Bup/NorBup: 267/1220 Naloxone: 22 1/21/16 + + Bup/NorBup: 19/217 Naloxone: 22 1/17/16 X + + + Bup/NorBup: 148/843 morphine & hydromorphone 1/16/16 X + + + Bup/NorBup: 292/823 morphine & hydromorphone 1/10/16 X Bup/NorBup: > 20,000/224 Naloxone: > 4,000 1/3/16 Bup/NorBup: > 20,000/68 Naloxone: > 4,000 12/30/15 Bup/NorBup: 20,000/129 12/20/15 + 12/13/15 + 12/6/15 + + 11/29/15 + + RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved. Harris DS, Jones RT, Welm S, Upton RA, Lin E, Mendelson J. Buprenorphine and naloxone co-administration in opiate-dependent patients stabilized on sublingual buprenorphine. Drug Alcohol Depend . 2000 Dec 22;61(1):85-94. PubMed PMID:11064186.

Comparing Adulterated and Authentic Samples RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved. Hull MJ, Bierer MF, Griggs DA, Long WH, Nixon AL, Flood JG. Urinary buprenorphine concentrations in patients treated with suboxone as determined by liquid chromatography-mass spectrometry and CEDIA immunoassay. J Anal Toxicol. 2008 Sep;32(7):516-21.

Case Six: Ricky Date Observed Meth Amph Barb BenzosCocEtOHOpsTHCBupOxyOther 5/26/17 + Bup/NorBup: 528/>2000 5/1/17 + Bup/NorBup: 304/1170 3/6/17 + Bup/NorBup:519/>2000 2/6/17 + Bup/NorBup: 796/>2000 1/9/17 + Bup/NorBup: 722>2000 9/19/16 + Bup/NorBup: 600/>2000 8/22/16 + Bup/NorBup: 646/1760 3/7/16 + Bup/NorBup: 533/1790 2/8/16 + Bup/NorBup: 528/1470 1/13/16 + Bup/NorBup: 323/788 Creatinine: 152.4 5/11/15 + Bup/NorBup: 486/2270 4/13/15 + + Bup/NorBup: 716/2230 3/16/15 + Bup/NorBup: 494/2030 2/16/15 + Bup/NorBup: 420/1650 1/20/15 + Bup/NorBup:624/2410 12/29/14 + Bup/NorBup:373/1030 RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved.

Can bup/norbup Levels Indicate Medication Misuse? RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved. Norbup to bup ratio <0.2 generally indicates medication has been dissolved in specimen1,2 : Bup and norbup can be detected in urine up to 96 hr. after dosing;Concentrations of norbup generally become higher than bup within a few hours after intake; and Norbup:bup ratios of less than 0.5 indicate very recent use.Some patients may have higher bup levels than norbup levels due to3:Lab procedures;Patient may be taking CYP 3A4 inhibitor which slows conversion to metabolite;Patient may be taking a medication which is a substrates of CYP 3A4 resulting in competition for the isoenzyme, thereby causing higher levels of bup; andPatient took dose shortly before urine test.Kronstrand R, Nyström I, Andersson M, et al. Urinary Detection Times and Metabolite/Parent Compound Ratios After a Single Dose of Buprenorphine. Journal of  Analytical Toxicology 2008; 32 (8):586-93 doi : 10.1093/ jat /32.8.586Accurso AJ, Lee JD, McNeely J. High prevalence of urine tampering in an office-based opioid treatment practice detected by evaluating the norbuprenorphine to buprenorphine ratio. Journal of substance abuse treatment 2017;83:62-67 doi: 10.1016/j.jsat.2017.10.002 Gervais JR, Hobbs GA. Use of an Acetyl Derivative to Improve GC-MS Determination of Norbuprenorphine in the Presence of High Concentrations of Buprenorphine in Urine. Journal of Analytical Toxicology 2016;40(3):208-12 doi : 10.1093/ jat /bkw001

Case Seven: Mac Date Meth Amph Barb BenzosCocEtOHOpsTHCBupOxyOther3/6/17 + + Bup/NorBup: >2000/>2000 2/27/17 + + Bup/NorBup: 647/1520 2/20/17 + + Bup/NorBup: 608/1890 2/13/17 Test not performed 2/6/17 + + Bup/NorBup: 625/>2000 1/30/17 + + Bup/NorBup: 793/873 12/28/16 + + Bup/NorBup: 889/>2000 10/20/16 + + Bup/NorBup: 735/>2000 10/13/16 + + Bup/NorBup: 1450/>2000 10/3/16 + + Bup/NorBup: 501/1430 9/28/16 + + Bup/NorBup: 1260/>2000 9/12/16 + + + Bup/NorBup: 1580/>2000 8/29/16 + + Bup/NorBup: 1510/>2000 8/22/16 + + Bup/NorBup: 372/916 8/15/16 + + Bup/NorBup: 1230/>2000 8/10/16 + + Bup/NorBup: 737/>2000 RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved.

Case Eight: Alex Date OBSBupNorbup CR Other 7/18/19372665.37/25/19 30 26 64.4 8/1/19372563.98/8/19X 21 147 59.9 Positive: Morphine 8/15/19 X 22 173 66.3 8/22/19 >2000 neg 87.2 10/3/19 X Positive: Morphine, codeine, hydromorphone, and hydroxyalprazolam RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved.

Storing Urine Creatinine has been shown to degrade as a function of time and temperature. 4 degrees Celsius 25 degrees Celsius 37 degrees Celsius 55 degrees Celsius RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved. Spierto, F. W., et al. (1997). "Stability of urine creatinine." Clin Chim Acta 264 (2): 227-232.

Case Ten: Robbie Robbie is a 45 year old obese woman with untreated diabetes and hypothyroidism who does not follow with primary care, her treatment history includes: Sublingual Suboxone 8/2mg daily;Regular adherence to treatment guidelines; andRepeated positive test for ethyl alcohol on urine toxicology test despite that she:Denies drinking; and Her ethyl glucuronide & ethyl sulfate alcohol tests are consistently negative . How do you explain this? RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved.

Alcohol Test Detection TimeSpecial CircumstancesBreathalyzerFluctuatesPatients may claim that they just used mouthwash but this is not a plausible possibility. Ethyl glucuronide and ethyl sulfate 4 daysThere may be a false positive result if a patient regularly uses hand sanitizer, but have changed detection limits to decrease this possibility.Phosphatidylethanol (PEth) test3 weeks Scores greater than 20ng/mL is considered evidence of moderate to severe drinking. Urine Test7-12 hoursN/A RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved.

Case Eleven: Ellie Date Meth Amph Barb BenzosCocEtOHOpsTHCBupOxyOther4/17/17 + Bup/NorBup: 30/464 4/10/17 Empty specimen cup 4/3/17 + + + Bup/NorBup: 91/381 Opioid: morphine & oxycodone 3/29/17 + + Bup/NorBup: 6/48 3/13/17 + + Bup/NorBup: 7/41 Opioid: morphine 3/6/17 Leaked in transit 2/27/17 + + + Bup/NorBup: 11/7 2/13/17 Leaked in transit 2/6/17 + Bup/NorBup: 195/576 1/13/17 + + + Bup/NorBup: 97/53 1/6/17 + + Bup/NorBup: >2000/16 12/30/16 + Bup/NorBup: >2000/5 12/16/16 Insufficient quantity 12/5/16 + + + Bup/NorBup: 28/82 11/28/16 + + + Bup/NorBup: 26/63 Opioid: morphine 11/15/16 + + + HCG negative RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved.

Case Twelve: Liz Date Bup/NorBupTHC/CRTHC Benzos CR 3/16/1919/270746373oxazepam54.4 3/23/19 170/1370 102 194oxazepam190.84/13/1983/252negneg 25.3 4/20/19 211/774 36 22 57.7 4/27/19 207/708 36 22 58.6 5/4/19 219/774 35 21 56 5/11/19 200/1380 84 93 clonazepam alprazolam 109.2 5/16/19 221/1150 137 124 clonazepam alprazolam 89.1 5/22/19 361/>2000 100 210 clonazepam alprazolam 207.3 RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved.

Strategies for Addressing Recurring Opioid Use and Polysubstance Use1-2 Encourage patient engagement with a case manager to improve social support and ensure connection to necessary treatments/services. Encourage patient engagement with psychosocial and recovery support services.Utilize motivational interviewing techniques to gain a deeper understanding of factors impacting the patient’s substance use and strengthen motivation and commitment to change.Discuss incremental behavior changes with patients to ensure changes are realistic and achievable. Discuss harm reduction strategies and additional treatment options with patients who continue to use opioids and/or other substances.Work with patients to develop a prevention plan that will help them better recognize triggers and take steps to prevent substance use. Update treatment plans as necessary (e.g. appointment schedule, prescription length, etc.)Copyright 2019, University of Pittsburgh. All Rights Reserved. RAMP Melemis SM. Relapse Prevention and the Five Rules of Recovery. Yale J Biol Med. 2015;88(3):325–332. Published 2015 Sep 3. Gorski, T., & Miller, M., Staying Sober: A Guide for Relapse Prevention: Independence Press, 1986

Strategies for Ensuring Medication AdherenceConduct scheduled and random urine drug tests. Conduct scheduled and random pill/film counts.For oral buprenorphine, conduct an observed dosing at the start of treatment to ensure the patient knows how to properly take medication. Copyright 2019, University of Pittsburgh. All Rights Reserved. RAMP

Conducting Oral Buprenorphine Pill/Film CountsPill Count: Ensure the remaining number of pills matches the expected number for taking medication as-prescribed. Ensure the medication brought in matches the prescribed medication.e.g. “AN 415” imprinted on generic bup/nx tablets. Film Count: Ensure the remaining number of films matches the expected number for taking the medication as-prescribedCheck the film lot numbers to see that they are the same.Ensure the film packets aren’t opened.Copyright 2019, University of Pittsburgh. All Rights Reserved. RAMP

Copyright 2019, University of Pittsburgh. All Rights Reserved.Thank you! Julie Kmiec, DO Assistant Professor and Addition PsychiatristWestern Psychiatric Institute and ClinicUniversity of Pittsburgh Medical Center

References Accurso AJ, Lee JD, McNeely J. High prevalence of urine tampering in an office-based opioid treatment practice detected by evaluating the norbuprenorphine to buprenorphine ratio. Journal of substance abuse treatment 2017;83:62-67 doi : 10.1016/j.jsat.2017.10.002Chermack, S. T., et al. (2000). "Comparison of patient self-reports and urinalysis results obtained under naturalistic methadone treatment conditions." Drug Alcohol Depend 59(1): 43-49.Digiusto, E., et al. (1996). "Concordance between urinalysis results and self-reported drug use by applicants for methadone maintenance in Australia." Addict Behav 21 (3): 319-329.Donroe JH, Holt SR, O'Connor PG, Sukumar N, Tetrault JM. Interpreting quantitative urine buprenorphine and norbuprenorphine levels in office-based clinical practice. Drug and alcohol dependence 2017;180:46-51 doi: 10.1016/j.drugalcdep.2017.07.040Gervais JR, Hobbs GA. Use of an Acetyl Derivative to Improve GC-MS Determination of Norbuprenorphine in the Presence of High Concentrations of Buprenorphine in Urine. Journal of Analytical Toxicology 2016;40(3):208-12 doi: 10.1093/jat/bkw001Gorski, T., & Miller, M., Staying Sober: A Guide for Relapse Prevention: Independence Press, 1986Harris, D. S., et al. (2000). "Buprenorphine and naloxone co-administration in opiate-dependent patients stabilized on sublingual buprenorphine." Drug Alcohol Depend 61 (1): 85-94. Hilario, E. Y., et al. (2015). "Denial of urinalysis-confirmed opioid use in prescription opioid dependence." J Subst Abuse Treat 48 (1): 85-90. Hull, M. J., et al. (2008). "Urinary buprenorphine concentrations in patients treated with Suboxone as determined by liquid chromatography-mass spectrometry and CEDIA immunoassay." J Anal Toxicol 32(7): 516-521. Kronstrand R, Nyström I, Andersson M, et al. Urinary Detection Times and Metabolite/Parent Compound Ratios After a Single Dose of Buprenorphine. Journal of Analytical Toxicology 2008;32(8):586-93 doi : 10.1093/ jat /32.8.586. Marin, S. J., et al. (n.d.). "Is it Noroxymorphone or Nornaloxone, and Why Should You Care?". Malbergier, A., et al. (2012). "Monitoring drug use among HIV/AIDS patients in Brazil: should we combine self-report and urinalysis?" Curr HIV Res 10(8): 708-712. Melemis SM. Relapse Prevention and the Five Rules of Recovery. Yale J Biol Med. 2015;88(3):325–332. Published 2015 Sep 3. RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved.

References (continued) Myrick, H., et al. (2002). "Clinical characteristics of under-reporters on urine drug screens in a cocaine treatment study." Am J Addict 11 (4): 255-261.Nasky, K. M., et al. (2009). "False-Positive Urine Screening for Benzodiazepines: An Association with Sertraline?: A Two-year Retrospective Chart Analysis." Psychiatry (Edgmont) 6(7): 36-39.Reisfield, G. M., et al. (2007). "Rational use and interpretation of urine drug testing in chronic opioid therapy." Ann Clin Lab Sci 37(4): 301-314. Schuler, M. S., et al. (2009). "Temporal and gender trends in concordance of urine drug screens and self-reported use in cocaine treatment studies." J Addict Med 3(4): 211-217. Smith ML, Nichols DC, Underwood P, et al. Methamphetamine and amphetamine isomer concentrations in human urine following controlled Vicks VapoInhaler administration. J Anal Toxicol 2014;38(8):524-7 doi: 10.1093/jat/bku077Spierto, F. W., et al. (1997). "Stability of urine creatinine." Clin Chim Acta 264(2): 227-232.Stanciu CN, Gnanasegaram S. Naltrexone and Its Noroxymorphone Minor Metabolite - A Case Report. J Psychoactive Drugs 2019:1-3 doi : 10.1080/02791072.2019.1649507. Suzuki J, Zinser J, Issa M, Rodriguez C. Quantitative testing of buprenorphine and norbuprenorphine to identify urine sample spiking during office-based opioid treatment. Substance abuse 2017;38(4):504-07 doi : 10.1080/08897077.2017.1356796 Tenore PL. Advanced urine toxicology testing. J Addict Dis 2010;29(4):436-48 doi : 10.1080/10550887.2010.509277. Vincent, F., et al. (1999). "Determination of buprenorphine and norbuprenorphine in urine and hair by gas chromatography-mass spectrometry." J Anal Toxicol 23 (4): 270-279. Yonkers, K. A., et al. (2011). "Self-report of illicit substance use versus urine toxicology results from at-risk pregnant women." J Subst Use 16 (5): 372-389. RAMP Copyright 2019, University of Pittsburgh. All Rights Reserved.