Modeling Longitudinal Changes in Buprenorphine Treatment Outcome for Opioid Dependence

Abstract

Introduction: The present analysis describes the longitudinal change in buprenorphine treatment outcome. It also examines several participant characteristics to predict response to buprenorphine.

Methods: Participants (n=501, age>15 years) received buprenorphine/naloxone treatment for 4 weeks, and then were randomly assigned to undergo dose tapering over either 7 days or 28 days. An empirical model was developed to describe the longitudinal changes in treatment outcome. Several patient characteristics were also examined as possible factors influencing treatment outcome.

Results: We have developed a model that captures the general behavior of the longitudinal change in the probability of having an opioid-negative urine sample following buprenorphine treatment. The model captures both the initial increase (i. e., initial response) and the subsequent decrease (i. e., relapse to opioid) in the likelihood of providing an opioid-negative urine sample. Characteristics associated with successful buprenorphine treatment outcome include: having a negative urine test for drugs, having alcohol problems [assessed using alcohol domain of addiction severity index (ASI-alcohol)] at screening, being older, and receiving low cumulative buprenorphine dose. However, ASI-alcohol values were generally low which make the application of the proposed alcohol effect for patients with more severe alcohol problems questionable.

Conclusions: A novel approach for analyzing buprenorphine treatment outcome is presented in this manuscript. This approach describes the longitudinal change in the probability of providing an opioid-free urine sample instead of considering opioid use outcome at a single time point. Additionally, this model successfully describes relapse to opioid. Finally, several patient characteristics are identified as predictors of treatment outcome.

Key words

opioid - detoxification - predictors - opiates - buprenorphine - modeling - longitudinal study

• References

• 1 Beal SL, LB S, Boeckmann AJ. NONMEM Users Guides (1989–2006). Ellicott City, Maryland, USA: Icon Development Solutions; 2006
• 2 Substance Abuse and Mental Health Services Administration . Results from the 2011 National Survey on Drug Use and Health: Summary of National Findings. NSDUH Series H-44, HHS Publication No (SMA) 12-4713. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2012. 1 online resource
• 3 Center for Substance Abuse Treatment . Medication-Assisted Treatment for Opioid Addiction in Opioid Treatment Programs. Pharmacology of Medications Used To Treat Opioid Addiction. Medication-Assisted Treatment for Opioid Addiction in Opioid Treatment Programs. Rockville (MD): 2005
• 4 Walsh SL, Preston KL, Stitzer ML et al. Clinical pharmacology of buprenorphine: ceiling effects at high doses. Clin Pharmacol Therap 1994; 55: 569-580
• 5 Chawarski MC, Schottenfeld RS, O’Connor PG et al. Plasma concentrations of buprenorphine 24 to 72 hours after dosing. Drug Alcohol Depend 1999; 55: 157-163
• 6 Dreifuss JA, Griffin ML, Frost K et al. Patient characteristics associated with buprenorphine/naloxone treatment outcome for prescription opioid dependence: Results from a multisite study. Drug Alcohol Depend
• 7 Ziedonis DM, Amass L, Steinberg M et al. Predictors of outcome for short-term medically supervised opioid withdrawal during a randomized, multicenter trial of buprenorphine-naloxone and clonidine in the NIDA clinical trials network drug and alcohol dependence. Drug Alcohol Depend 2009; 99: 28-36
• 8 Hillhouse M, Canamar CP, Ling W. Predictors of outcome after short-term stabilization with buprenorphine. J Subst Abuse Treatment 2013; 44: 336-342
• 9 Amass L, Bickel WK, Higgins ST et al. A preliminary investigation of outcome following gradual or rapid buprenorphine detoxification. J Addict Dis 1994; 13: 33-45
• 10 Ling W, Hillhouse M, Domier C et al. Buprenorphine tapering schedule and illicit opioid use. Addiction 2009; 104: 256-265
• 11 McLellan AT, Kushner H, Metzger D et al. The Fifth Edition of the Addiction Severity Index. J Subst Abuse Treatment 1992; 9: 199-213
• 12 McGahan P, Griffith J, Parente R et al. Addiction Severity Index: composite scores manual. Philadelphia, PA: Veterans Administration Press; 1986
• 13 Wesson DR, Ling W. The Clinical Opiate Withdrawal Scale (COWS). J Psychoact Drugs 2003; 35: 253-259
• 14 Amass L, Kamien JB, Mikulich SK. Efficacy of daily and alternate-day dosing regimens with the combination buprenorphine-naloxone tablet. Drug Alcohol Depend 2000; 58: 143-152
• 15 Bickel WK, Stitzer ML, Bigelow GE et al. A clinical trial of buprenorphine: comparison with methadone in the detoxification of heroin addicts. Clin Pharmacol Therap 1988; 43: 72-78
• 16 Oreskovich MR, Saxon AJ, Ellis ML et al. A double-blind, double-dummy, randomized, prospective pilot study of the partial mu opiate agonist, buprenorphine, for acute detoxification from heroin. Drug Alcohol Depend 2005; 77: 71-79
• 17 Takama H, Tanaka H, Nakashima D et al. Population pharmacokinetics of intravenous busulfan in patients undergoing hematopoietic stem cell transplantation. Bone Marrow Transpl 2006; 37: 345-351
• 18 Stroup TS, Lieberman JA. Antipsychotic trials in schizophrenia: the CATIE project. Cambridge, UK; New York: Cambridge University Press; 2010
• 19 Lindbom L, Pihlgren P, Jonsson EN. PsN-Toolkit – a collection of computer intensive statistical methods for non-linear mixed effect modeling using NONMEM. Comp Meth Progr Biomed 2005; 79: 241-257
• 20 Lindbom L, Ribbing J, Jonsson EN. Perl-speaks-NONMEM (PsN)–a Perl module for NONMEM related programming. Comp Meth Progr Biomed 2004; 75: 85-94
• 21 Woody GE, Poole SA, Subramaniam G et al. Extended vs. short-term buprenorphine-naloxone for treatment of opioid-addicted youth: a randomized trial. JAMA 2008; 300: 2003-2011
• 22 Hasin D, Liu X, Nunes E et al. Effects of major depression on remission and relapse of substance dependence. Arch Gen Psychiatry 2002; 59: 375-380
• 23 Joe GW, Simpson DD, Sells SB. Treatment process and relapse to opioid use during methadone maintenance. Am J Drug Alcohol Abuse 1994; 20: 173-197
• 24 Dawar A, Queiroz R. Logic, Language, Information and Computation 17^th International Workshop, WoLLIC 2010, Brasilia, Brazil, July 6–9, 2010. Proceedings. Lecture Notes in Computer Science. Berlin, Heidelberg: Springer-Verlag Berlin Heidelberg; 2010
• 25 Marsch LA, Stephens MA, Mudric T et al. Predictors of outcome in LAAM, buprenorphine, and methadone treatment for opioid dependence. Exp Clin Psychopharmacol 2005; 13: 293-302
• 26 Soyka M, Zingg C, Koller G et al. Retention rate and substance use in methadone and buprenorphine maintenance therapy and predictors of outcome: results from a randomized study. Int J Neuropsychopharmacol 2008; 11: 641-653
• 27 Mancino M, Curran G, Han X et al. Predictors of attrition from a national sample of methadone maintenance patients. Am J Drug Alcohol Abuse 2010; 36: 155-160
• 28 Stenbacka M, Beck O, Leifman A et al. Problem drinking in relation to treatment outcome among opiate addicts in methadone maintenance treatment. Drug Alcohol Rev 2007; 26: 55-63
• 29 Joe GW, Simpson DD, Broome KM. Retention and patient engagement models for different treatment modalities in DATOS. Drug Alcohol Depend 1999; 57: 113-125
• 30 Schottenfeld RS, Pakes J, Ziedonis D et al. Buprenorphine – dose-related effects on cocaine and opioid use in cocaine-abusing opioid-dependent humans. Biol Psychiat 1993; 34: 66-74
• 31 Chakrabarti A, Woody GE, Griffin ML et al. Predictors of buprenorphine-naloxone dosing in a 12-week treatment trial for opioid-dependent youth: secondary analyses from a NIDA Clinical Trials Network study. Drug Alcohol Depend 2010; 107: 253-256
• 32 Clark MR, Stoller KB, Brooner RK. Assessment and management of chronic pain in individuals seeking treatment for opioid dependence disorder. Can J Psychiatry/Rev can psychiatrie 2008; 53: 496-508
• 33 Lintzeris N, Bammer G, Rushworth L et al. Buprenorphine dosing regime for inpatient heroin withdrawal: a symptom-triggered dose titration study. Drug Alcohol Depend 2003; 70: 287-294
• 34 Seltman HJ. Experimental Design and Analysis. Pittsburgh, PA: Carnegie Mellon University; 2013
• 35 Charney DA, Palacios-Boix J, Negrete JC et al. Association between concurrent depression and anxiety and six-month outcome of addiction treatment. Psychiatric Serv 2005; 56: 927-933
• 36 Khantzian EJ. The self-medication hypothesis of addictive disorders: focus on heroin and cocaine dependence. American J Psychiatry 1985; 142: 1259-1264
• 37 Brewer DD, Catalano RF, Haggerty K et al. A meta-analysis of predictors of continued drug use during and after treatment for opiate addiction. Addiction 1998; 93: 73-92
• 38 Teesson M, Mills K, Ross J et al. The impact of treatment on 3 years’ outcome for heroin dependence: findings from the Australian Treatment Outcome Study (ATOS). Addiction 2008; 103: 80-88
• 39 Dreifuss JA, Griffin ML, Frost K et al. Patient characteristics associated with buprenorphine/naloxone treatment outcome for prescription opioid dependence: Results from a multisite study. Drug Alcohol Depend 2013; 131: 112-118
• 40 Fatseas M, Denis C, Lavie E et al. Relationship between anxiety disorders and opiate dependence – a systematic review of the literature: implications for diagnosis and treatment. J Subst Abuse Treatment 2010; 38: 220-230
• 41 Benningfield MM, Dietrich MS, Jones HE et al. Opioid dependence during pregnancy: relationships of anxiety and depression symptoms to treatment outcomes. Addiction 2012; 107 (Suppl. 01) 74-82
• 42 Warden D, Subramaniam GA, Carmody T et al. Predictors of attrition with buprenorphine/naloxone treatment in opioid dependent youth. Addict Behav 2012; 37: 1046-1053