Original Research January 14, 2026

Identifying Optimal Thresholds for Early Opioid Use Frequency in Predicting Buprenorphine Outcomes

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J Clin Psychiatry 2026;87(1):25m16042

Abstract

Objective: Early prognostic indicators of nonresponse to buprenorphine treatment for opioid use disorder can inform targeted efforts to improve outcomes. Opioid use in the first 2–3 weeks of treatment predicts later outcomes, yet it is unclear what frequency of opioid use confers risk. We aimed to (1) identify thresholds for the frequency of early opioid use that optimally predict later sustained use and (2) quantify associations between thresholds and continuous treatment outcomes.

Method: We used data from 2 clinical trials of buprenorphine (N=562; mean age=34 years; 38% female), which were conducted from 2006-2009 and 2007-2011. Area under the receiver operating characteristic curve analyses identified optimal thresholds for opioid frequency during the first 4 weeks in predicting sustained use during weeks 5–12 (ie, 4 consecutive weeks with an opioid-positive or missing urine drug screen). Negative binomial regressions examined associations between early nonresponse and opioid-free and retention weeks.

Results: Sustained opioid use was optimally predicted by ≥1 day of opioid use in the first 2 weeks (sensitivity=0.747; specificity=0.688; positive predictive value [PPV]=0.524; negative predictive value [NPV]=0.856) and ≥2 days of use in the first 3 weeks (sensitivity=0.649; specificity=0.810; PPV=0.611; NPV=0.834). Both thresholds were negatively associated with opioid-free and retention weeks.

Conclusions: Even very low levels of opioid use in the first 2–3 weeks of buprenorphine treatment signal risk for poor outcomes. Emphasizing abstinence or near abstinence early in treatment might help promote long-term stability. Identified thresholds can be used to identify patients who may benefit from treatment adjustments and close monitoring.

J Clin Psychiatry 2026;87(1):25m16042

Author affiliations are listed at the end of this article.

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  1. Connery HS. Medication-assisted treatment of opioid use disorder: review of the evidence and future directions. Harv Rev Psychiatry. 2015;23(2):63–75. PubMed CrossRef
  2. Weiss RD, Potter JS, Fiellin DA, et al. Adjunctive counseling during brief and extended buprenorphine-naloxone treatment for prescription opioid dependence: a 2-phase randomized controlled trial. Arch Gen Psychiatry. 2011;68(12):1238–1246. PubMed CrossRef
  3. Lee JD, Nunes EV, Novo P, et al. Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial. Lancet. 2018;391(10118):309–318. PubMed CrossRef
  4. McDermott KA, Griffin ML, Connery HS, et al. Initial response as a predictor of 12-week buprenorphine-naloxone treatment response in a prescription opioid dependent population. J Clin Psychiatry. 2015;76(2):189–194. PubMed CrossRef
  5. Luo SX, Feaster DJ, Liu Y, et al. Individual-level risk prediction of return to use during opioid use disorder treatment. JAMA Psychiatry. 2024;81(1):45–56. PubMed CrossRef
  6. McHugh RK, Bailey AJ, Weiss RD, et al. Protocol for harmonization of randomized trials testing the addition of behavioral therapy to buprenorphine for opioid use disorder. Drug Alcohol Depend Rep. 2024;11:100226. PubMed CrossRef
  7. Ling W, Hillhouse M, Ang A, et al. Comparison of behavioral treatment conditions in buprenorphine maintenance. Addiction. 2013;108(10):1788–1798. PubMed CrossRef
  8. McHugh RK, Bailey AJ, McConaghy BA, et al. Behavioral therapy as an adjunct to buprenorphine treatment for opioid use disorder: a secondary analysis of 4 randomized clinical trials. JAMA Netw Open. 2025;8(8):e2528529. PubMed CrossRef
  9. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. American Psychiatric Publishing, Inc; 1994.
  10. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. American Psychiatric Publishing, Inc; 2000.
  11. Zhang Z. Multiple imputation with multivariate imputation by chained equation (MICE) package. Ann Transl Med. 2016;4(2):30. PubMed CrossRef
  12. Unal I. Defining an optimal cut-point value in ROC analysis: an alternative approach. Comput Math Methods Med. 2017;2017:3762651. PubMed CrossRef
  13. Le Grange D, Accurso EC, Lock J, et al. Early weight gain predicts outcome in two treatments for adolescent anorexia nervosa: early weight gain for adolescent anorexia nervosa. Int J Eat Disord. 2014;47(2):124–129. PubMed CrossRef
  14. Brensilver M, Heinzerling KG, Swanson AN, et al. A retrospective analysis of two randomized trials of bupropion for methamphetamine dependence: suggested guidelines for treatment discontinuation/augmentation. Drug Alcohol Depend. 2012;125(1-2):169–172. PubMed CrossRef
  15. Robin X, Turck N, Hainard A, et al. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinforma. 2011;12(1):77. PubMed CrossRef
  16. Thiele C, Hirschfeld G. Cutpointr: improved estimation and validation of optimal cutpoints in R. J Stat Software. 2021;98:1–27. CrossRef
  17. Venables W, Ripley B. Modern Applied Statistics with S. Fourth Edition. Accessed October 24, 2024. https://www.stats.ox.ac.uk/pub/MASS4/.
  18. Theisen J, Weinstein ZM, Davoust M, et al. Patient and provider perspectives on the elimination of urine drug testing in office-based addiction treatment. Subst Use Addctn J. 2025:29767342251360850.
  19. Larimer ME, Palmer RS, Marlatt GA. Relapse prevention: an overview of Marlatt’s cognitive-behavioral model. In: Psychosocial Treatments. Routledge; 2004.
  20. Grande LA, Cundiff D, Greenwald MK, et al. Evidence on buprenorphine dose limits: a review. J Addict Med. 2023;17(5):509–516. PubMed CrossRef
  21. Taylor JL, Johnson S, Cruz R, et al. Integrating harm reduction into outpatient opioid use disorder treatment settings: harm reduction in outpatient addiction treatment. J Gen Intern Med. 2021;36(12):3810–3819. PubMed CrossRef
  22. Chan B, Gean E, Arkhipova-Jenkins I, et al. Retention strategies for medications for opioid use disorder in adults: a rapid evidence review. J Addict Med. 2021;15(1):74–84. PubMed CrossRef
  23. 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(1-2):112–118. PubMed CrossRef
  24. Volkow ND. The epidemic of fentanyl misuse and overdoses: challenges and strategies. World Psychiatry. 2021;20(2):195–196. PubMed CrossRef
  25. Connery HS, Weiss RD. Discontinuing buprenorphine treatment of opioid use disorder: what do we (not) know?. Am J Psychiatry. 2020;177(2):104–106. PubMed CrossRef
  26. Perski O, Hébert ET, Naughton F, et al. Technology-mediated just-in-time adaptive interventions (JITAIs) to reduce harmful substance use: a systematic review. Addiction. 2022;117(5):1220–1241. PubMed CrossRef