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Prescription amphetamines in people with opioid use disorder and co-occurring psychostimulant use disorder initiating buprenorphine: an analysis of treatment retention and overdose risk
  1. Vitor Tardelli1,2,
  2. Kevin Y Xu3,
  3. Adam Bisaga4,5,
  4. Frances R Levin4,
  5. Thiago M Fidalgo1,
  6. Richard A Grucza6,7
  1. 1 Department of Psychiatry, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
  2. 2 Translational Addictions Research Lab, Centre for Addiction and Mental Health, Department of Psychiatr, University of Toronto, Toronto, Ontario, Canada
  3. 3 Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA
  4. 4 Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York City, New York, USA
  5. 5 Division of Substance Use Disorders, New York State Psychiatric Institute, New York City, New York, USA
  6. 6 Department of Family and Community Medicine, Saint Louis University, St. Louis, Missouri, USA
  7. 7 Department of Health and Outcomes Research, Saint Louis University, St. Louis, Missouri, USA
  1. Correspondence to Dr Vitor Tardelli, Department of Psychiatry, Universidade Federal de Sao Paulo, Sao Paulo, Brazil; vitorstardelli{at}


Background Attention-deficit and hyperactivity disorder (ADHD) is frequently diagnosed in patients with substance use disorders (SUDs), including opioids. There remains concern about the safety and efficacy of prescription amphetamines (PAs) and their impact on effectiveness of opioid use disorder (OUD) treatment with buprenorphine.

Objectives To assess the effect of PAs on OUD buprenorphine treatment retention and/or SUD-related emergency admission or drug-related poisonings.

Methods We used a retrospective cohort design with a secondary analysis of data from Merative MarketScan Commercial and Multi-State Medicaid Databases from 1 January 2006 to 31 December 2016. Individuals included were aged 12–64 years, had an OUD diagnosis and were prescribed buprenorphine. Our analysis used multivariable Cox regression to evaluate the relationship between PA receipt and time to buprenorphine discontinuation. The second part focused on subsamples of buprenorphine initiators who had either (1) any SUD-related emergency admissions or (2) drug-related poisoning. These outcomes were modelled as a function of PA exposure using conditional logistic regression models as part of a within-person, case-crossover design.

Findings Our sample had 90 269 patients with OUD (mean age 34.2 years (SD=11.3)) who initiated buprenorphine. Being prescribed a PA was associated with improved buprenorphine retention among individuals both with (adjusted HR (aHR) 0.91 (95% CI 0.86 to 0.97)) and without a concurrent psychostimulant use disorder (PSUD) (aHR 0.92 (95% CI 0.90 to 0.93)).

Conclusions PA use was associated with improved buprenorphine retention in people with OUD with and without co-occurring PSUD. The risks of acute SUD-related events and drug-related poisonings associated with PA use did not differ when comparing PA-using days with days without PA use.

Clinical implications Patients with OUD on buprenorphine should receive treatment with a PA when indicated.

  • substance misuse
  • adult psychiatry

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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  • TMF and RAG are joint senior authors.

  • VT and KYX are joint first authors.

  • Twitter @vitorstardelli

  • Contributors Concept: VT, KYX, TMF, RAG, FRL. Design: VT, KYX, TMF, RAG. Analysis of data: KYX. Interpretation of data: VT, KYX, TMF, RAG, AB, FRL. Drafting of manuscript: VT, KYX, TMF. Obtained funding: RAG. Administrative, technical or material support: RAG. Critical revision for important intellectual content: VT, KYX, TMF, RAG, AB, FRL. KYX is guarantor.

  • Funding This project was funded by R21 DA044744 (PI: RAG/Laura Bierut). Effort for some personnel was supported by grants T32 DA015035 (KYX, PI: Kathleen Bucholz, Jeremy Goldbach), K12 DA041449 (KYX, PI: Laura Bierut, Patricia Cavazos-Rehg), and by a fellowship from the Saint Louis University Research Institute (RAG) but these grants did not fund the analyses of the Merative MarketScan Multi-State Medicaid Database data performed by KYX. CADR is supported in part by the Washington University Institute of Clinical and Translational Sciences via grants UL1 TR002345 (from the National Centre for Advancing Translational Sciences of the National Institutes of Health).

  • Competing interests AB received grants from National Institutes of Health (NIH), research support and medication samples from Alkermes, and consulting fees from OpheliaHealth, a telehealth provider for opioid use disorder. FRL reported consulting for Major League Baseball, receiving grants from the National Institutes of Health (NIH) and Substance Abuse and Mental Health Services Administration (SAMHSA), receiving a salary from the New York State Psychiatric Institute, and receiving non-financial support from US World Meds, Alkermes and Indivior outside the submitted work and serving as an uncompensated member of scientific advisory boards of Alkermes, Indivior, Novartis International, Teva Pharmaceutical Industries and US WorldMeds. RAG reported receiving grants from the NIH and Arnold Ventures during the conduct of the study, consulting for Janssen Pharmaceuticals and receiving personal fees for grant reviews from the NIH outside the submitted work.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.