Impact of Depressive Symptom Severity on Buprenorphine/Naloxone and Methadone Outcomes in People With Prescription-Type Opioid Use Disorder: Results From a Pragmatic Randomized Controlled Trial

Abstract

Objective

To evaluate the impact of depressive symptom severity on opioid use and treatment retention in individuals with prescription-type opioid use disorder (POUD).

Method

We analyzed data from a multi-centric, pragmatic, open-label, randomized controlled trial comparing buprenorphine/naloxone to methadone models of care in 272 individuals with POUD. Opioid use was self-reported every two weeks for 24 weeks using the Timeline Followback. Depressive symptom severity was self-reported with the Beck Depression Inventory at baseline, week 12 and week 24.

Results

Baseline depressive symptom severity was not associated with opioid use nor treatment retention. At week 12, moderate depressive symptoms were associated with greater opioid use while mild to severe depressive symptoms were associated with lowered treatment retention. At week 24, moderate depressive symptoms were associated with greater opioid use.

Conclusions

Ongoing depressive symptoms lead to poorer outcomes in POUD. Clinicians are encouraged to use integrative approaches to optimize treatment outcomes. This study was registered in ClinicalTrials.gov (NCT03033732) on January 27^th, 2017, prior to participants enrollment.

Keywords:

• Analgesics; opioid; buprenorphine; naloxone drug combination; methadone; opioid-related disorders; depressive disorder; major; humans; randomized controlled trial

Acknowledgments

GB received scholarships from the Institut universitaire sur les dépendances, the Quebec Network on Suicide, Mood Disorders and Related Disorders, and the Centre hospitalier de l’Université de Montréal Research Centre. AA received funding from the Université de Montréal Faculty of Medicine. CM received funding from the Institut universitaire sur les dépendances, the Gaulin Foundation and the Centre hospitalier de l’Université de Montréal Research Centre. MES is supported by a Michael Smith Foundation for Health Research and St. Paul’s Foundation Scholar Award. BLF is supported by a clinician scientist award from the Department of Family and Community Medicine and by the Addiction Psychiatry Chair of the Department of Psychiatry, University of Toronto. BLF receives or has received support from Pfizer Global Research Awards in Nicotine Dependence (GRAND) Program, Brainsway, Bioprojet, Alkermes, Canopy, ACS, and non-financial support from Aurora for work outside this study. AB holds a Canadian Institutes of Health Research Fellowship, Calgary Health Trust, Alberta Innovates Graduate Scholarship and Harley N. Hotchkiss Graduate Scholarship. DJA holds a research scholar award from the Fonds de Recherche du Québec en Santé.

Disclosure statement

Dr. Laurent Elkrief is a shareholder and employee of Strem biotechnologies and OneCare. Dr. M. Eugenia Socias has received partial support from Indivior’s Investigator Initiated Study programme for work outside this study. Dr. Bernard Le Foll receives or has received support from Pfizer Global Research Awards in Nicotine Dependence (GRAND) Program, Brainsway, Bioprojet, Alkermes, Canopy, ACS, and non-financial support from Aurora for work outside this study. Dr. Stephanie Marsan was a member of an advisory committee for Indivior until November 2021. Dr. Didier Jutras-Aswad will also receive investigational products (2022-24) from Cardiol Therapeutics and Exka for clinical trials funded by Quebec Ministry of Health and Social Services. Gabriel Bastien, Anita Abboud, Christina McAnulty, Omar Ledjiar, Dr. Anees Bahji, and Dr. Suzanne Brissette report no financial relationships with commercial interests.

Data availability statement

Following publication, individual deidentified participant data and a data dictionary can be made available upon reasonable request from JF at [email protected], following approval of a proposal and a signed data access agreement. Please also contact this person for the study protocol or statistical analysis plan.

Additional information

Funding

This work was supported by the Canadian Institutes of Health Research (CIHR) through the Canadian Research Initiative in Substance Misuse [CRISM; Grant Numbers CIS144301, CIS-144302, CIS-144303, CIS-144304; REN-477 907; REN-181 678; REN-181 677; REN-181 673; REN-477 708]. CRISM received independent funding through a CIHR priority-driven initiative [Grant Numbers SMN139148, SMN-139149, SMN-139150, SMN-139151]. Knowledge transfer activities were funded by Health Canada. None of the funders had any role in study design, data collection, analysis, interpretation, or writing of the report.