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Randomized Controlled Trial
. 2023 Aug;68(8):572-585.
doi: 10.1177/07067437221145013. Epub 2022 Dec 14.

Effects of Buprenorphine/Naloxone and Methadone on Depressive Symptoms in People with Prescription Opioid Use Disorder: A Pragmatic Randomised Controlled Trial

Gabriel Bastien  1   2 , Christina McAnulty  1   2 , Omar Ledjiar  3 , M Eugenia Socias  4   5 , Bernard Le Foll  6   7   8   9   10   11 , Ron Lim  12 , Ahmed N Hassan  6   7   9 , Suzanne Brissette  2   13 , Stéphanie Marsan  2   13 , Annie Talbot  2   13 , Didier Jutras-Aswad  1   2 ; OPTIMA Research Group within the Canadian Research Initiative in Substance Misuse
Affiliations
Randomized Controlled Trial

Effects of Buprenorphine/Naloxone and Methadone on Depressive Symptoms in People with Prescription Opioid Use Disorder: A Pragmatic Randomised Controlled Trial

Gabriel Bastien et al. Can J Psychiatry. 2023 Aug.

Abstract
in English, French

Objective: This study aimed to evaluate the effectiveness of flexible take-home dosing of buprenorphine/naloxone (BUP/NX) and methadone standard model of care in reducing depressive symptoms in people with prescription-type opioid use disorder (POUD). This trial also evaluated whether improvements in depressive symptoms were mediated by opioid use.

Methods: Analyzed data came from the OPTIMA study (clinicaltrials.gov identifier: NCT03033732), a pragmatic randomised controlled trial comparing flexible take-home dosing of BUP/NX and methadone standard model of care for reducing opioid use in people with POUD. A total of 272 participants were recruited in four Canadian provinces. Participants were randomised 1:1 to BUP/NX or methadone. After treatment induction, past two-week opioid use was measured using the Timeline Followback every two weeks for a total of 24 weeks. Depressive symptoms were measured with the Beck Depression Inventory at baseline, weeks 12 and 24.

Results: Both BUP/NX and methadone significantly reduced depressive symptoms at week 12 (aβ ± SE = -3.167 ± 1.233; P < 0.001) and week 24 (aβ ± SE = -7.280 ± 1.285; P < 0.001), with no interaction between type of treatment and time (P = 0.284). Improvements in depressive symptoms were only partially mediated by a reduction in opioid use (proportion mediated = 36.8%; 95% confidence interval = -1.158 to -0.070; P = 0.015).

Conclusions: BUP/NX and methadone showed similar effectiveness in decreasing comorbid depressive symptoms in people with POUD. This effect was partially explained by a reduction in opioid use. As both treatments seem equally effective, clinicians are encouraged to tailor the selection of OAT to patients' needs and characteristics.

Objectif: La présente étude visait à évaluer l’efficacité d'une approche flexible de doses à emporter à domicile de buprénorphine/naloxone (BUP/NX) et du modèle de soins standard avec la méthadone pour réduire les symptômes dépressifs chez les personnes vivant avec un trouble lié à l’utilisation d’opioïdes de prescription (TUOP). Le présent essai a également évalué si les améliorations des symptômes dépressifs étaient médiées par l’utilisation d’opioïdes.

Méthodes: Les données analysées provenaient de l’étude OPTIMA (identifiant clinicaltrials.gov : NCT03033732), un essai randomisé contrôlé pragmatique comparant l'usage flexible de dosesà emporter à domicile de BUP/NX et le modèle de soins standard avec la méthadone pour réduire la consommation d’opioïdes chez les personnes ayant un TUOP. Un total de 272 participants a été recruté dans quatre provinces canadiennes. Les participants ont été randomisés 1:1 à lau BUP/NX ou à la méthadone. Après l'induction du traitement, l’utilisation d’opioïdes dans les deux dernières semaines a été mesurée à l’aide du Timeline Followback à toutes les deux semaines pendant 24 semaines. Les symptômes dépressifs étaient mesurés à l’aide de l’Inventaire de dépression de Beck au début de l'étude et aux semaines 12 et 24.

Résultats: La BUP/NX et la méthadone réduisaient significativement toutes deux les symptômes dépressifs à la 12e semaine (aβ ± SE = -3,167 ± 1,233; p,<,0,001) et à la 24e semaine (aβ ± SE = -7,280 ± 1,285; p < 0,001), sans interaction entre le type de traitement et le temps (p = 0,284). Les améliorations des symptômes dépressifs n’étaient que partiellement médiées par une réduction de l’utilisation d’opioïdes (proportion médiée= 36,8%; IC à 95% 1,158 à −0,070; p = 0,015).

Conclusions: La BUP/NX et la méthadone ont démontré une efficacité semblable à réduire les symptômes dépressifs comorbides chez des personnes ayant un TUOP. Cet effet s’expliquait partiellement par une réduction de l’utilisation d’opioïdes. Comme les deux traitements semblent similairement efficaces, les cliniciens sont encouragés d’adapter la sélection du traitement agoniste opioïde aux besoins et aux caractéristiques des patients.

Keywords: comorbidity; depressive disorders; dual diagnosis; major depressive disorder; randomised controlled trial; substance use disorders.

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Conflict of interest statement

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
CONSORT flow diagram illustrating pre-screening, screening, randomising, and analysis with the number of participants for each step. *Thirteen participants were screened twice but are counted only once in the flowchart. **Other reasons for exclusions were unspecified (n = 14), incomplete screening (n = 4), failure to complete baseline visit within a 28-day time window (n = 3), and incarceration (n = 1). ***One participant attempted suicide and withdrew consent six days later. BDI-II, Beck Depression Inventory – Second Edition; BUP/NX, buprenorphine/naloxone; COVID-19, coronavirus disease 2019; n, number of participants; OAT, opioid agonist treatment; POUD, prescription opioid use disorder; SAE, serious adverse events.
Figure 2.
Figure 2.
Mean (±SD) depressive symptoms scores across study visits for methadone and buprenorphine/naloxone treatment groups. Baseline depressive scores were similar between treatment groups. Depressive symptoms showed a constant decrease throughout the study period. BDI-II, Beck Depression Inventory – Second Edition.
Figure 3.
Figure 3.
Results from the mediation analyses using imputed data. (A) Being on opioid agonist treatment from baseline to week 12 significantly reduced days of opioid use (P < 0.001) and depressive symptoms (P < 0.001) at week 12. Days of opioid use in the past two weeks predicted depressive symptoms at week 12 (P = 0.003). The direct path (P = 0.001) and total effect (P < 0.001) were significant. The mediated effect was not significant (P = 0.281). (B) Being on opioid agonist treatment from baseline to week 24 significantly reduced days of opioid use (P < 0.001) and depressive symptoms (P < 0.001) at week 24. The combined effect of time on OAT and days of opioid use in the past two weeks significantly decreased depressive symptoms at week 24 (P < 0.001). The direct effect (P < 0.001), and the total effect (P < 0.001) were significant, while the mediated effect was not (P = 0.140). (C) Being on opioid agonist treatment from week 12 to week 24 significantly decreased depressive symptoms at week 24 (P = 0.002) but increased days of opioid use at week 24 (P = 0.002). The indirect (P = 0.014), direct (P < 0.001) and total (P = 0.001) effects were all significant.
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