Impact of opioid agonist treatment on mental health in patients with opioid use disorder: a systematic review and network meta-analysis of randomized clinical trials

ABSTRACT

Background: There is a knowledge gap in systematic reviews on the impact of opioid agonist treatments on mental health.

Objectives: We compared mental health outcomes between different opioid agonist treatments and placebo/waitlist, and between the different opioids themselves.

Methods: This meta-analysis of randomized clinical trials (RCTs) was pre-registered at PROSPERO (CRD42018109375). Embase, MEDLINE, PsychInfo, CINAHL Complete, and Web of Science Core Collection were searched from inception to May 2020. RCTs were included if they compared opioid agonists with each other or with placebo/waitlist in the treatment of patients with opioid use disorder and reported at least one mental health outcome after 1-month post-baseline. Studies with psychiatric care, adjunct psychotropic medications, or unbalanced psychosocial services were excluded. The primary outcome was overall mental health symptomatology, e.g. Symptom Checklist 90 total score, between opioids and placebo/waitlist. Random effects models were used for all the meta-analyses.

Results: Nineteen studies were included in the narrative synthesis and 15 in the quantitative synthesis. Hydromorphone, diacetylmorphine (DAM), methadone, slow-release oral morphine, buprenorphine, and placebo/waitlist were among the included interventions. Based on the network meta-analysis for primary outcomes, buprenorphine (SMD (CI95%) = −0.61 (−1.20, −0.11)), DAM (−1.40 (−2.70, −0.23)), and methadone (−1.20 (−2.30, −0.11)) were superior to waitlist/placebo on overall mental health. Further direct pairwise meta-analysis indicated that overall mental health improved more in DAM compared to methadone (−0.23 (−0.34, −0.13)).

Conclusions: Opioid agonist treatments used for the treatment of opioid use disorder improve mental health independent of psychosocial services.

KEYWORDS:

• Opioid
• buprenorphine
• methadone
• mental health
• depression

Author contributions

EMZ had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. EMZ contributed to the conceptualization, designed the study, coordinated the study, carried out the statistical analyses, provided the first draft, and acted as co-senior reviewer in cases of disagreement. KZ, KY, MM, and JW carried out screening, data extraction, and quality assessment. They also revised the manuscript for important intellectual content. AM contributed to the design, provided methodological guidance, and revised the manuscript for important intellectual content. PB and UV provided essential data for some of the studies included in this review. PB, UV, CS, KJ, SA, and MK provided consultation during the study, contributed to the interpretation of results and revised the manuscript for important intellectual content. MK conceptualized the study, contributed to the design, helped with coordination of the study, and acted as cosenior reviewer in cases of disagreement.

Data availability

All data supporting the findings of this study are available from the corresponding author, EMZ, upon reasonable request.

Disclosure of interest

EMZ, KZ, KY, MM, JW, AM, KJ, CS, SA, and RMK declare no competing interests. PB received grants from The Dutch Ministry of Health, Welfare and Sports (VWS), during the conduct of the study. UV received speaker’s honoraria from Mundipharma GmbH and traveling expenses from Camurus GmbH and Mundipharma GmbH.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website.

Additional information

Funding

This research received no specific grant from any funding agency, commercial or not-for-profit sectors.