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.
