AbstractBackgroundNon-adherence to medication is a major obstacle in the treatment of depressive disorders. We systematically reviewed the literature to evaluate the effectiveness of interventions aimed at improving adherence to medication among adults with depressive disorders with emphasis on initiation and implementation phase.MethodsWe searched Medline, EMBASE, The Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO, Social Science Citation Index and Science Citation Index for randomized or non-randomized controlled trials up to January 2022. Risk of bias was assessed using the criteria of the Cochrane Collaboration. Meta-analyses, cumulative and meta-regression analyses for adherence were conducted.ResultsForty-six trials (n = 24,324) were included. Pooled estimate indicates an increase in the probability of adherence to antidepressants at 6 months with the different types of interventions (OR 1.33; 95% CI: 1.09 to 1.62). The improvement in adherence is obtained from 3 months (OR 1.62, 95% CI: 1.25 to 2.10) but it is attenuated at 12 months (OR 1.25, 95% CI: 1.02 to 1.53). Selected articles show methodological differences, mainly the diversity of both the severity of the depressive disorder and intervention procedures. In the samples of these studies, patients with depression and anxiety seem to benefit most from intervention (OR 2.77, 95% CI: 1.74 to 4.42) and collaborative care is the most effective intervention to improve adherence (OR 1.88, 95% CI: 1.40 to 2.54).ConclusionsOur findings indicate that interventions aimed at improving adherence to medication among adults with depressive disorders are effective up to six months. However, the evidence on the effectiveness of long-term adherence is insufficient and supports the need for further research efforts.Trial registrationInternational Prospective Register for Systematic Reviews (PROSPERO) number:CRD42017065723.