Efficacy and tolerability of antidepressants in the treatment of adolescents and young adults with depression and substance use disorders: a systematic review and meta-analysis

Aims: To measure the effectiveness of antidepressants for adolescents and young adults with co-occurring depression and substance use disorder.

Design, setting and participants: Meta-analysis of randomized controlled clinical trials. A comprehensive literature search of PubMed, Cochrane, Embase, Web of Science and PsychINFO was conducted (from 1970 to 2013). Prospective, parallel groups, double-blind, controlled trials with random assignment to an antidepressant or placebo on young patients (age ≤ 25 years) who met diagnostic criteria of both substance use and unipolar depressive disorder were included. Five trials were selected for this analysis and included 290 patients.

Measurements: Our efficacy outcome measures were depression outcomes (dichotomous and continuous measures) and substance-use outcomes (change of frequency or quantity of substance-use). Secondary analysis was conducted to access the tolerability of antidepressant treatment.

Findings: For dichotomous depression outcome, antidepressants group was significantly more effective than placebo group [risk ratio (RR) = 1.21; 95% confidence interval (CI) 1.01-1.45], with low heterogeneity (I(2) = 0%). Although no statistically significant effects for continuous depression outcome [standardized mean differences (SMD) = -0.13; 95% CI, -0.55 to 0.30] were found with moderate heterogeneity (I(2) = 63%), subgroup analysis showed that the medicine group with a sample size of more than 50 showed statistically significant efficacy compared with the placebo group (SMD -0.53, 95% CI -0.82 to -0.25). Moreover, there was no significant difference for substance-use outcomes and tolerability outcomes between the medication and placebo groups.

Conclusions: Antidepressant medication has a small overall effect in reducing depression in young patients with combined depressive and substance-use disorders, but does not appear to improve substance use outcomes.