When to stop medication in unipolar depression: A systematic review and a meta-analysis of randomized controlled trials.

Background: Currently, there is no clear answer to the question of how long antidepressants should be continued or when they can be safely discontinued.

Methods: Pubmed/Medline was systematically searched from inception to Feb 20, 2021. Double-blind, randomized placebo-controlled trials (RCTs) with maintenance phase were selected to examine the relationship between relapse rate and treatment duration. Among 5351 screened records, 37 RCTs meeting inclusion criteria were selected. Odds ratios were calculated from relapse rates for each study and pooled in random-effect models. Possible predictors of effect sizes, i.e., open-label treatment duration, double-blind phase duration, age, medication type, history of recurrence, were analyzed by meta-regression.

Results: The random-effects model showed the superiority of active medication over placebo for relapse during the follow-up phase (OR = 0.37; 95 % CI, 0.32-0.42). The meta-regression did not show a relationship between treatment duration and the effect sizes. Other clinical variables were not related with effect sizes. Subgroup analysis revealed that, for atypical ADs the effect size increased as the treatment duration increased. Further analysis showed that the relapse rate in the placebo group decreased as function of time, which reduced the absolute benefit of continued treatment.

Conclusion: The results may indicate that long term use of antidepressants may not be justified, and this strategy may expose the patients to more adverse effects.