Discontinuation of antidepressants after remission with antidepressant medication in major depressive disorder: a systematic review and meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 32704061 · doi:10.1038/s41380-020-0843-0
What was done
A systematic review and random-effects meta-analysis evaluating the risk of depressive relapse and treatment failure in major depressive disorder (MDD) patients who achieved remission. The meta-analysis compared continuing the remission-achieving antidepressant versus switching to placebo across 40 studies (n = 8,890), evaluating subgroups by drug class, dosing regimen, treatment duration, and age group.
What was found
Continued antidepressant therapy significantly reduced relapse compared to placebo discontinuation (20.9% vs. 39.7%; OR = 0.38, 95% CI: 0.33–0.43, p < 0.00001). Relapse rate differences by class were 25.3% for tricyclics (OR = 0.30, 95% CI: 0.17–0.50), 21.8% for SSRIs (OR = 0.33, 95% CI: 0.28–0.38), and 16.0% for other newer agents (OR = 0.44, 95% CI: 0.36–0.54). Flexible dosing showed a larger relative reduction (OR = 0.30) than fixed dosing (OR = 0.41). Protection remained consistent at 6 months (19.6% vs. 37.6%; OR = 0.41) and past 1 year (19.9% vs. 39.8%; OR = 0.35). All-cause dropout was lower with antidepressants than placebo (43% vs. 58%; OR = 0.47), while tolerability discontinuation was ~4% in both groups. In adolescents, overall relapse rates were higher (41.0% vs. 66.7%; OR = 0.32).
Why it matters
This review provides strong evidence supporting antidepressant maintenance therapy for at least 6 to 12 months after remission to prevent depressive relapse, highlighting SSRIs and flexible dosing as effective strategies.
Limits
The abstract does not distinguish between acute antidepressant withdrawal effects and genuine depressive relapse following placebo substitution. Long-term outcomes beyond one year and specific tapering schedules are not detailed.
Cited by
- contradicts Long-term use of SSRIs and SNRIs for depression is only slightly better in terms of outcomes compared to placebo.