Discontinuation of antidepressants after remission with antidepressant medication in major depressive disorder: a systematic review and meta-analysis

Abstract

A significant clinical issue encountered after a successful acute major depressive disorder (MDD) treatment is the relapse of depressive symptoms. Although continuing maintenance therapy with antidepressants is generally recommended, there is no established protocol on whether or not it is necessary to prescribe the antidepressant used to achieve remission. In this meta-analysis, the risk of relapse and treatment failure when either continuing with the same drug used to achieved remission or switching to a placebo was assessed in several clinically significant subgroups. The pooled odds ratio (OR) (±95% confidence intervals (CI)) was calculated using a random effects model. Across 40 studies ( n = 8890), the relapse rate was significantly lower in the antidepressant group than the placebo group by about 20% (OR = 0.38, CI: 0.33–0.43, p < 0.00001; 20.9% vs 39.7%). The difference in the relapse rate between the antidepressant and placebo groups was greater for tricyclics (25.3%; OR = 0.30, CI: 0.17–0.50, p < 0.00001), SSRIs (21.8%; OR = 0.33, CI: 0.28–0.38, p < 0.00001), and other newer agents (16.0%; OR = 0.44, CI: 0.36–0.54, p < 0.00001) in that order, while the effect size of acceptability was greater for SSRIs than for other antidepressants. A flexible dose schedule (OR = 0.30, CI: 0.23–0.48, p < 0.00001) had a greater effect size than a fixed dose (OR = 0.41, CI: 0.36–0.48, p < 0.00001) in comparison to placebo. Even in studies assigned after continuous treatment for more than 6 months after remission, the continued use of antidepressants had a lower relapse rate than the use of a placebo (OR = 0.40, CI: 0.29–0.55, p < 0.00001; 20.2% vs 37.2%). The difference in relapse rate was similar from a maintenance period of 6 months (OR = 0.41, CI: 0.35–0.48, p < 0.00001; 19.6% vs 37.6%) to over 1 year (OR = 0.35, CI: 0.29–0.41, p < 0.00001; 19.9% vs 39.8%). The all-cause dropout of antidepressant and placebo groups was 43% and 58%, respectively, (OR = 0.47, CI: 0.40–0.55, p < 0.00001). The tolerability rate was ~4% for both groups. The rate of relapse (OR = 0.32, CI: 0.18–0.64, p = 0.0010, 41.0% vs 66.7%) and all-cause dropout among adolescents was higher than in adults. To prevent relapse and treatment failure, maintenance therapy, and careful attention for at least 6 months after remission is recommended. SSRIs are well-balanced agents, and flexible dose adjustments are more effective for relapse prevention.

Efficacy and acceptability of pharmacological, psychosocial, and brain stimulation interventions in children and adolescents with mental disorders: an umbrella review

“…We ultimately included 14 NMAs and 90 MAs, reporting on 15 disorders or groups of disorders. For ADHD, we included three NMAs 5,20,21 and 21 MAs 22‐42 ; for autism, one NMA 43 and 21 MAs 12,44‐63 (including one focusing on comorbid anxiety disorders and autism) 12 ; for depressive disorders, two NMA 7,10 and seven MAs 64‐70 ; for obsessive‐compulsive disorder, one NMA 71 and six MAs 72‐77 ; for anxiety disorders, two NMAs 11,78 and five MAs 12,79‐82 (plus two MAs specific on social anxiety disorder 83,84 ); for enuresis, one NMA 85 and six MAs 86‐91 , for disruptive behavior/dissocial/conduct disorders, five MAs 92‐96 (plus one focusing on youth with comorbid ADHD) 25 ; for eating disorders, one NMA 97 and four MAs 98‐101 ; for schizophrenia spectrum disorders, three NMAs 8,102,103 and two MAs 104,105 ; for bipolar disorder, four MAs 106‐109 ; for tic disorder, two MAs 110,111 ; for Tourette's disorder, two MAs 112,113 ; for encopresis, two MAs 114,115 ; for developmental coordination disorder, one MA 116 ; and for PTSD, one MA 117 .…”

The 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders: Major depression summary

“…to provide prophylaxis. Therefore, following a depressive episode, we recommend maintaining antidepressant treatment for at least six months, and up to one year (see meta‐analysis), 49 and especially if there have been several episodes of illness 50 . Beyond one year there is modest evidence for continuing antidepressant therapy that suggests those receiving antidepressant treatment beyond 12 months (NNT 3.8 CI 3.3–4.6) have significantly fewer re‐occurrences 51 .…”

Patterns of hypnotic prescribing for residual insomnia and recurrence of major depressive disorder: a retrospective cohort study using a Japanese health insurance claims database

“…In this study, no difference in MDD recurrence was found by hypnotic drug type, suggesting that these advantages may be realized without increasing risk of depression relapse in patients with residual insomnia. However, a recent meta-analysis has reported differences in MDD relapse rates according to class of antidepressant therapy [25].…”