Incidence of antidepressant discontinuation symptoms: a systematic review and meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis including randomized controlled trials
PubMed 38851198 · doi:10.1016/S2215-0366(24)00133-0
What was done
Authors conducted a systematic review and random-effects meta-analysis of Medline, EMBASE, and CENTRAL through October 13, 2022. They included randomized controlled trials, controlled trials, and observational studies evaluating discontinuation symptoms after stopping or tapering antidepressants or placebo in patients with mental, behavioural, or neurodevelopmental disorders. Studies in neonates and those using antidepressants for organic pain syndromes were excluded. Primary outcomes were the overall incidence of antidepressant discontinuation symptoms and the incidence of severe discontinuation symptoms.
What was found
The review analyzed 79 studies (44 RCTs, 35 observational studies) with 21,002 patients (16,532 discontinuing antidepressants, 4,470 discontinuing placebo; 72% female, mean age 45 years): - Incidence of at least one discontinuation symptom was 0.31 (95% CI 0.27–0.35) in 62 antidepressant groups versus 0.17 (95% CI 0.14–0.21) in 22 placebo groups. - In included RCTs comparing antidepressant to placebo discontinuation directly, the summary difference in incidence was 0.08 (95% CI 0.04–0.12). - Severe discontinuation symptoms occurred at an incidence of 0.028 (95% CI 0.014–0.057) after antidepressant discontinuation versus 0.006 (95% CI 0.002–0.013) after placebo discontinuation. - Desvenlafaxine, venlafaxine, imipramine, and escitalopram were linked to higher symptom frequencies; imipramine, paroxetine, and desvenlafaxine or venlafaxine were associated with higher symptom severity.
Why it matters
This meta-analysis provides large-scale benchmark rates of antidepressant discontinuation symptoms, showing that true drug-specific symptoms occur in approximately 1 in 6 to 7 patients after accounting for placebo effects, with severe symptoms remaining uncommon.
Limits
Heterogeneity across studies was substantial and not fully explained by diagnosis, medication, or trial characteristics. Observational studies comprised 35 of the 79 included papers. Ethnicity was inconsistently reported, and studies could not fully separate true discontinuation symptoms from re-emerging psychopathology or subjective patient and investigator reporting biases.
Cited by
- context SSRIs have a side effect rate of approximately 50% and a withdrawal/discontinuation effect rate of approximately 50%.