REVIEW OF: Henssler J et al, Lancet Psychiatry 2024;11:526–535

STUDY TYPE: Systematic review and meta-analysis

Patients stopping antidepressants sometimes struggle, but how often, and how badly? Prior estimates put the rate as high as 56%, with nearly half of those cases being severe. This meta-analysis of 79 studies covering 21,000 patients offers a more grounded answer.

Across 62 study groups, about 31% of patients stopping an antidepressant reported at least one discontinuation symptom—but so did 17% stopping placebo. The authors estimate that roughly 15% of patients experienced symptoms attributable to the drug. Severe symptoms affected 3% of those stopping an antidepressant versus less than 1% stopping placebo. Typical symptoms included dizziness, nausea, headache, irritability, insomnia, and sensory disturbances like “brain zaps.” Tapering didn’t clearly reduce incidence overall, though the heterogeneity in taper protocols makes that finding hard to interpret.

Drug choice mattered. Venlafaxine, desvenlafaxine, and imipramine had the highest chance of causing at least one symptom, as well the highest chance of causing severe symptoms. Paroxetine also ranked high for severity. Fluoxetine and sertraline had the lowest rates.

CARLAT TAKE

The headline figure—that one in three patients have discontinuation symptoms—is real, but half appears to be expectation and nonspecific effects, not pharmacology. The true drug-attributable rate is closer to one in six. Counsel patients that they likely won’t have significant symptoms, and that symptoms are usually transient. For venlafaxine, desvenlafaxine, or paroxetine, taper slowly and warn patients specifically about the higher risk of severe symptoms.