Relapse trajectories and antipsychotic discontinuation in schizophrenia from individual participant data of five trials from the Yale Open Data Access database: a meta-analysis
Abstract
Background: Antipsychotics reduce risk of relapse in schizophrenia, but longer-term use is associated with adverse effects, often prompting dose reduction or discontinuation. Although discontinuation increases relapse risk, the clinical course is heterogeneous. Rapid relapse following antipsychotic discontinuation has been observed in clinical trials and could reflect a direct pharmacological consequence of stopping medication, as opposed to re-emergence of underlying illness. We aimed to identify distinct trajectories of symptom change preceding relapse, to examine whether trajectory membership was associated with treatment arm and baseline clinical characteristics, and to compare symptom profiles at time of relapse between individuals whose illness relapsed following discontinuation and those whose illness relapsed during continued treatment.
Methods: For this meta-analysis, on May 4, 2025, we searched the Yale University Open Data Access project database for randomised, double-blind, discontinuation trials of antipsychotics in individuals with schizophrenia or schizoaffective disorder. No language restrictions were applied. We included double-blind, placebo-controlled, relapse-prevention, randomised trials of antipsychotic medications. Studies with available individual participant data were included if participants were first treated with antipsychotic drugs for more than 3 months and clinically stabilised before they were randomly assigned to placebo (discontinuation) or…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 271 participants or records.
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