Risk Factors for Psychotic Relapse After Dose Reduction or Discontinuation of Antipsychotics in Patients With Chronic Schizophrenia: A Systematic Review and Meta-analysis

High doses of antipsychotics in patients with chronic schizophrenia might lead to more severe side effects and possibly hamper recovery, but dose reduction carries the risk of psychotic relapse. It would be helpful to establish risk factors for relapse during dose reduction. We systematically searched MEDLINE, EMBASE, and PsycINFO from January 1950 through June 2019 and reviewed studies that reported on relapse rates (event rates [ERs]) after dose reduction or discontinuation of antipsychotics in cohorts of patients with chronic schizophrenia. We calculated ERs (with 95% CIs) per personyear and sought to identify potential risk factors, such as patient characteristics, dose reduction/discontinuation characteristics, and study characteristics. Of 165 publications, 40 describing dose reduction or discontinuation in 46 cohorts (1677 patients) were included. The pooled ER for psychotic relapse was 0.55 (95% CI 0.46- 0.65) per person-year. The ER was significantly higher in inpatients, patients with a shorter duration of illness, patients in whom antipsychotics were discontinued or in whom the dose was reduced to less than 5 mg haloperidol equivalent, studies with a short follow-up or published before 1990, and studies in which relapse was based on clinical judgment (ie, rating scales were not used). Clinicians should consider several robust risk factors for psychotic relapse in case of dose reduction in chronic schizophrenia.