Predictors of relapse following response from a first episode of schizophrenia or schizoaffective disorder

Arch Gen Psychiatry. 1999 Mar;56(3):241-7. doi: 10.1001/archpsyc.56.3.241.


Background: We examined relapse after response to a first episode of schizophrenia or schizoaffective disorder.

Methods: Patients with first-episode schizophrenia were assessed on measures of psychopathologic variables, cognition, social functioning, and biological variables and treated according to a standardized algorithm. The sample for the relapse analyses consisted of 104 patients who responded to treatment of their index episode and were at risk for relapse.

Results: Five years after initial recovery, the cumulative first relapse rate was 81.9% (95% confidence interval [CI], 70.6%-93.2%); the second relapse rate was 78.0% (95% CI, 46.5%-100.0%). By 4 years after recovery from a second relapse, the cumulative third relapse rate was 86.2% (95% CI, 61.5%-100.0%). Discontinuing antipsychotic drug therapy increased the risk of relapse by almost 5 times (hazard ratio for an initial relapse, 4.89 [99% CI, 2.49-9.60]; hazard ratio for a second relapse, 4.57 [99% CI, 1.49-14.02]). Subsequent analyses controlling for antipsychotic drug use showed that patients with poor premorbid adaptation to school and premorbid social withdrawal relapsed earlier. Sex, diagnosis, obstetric complications, duration of psychotic illness before treatment, baseline symptoms, neuroendocrine measures, methylphenidate hydrochloride challenge response, neuropsychologic and magnetic resonance imaging measures, time to response of the initial episode, adverse effects during treatment, and presence of residual symptoms after the initial episode were not significantly related to time to relapse.

Conclusions: There is a high rate of relapse within 5 years of recovery from a first episode of schizophrenia and schizoaffective disorder. This risk is diminished by maintenance antipsychotic drug treatment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / therapeutic use*
  • Cohort Studies
  • Female
  • Fluphenazine / administration & dosage
  • Fluphenazine / therapeutic use
  • Follow-Up Studies
  • Hallucinations / diagnosis
  • Hallucinations / epidemiology
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Neuropsychological Tests
  • Patient Compliance
  • Pregnancy
  • Pregnancy Complications / diagnosis
  • Pregnancy Complications / epidemiology
  • Probability
  • Psychiatric Status Rating Scales / statistics & numerical data
  • Psychotic Disorders / diagnosis
  • Psychotic Disorders / drug therapy*
  • Psychotic Disorders / prevention & control
  • Risk Factors
  • Schizophrenia / diagnosis
  • Schizophrenia / drug therapy*
  • Schizophrenia / prevention & control
  • Schizophrenic Psychology
  • Secondary Prevention
  • Severity of Illness Index
  • Sex Factors
  • Treatment Outcome


  • Antipsychotic Agents
  • Fluphenazine