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Delbert Robinson, MD; Margaret G. Woerner, PhD; Jose Ma. J. Alvir, DrPH; Robert Bilder, PhD; Robert Goldman, PhD; Stephen Geisler, MD; Amy Koreen, MD; Brian Sheitman, MD; Miranda Chakos, MD; David Mayerhoff, MD; Jeffrey A. Lieberman, MD

Arch Gen Psychiatry. 1999;56:241-247.

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.

From the Departments of Psychiatry, Hillside Hospital, Long Island Jewish Medical Center, Glen Oaks, and the Albert Einstein College of Medicine, New York, NY (Drs Robinson, Woerner, Alvir, Bilder, Goldman, and Geisler) and University of North Carolina, Chapel Hill (Drs Sheitman, Chakos, and Lieberman); and Nassau County Medical Center, East Meadow, NY (Dr Mayerhoff). Dr Koreen is in private practice in Huntington, NY.

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