Clinical outcome after antipsychotic treatment discontinuation in functionally recovered first-episode nonaffective psychosis individuals: a 3-year naturalistic follow-up study

J Clin Psychiatry. 2016 Apr;77(4):492-500. doi: 10.4088/JCP.14m09540.


Objective: The timing of antipsychotic discontinuation in patients who have fully recovered from their initial episode of psychosis is still open to discussion. We aimed to evaluate the risk of symptom recurrence during the 3 years after antipsychotic discontinuation in a sample of functionally recovered first-episode nonaffective psychosis (FEP) patients (DSM-IV criteria) with schizophrenia spectrum disorder.

Method: Participants in this open-label, nonrandomized, prospective study were drawn from an ongoing longitudinal intervention program of FEP from a university hospital setting in Spain. From July 2004 to February 2011, functionally recovered FEP individuals were eligible if they met the inclusion criteria of (1) a minimum of 18 months on antipsychotic treatment, (2) clinical remission for at least 12 months, (3) functional recovery for at least 6 months, and (4) stabilization at the lowest effective doses for at least 3 months. Forty-six individuals who were willing to discontinue medication were included in the discontinuation group (target group). Twenty-two individuals opted to stay on the prescribed antipsychotic medication and therefore were included in the maintenance group (control group). Primary outcome measures were relapse rate at 18 and 36 months and time to relapse.

Results: The rates of relapse over the 3-year period were 67.4% (31 of 46) in the discontinuation group and 31.8% (7 of 22) in the maintenance group. The mean time to relapse was 209 (median = 122) days and 608 (median = 607) days, respectively (log rank = 10.106, P = .001). The resumption of antipsychotic medication after the relapse occurred was associated with clinical stability and lack of further relapses. When the overall group of relapsed individuals from the 2 conditions (N = 38) was compared to those who remained asymptomatic after 3 years (N = 30), there were significant differences (P < .05) in total scores on the Scale for the Assessment of Negative Symptoms, the Clinical Global Impressions scale, and the Disability Assessment Schedule.

Conclusions: Antipsychotic treatment discontinuation in individuals who had accomplished a functional recovery after a single psychotic episode was associated with a high risk of symptom recurrence. Relapsed individuals had a greater severity of symptoms and lower functional status after 3 years.

Trial registration: identifier: NCT02220504.

Publication types

  • Clinical Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / adverse effects*
  • Antipsychotic Agents / therapeutic use*
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Prospective Studies
  • Psychiatric Status Rating Scales
  • Psychotic Disorders / diagnosis
  • Psychotic Disorders / drug therapy*
  • Psychotic Disorders / psychology
  • Recurrence
  • Risk Assessment
  • Schizophrenia / diagnosis
  • Schizophrenia / drug therapy*
  • Schizophrenic Psychology
  • Substance Withdrawal Syndrome / diagnosis*
  • Substance Withdrawal Syndrome / drug therapy*
  • Substance Withdrawal Syndrome / psychology*


  • Antipsychotic Agents

Associated data