Randomized controlled trial of interventions designed to reduce the risk of progression to first-episode psychosis in a clinical sample with subthreshold symptoms

Arch Gen Psychiatry. 2002 Oct;59(10):921-8. doi: 10.1001/archpsyc.59.10.921.


Background: Most disability produced by psychotic illnesses, especially schizophrenia, develops during the prepsychotic period, creating a case for intervention during this period. However, only recently has it been possible to engage people in treatment during this phase.

Methods: A randomized controlled trial compared 2 interventions in 59 patients at incipient risk of progression to first-episode psychosis. We termed this group ultra-high risk to emphasize the enhanced risk vs conventional genetic high-risk studies. Needs-based intervention was compared with specific preventive intervention comprising low-dose risperidone therapy (mean dosage, 1.3 mg/d) and cognitive behavior therapy. Treatment was provided for 6 months, after which all patients were offered ongoing needs-based intervention. Assessments were performed at baseline, 6 months, and 12 months.

Results: By the end of treatment, 10 of 28 people who received needs-based intervention progressed to first-episode psychosis vs 3 of 31 from the specific preventive intervention group (P=.03). After 6-month follow-up, another 3 people in the specific preventive intervention group became psychotic, and with intention-to-treat analysis, the difference was no longer significant (P=.24). However, for risperidone therapy-adherent patients in the specific preventive intervention group, protection against progression extended for 6 months after cessation of risperidone use.

Conclusions: More specific pharmacotherapy and psychotherapy reduces the risk of early transition to psychosis in young people at ultra-high risk, although their relative contributions could not be determined. This represents at least delay in onset (prevalence reduction), and possibly some reduction in incidence.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antipsychotic Agents / therapeutic use*
  • Australia / epidemiology
  • Cognitive Behavioral Therapy / methods*
  • Combined Modality Therapy
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Male
  • Outcome Assessment, Health Care / statistics & numerical data
  • Prevalence
  • Psychiatric Status Rating Scales
  • Risk Factors
  • Risperidone / therapeutic use*
  • Schizophrenia / epidemiology
  • Schizophrenia / prevention & control*
  • Schizophrenia / therapy
  • Single-Blind Method


  • Antipsychotic Agents
  • Risperidone