Randomized controlled trial of interventions for young people at ultra high risk for psychosis

OBJECTIVE: Cognitive therapy and/or low-dose antipsychotic administered during the prodromal phase of schizophrenia may prevent or delay the onset of full-blown illness. However, it is unclear which of these treatments are most effective, how long treatment should be given, and whether effects will be sustained over a prolonged period. METHOD: In order to examine these issues, we conducted a randomized controlled trial of cognitive therapy + risperidone; cognitive therapy + placebo; and supportive therapy + placebo in young people at ultra high risk for developing a psychotic disorder (that is, putatively prodromal). The main outcome was transition to psychotic disorder, with level of symptoms and functioning the secondary outcomes. This article reports the interim 6-month follow-up results. The study was conducted from August 2000 to May 2007. RESULTS: Of a possible 464 eligible ultra high risk individuals, 115 were recruited to the randomized controlled trial (cognitive therapy + risperidone, n = 43; cognitive therapy + placebo, n = 44; and supportive therapy + placebo, n = 28). An additional 78 individuals agreed to follow-up assessments but not to randomization ("monitoring group," n = 78). At 6 months, 8 of the 115 participants (7.0%) and 4 of the monitoring group (5.1%) had developed psychotic disorder. There were no significant differences between the 3 randomized groups (log rank test, P = .92) or between all 4 groups (log rank test, P = .93). There was also no difference between the 4 groups in secondary measures, with all groups showing a reduction in symptoms and increased functioning. CONCLUSIONS: Rates of transition to psychosis were lower than expected, particularly in the control supportive therapy + placebo group. This may have accounted for the negative finding, as the sample was therefore underpowered to find any difference between groups. Alternatively, it may be that all treatments were equally effective or equally ineffective at 6 months. TRIAL REGISTRATION: http://www.anzctr.org.au Identifier: ACTRN012605000247673