AIM: Based on previous reports of second-generation antipsychotic agents having a beneficial effect on prodromal symptoms, we investigated the effectiveness and tolerability of atypical antipsychotic therapies in individuals at high risk for developing psychosis. 

METHODS: We examined prodromal symptoms and functioning in individuals at ultra-high-risk for psychosis using an uncontrolled prospective design with pre- and post-treatment measures. 

RESULTS: Of the 27 subjects taking antipsychotics during the study period, 15 took part in at least one follow-up assessment. Overall Comprehensive Assessment of At-Risk Mental States scores significantly improved at the last evaluation point, with a medium-size effect of Cohen's d = 0.54 (95% confidence interval, -0.02 to 1.08) (mean follow-up period = 8.8; SD = 8.3 months). Depression and anxiety symptoms were markedly reduced, and global and social functioning also significantly improved. Of the 27 subjects, two (7.4%) converted to psychosis and 16 (59.3%) experienced at least one treatment-emergent adverse event, but no subjects exhibited serious adverse events. 

CONCLUSIONS: The results of this study support treating high-risk individuals with antipsychotics to reduce prodromal symptoms with adequate safety.