However, functional levels remained relatively unchanged, which may indicate that more intensive or longer duration of intervention is needed to elevate global functioning. These findings suggest that short-term treatment can delay psychosis. The authors conclude that the number needed to treat (NNT) of four (ie, four individuals would need to be treated in order to prevent conversion in one) supports continued prodromal trial research. More clarity is expected from a 12-month, randomized, controlled trial initiated in the PACE clinic in 2000, in which risperidone plus CBT will be compared Inhibitors,research,lifescience,medical with placebo plus CBT, and with placebo plus befriending. PRIME clinic randomized double-blind

study McGlashan et al44 at Yale initiated the first double-blind, placebo trial for prodromal patients in 1997. After additional sites were added, 60 subjects were enrolled in the project with 30 randomized to receive olanzapine Inhibitors,research,lifescience,medical (5 to 15 mg) and 29 to receive placebo. Medication or placebo was given for 1 year and patients were followed for Inhibitors,research,lifescience,medical an additional year. Inclusion criteria were based on the Yung UHR categories, but operationalized by the PRIME prodromal assessment tool, the Scale of Prodromal Symptoms (SOPS).48,49 Conversion to check details psychosis, defined by this group as any positive symptom at psychotic intensity on SQPS that was of sufficient frequency duration, or was seriously disorganizing

or dangerous, warranted removal from the trial and open-label olanzapine was initiated for 6 months. Supportive psychosocial interventions were available for all patients, but effort was made to limit the use

of concomitant psychoactive medications. Inhibitors,research,lifescience,medical Results analyzed by principal mixed-effects model after 8 weeks of treatment revealed that the olanzapine Inhibitors,research,lifescience,medical group showed significant improvement from baseline on SOPS total score, positive symptom scale, negative symptom scale, and disorganized symptom scale. The placebo group did not show any significant change on any scale at any time point. Olanzapine versus placebo group differences were found by week 8 on the SOPS total, negative, and disorganized scales, but not the positive symptom scale. Positive and Negative Symptoms Scale (PANSS) total and positive symptom scores also showed significant differences between the olanzapine and placebo groups. Weight gain was the only side effect reported significantly more no often in the olanzapine group, with over 50% of this group gaining more than 7% of their baseline body weight (versus 3% in placebo group).36 Patients receiving olanzapine showed significant within-group improvements on positive symptom scores and a trend toward greater improvement when compared to the placebo group, demonstrating the efficacy of olanzapine over placebo in the treatment of attenuated positive symptoms.