Olanzapine for the treatment of borderline personality disorder: variable dose 12-week randomised double-blind placebo-controlled study.

BACKGROUND: Despite the prevalence and clinical significance of borderline personality disorder, its treatment remains understudied. AIMS: To evaluate treatment with variably dosed olanzapine in individuals with borderline personality disorder. METHOD: In this 12-week randomised, double-blind trial, individuals received olanzapine (2.5-20 mg/day; n=155) or placebo (n=159) (trial registry: NCT00091650). The primary efficacy measure was baseline to end-point change on the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) using last-observation-carried-forward methodology. RESULTS: Both olanzapine and placebo groups showed significant improvements but did not differ in magnitude at end-point (-6.56 v. -6.25, P=0.661). Response rates (50% reduction in ZAN-BPD) were 64.7% with olanzapine and 53.5% with placebo (P=0.062); however, time to response was significantly shorter for olanzapine (P=0.022). Weight gain was significantly greater (2.86 v. -0.35 kg, P<0.001), with higher incidence of treatment-emergent abnormal high levels of prolactin for the olanzapine group. CONCLUSIONS: Individuals treated with olanzapine and placebo showed significant but not statistically different improvements on overall symptoms of borderline personality disorder. The types of adverse events observed with olanzapine treatment appeared similar to those observed previously in adult populations.

Randomized, double-blind trial of olanzapine versus placebo in patients prodromally symptomatic for psychosis.

OBJECTIVE: This study assessed the efficacy of olanzapine in delaying or preventing conversion to psychosis and reducing symptoms in people with prodromal symptoms of schizophrenia. METHOD: This randomized trial occurred at four North American clinics in the Prevention Through Risk Identification, Management, and Education project. Outpatients received olanzapine (5-15 mg/day, N=31) or placebo (N=29) during a 1-year double-blind treatment period and no treatment during a 1-year follow-up period. Efficacy measures included the conversion-to-psychosis rate and Scale of Prodromal Symptoms scores. RESULTS: During the treatment year, 16.1% of olanzapine patients and 37.9% of placebo patients experienced a conversion to psychosis, a nearly significant difference. The hazard of conversion among placebo patients was about 2.5 times that among olanzapine-treated patients, which also approached significance. In the follow-up year, the conversion rate did not differ significantly between groups. During treatment, the mean score for prodromal positive symptoms improved more in the olanzapine group than in the placebo group, and the mixed-model repeated-measures least-squares mean score showed significantly greater improvement between weeks 8 and 28 with olanzapine. The olanzapine patients gained significantly more weight (mean=8.79 kg, SD=9.05, versus mean=0.30 kg, SD=4.24). CONCLUSIONS: A significant treatment difference in the conversion-to-psychosis rate was not demonstrated. However, these results may be influenced by low power. The nearly significant differences suggest that olanzapine might reduce the conversion rate and delay onset of psychosis. Olanzapine was efficacious for positive prodromal symptoms but induced weight gain. Further treatment research in this phase of illness is warranted.

Amantadine for weight gain associated with olanzapine treatment.

Patients with schizophrenia (Sch), schizoaffective, schizophreniform, or bipolar (BP) I disorders [Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)]; not manic or acutely psychotic [Brief Psychiatric Rating Scale (BPRS) total score < or =45]; treated with olanzapine for 1-24 months; and who had gained > or =5% of their initial body weight were examined to determine whether amantadine could attenuate weight gain or promote weight loss. Olanzapine (Olz; 5-20 mg/day) was co-administered with double-blind treatment of 100-300 mg/day amantadine (Olz+Amt, n=60) or placebo (Olz+Plc, n=65). Visit-wise analysis of weight showed that weight change from baseline [last-observation-carried-forward (LOCF)] in the Olz+Amt group was significantly different from the Olz+Plc group at weeks 8 (P=0.042), 12 (P=0.029), and 16 (primary endpoint, mean+/-S.D.: -0.19+/-4.58 versus 1.28+/-4.26 kg, P=0.045). Mean BPRS total score, positive subscale, and anxiety-depression scores improved comparably in both groups, and Montgomery-Asberg Depression Rating Scale (MADRS) total score improved in the Olz+Amt group. Overall, amantadine was safe, was well tolerated, and attenuated weight gain or promoted weight loss in some patients who had gained weight during olanzapine therapy.