Effectiveness and tolerability of olanzapine in the treatment of adolescents with schizophrenia and related psychotic disorders: results from a large, prospective, open-label study.

OBJECTIVE: The aim of this study was to assess effectiveness and tolerability of oral olanzapine treatment of adolescents with schizophrenic disorders. METHOD: Adolescent patients (12-19 years) with schizophrenia, schizoaffective, or schizophreniform disorders according to the Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition (DSM-IV) were enrolled in a multicenter, prospective, open-label study. Following a 2- to 9-day washout period, patients initially received 10 mg/day olanzapine. Dose modification was allowed during week 2 (dose range 5-15 mg/day) and during weeks 3-6 (dose range, 5-20 mg/day). Responders (improvement > or =30% on the Brief Psychiatric Rating Scale, BPRS) continued olanzapine for additional 18 weeks. Psychopathology was assessed using BPRS and Clinical Global Impressions (CGI) scales; side effects were assessed by adverse event reporting. RESULTS: Out of 96 patients enrolled at 10 sites, 60 (62.5%) met response criteria at week 6. Mean BPRS total scores decreased significantly (p < 0.001) from baseline (39.2 +/- 13.4) to week 6 last observation carried forward (LOCF) (22.2 +/- 14.7). The rate of patients considered markedly ill or worse (CGI-S) decreased from 83.3% (baseline) to 37.5% (week 6, LOCF). The most common reported adverse event was weight gain (30.2%, 29/96). Three patients (3.1%) discontinued due to adverse events. CONCLUSIONS: In this study of young patients with schizophrenia, schizoaffective, or schizophreniform disorders, olanzapine treatment was associated with marked symptom improvement. As changes in weight and prolactin levels may be greater in adolescent than in adult patients, potential risks and benefits of olanzapine treatment in adolescents should be considered carefully.

A prospective 12-week study of quetiapine in adolescents with schizophrenia spectrum disorders.

OBJECTIVE: The aim of this study was to investigate the effectiveness, tolerability, and safety of quetiapine in adolescents with schizophrenia, schizophreniform, and schizoaffective disorders in a prospective open-label study. METHOD: A total of 56 subjects (all-subjects-treated, AST), ages 12-17, received 200-800 mg of quetiapine per day (forced titration to 400 mg within week 1; median study dose 600 mg/day at week 6) in Germany, 2002 through 2004. Primary outcome measure was the change of Positive and Negative Syndrome Scale (PANSS) total score (based on the intent-to-treat (ITT) population, n = 52), secondary outcome measures were changes of PANSS subscales, severity of illness, subjective wellbeing, and safety/tolerability (the latter based on the AST population). Correlates of PANSS response (=50% reduction in PANSS total score) and discontinuation due to lack of effectiveness were analyzed by Cox regression analyses. RESULTS: Twenty-seven subjects (48%) completed the study; 17 subjects (30%) were discontinued due to lack of effectiveness. A significant reduction of PANSS total score (last observation carried forward, LOCF; p < 0.0001; effect size = 0.92) and of secondary effectiveness outcomes were detected. In all, 34.6% fulfilled the PANSS response criterion, correlated with the degree of PANSS total change within week 1. Somnolence (21.4%) and fatigue (17.9%) were the most frequent adverse events. A significant mean weight gain (6.2 kg) and mean decrease in total serum thyroxine (2.5 ng/dl) were detected. CONCLUSIONS: In this sample of mostly drug-naïve patients with early-onset schizophrenia spectrum disorders, significant reductions in PANSS total and positive scores were detected. Controlled studies are needed to confirm these findings. The significant weight gain with its potentially severe medical consequences must be weighed against quetiapine's effectiveness.