A double-blind, randomized comparative study of aripiprazole and olanzapine in patients with schizophrenia.

BACKGROUND: Few studies have directly compared the efficacy and tolerability of atypical agents.

METHODS: This multicenter, randomized, double-blind study compared the efficacy and tolerability of aripiprazole (n = 355) with olanzapine (n = 348) in patients with schizophrenia experiencing acute relapse. After a 6-week acute treatment phase, patients with Clinical Global Impression-Improvement = 1-3 or > or = 20% reduction in the Positive and Negative Symptom Scale (PANSS) Total score could progress to the 46-week outpatient extension phase. Co-primary study objectives were to compare efficacy at Week 6 and weight gain liability from baseline to Week 26.

RESULTS: The mean olanzapine dose was 15.4 mg/day compared with a mean aripiprazole dose of 23.0 mg/day. More patients treated with olanzapine (47%) completed the 52-week study than those treated with aripiprazole (39%); time to discontinuation was significantly in favor of olanzapine (p < .05). At Week 6, mean change in PANSS Total score (olanzapine, -29.5; aripiprazole, -24.6 [random regression model]) showed a treatment difference of 4.9 points. As the pre-specified non-inferiority margin (6 points) was within the 95% confidence interval (2.2-7.6) for treatment difference, olanzapine proved to be superior to aripiprazole on this measure. More patients experienced significant weight gain at Week 26 with olanzapine (40%) than with aripiprazole (21%; p < .05 [weighted generalized estimating equation analysis]), with significant differences observed from Week 3. Mean weight gain at Week 26 was significantly greater with olanzapine than with aripiprazole (+4.30 kg vs. +.13 kg, respectively).

CONCLUSIONS: Olanzapine had a statistically significant efficacy advantage over aripiprazole, whereas aripiprazole was associated with significantly less weight gain.