Despite the availability of established
antipsychotic agents for the treatment of
schizophrenia, continued unmet needs exist for effective medications with lower adverse-effect burden. The present study evaluated the efficacy, safety, and tolerability of treatment with the atypical
antipsychotic lurasidone for patients with an acute exacerbation of
schizophrenia. Patients were randomized to 6 weeks of double-blind treatment with
lurasidone 40 mg/day, 80 mg/day, or 120 mg/day, or placebo. Changes in Positive and Negative Syndrome Scale (PANSS) scores were evaluated using mixed-model repeated-measures (MMRM) analysis. Vital signs, laboratory parameters, extrapyramidal symptoms, and electrocardiogram were assessed. Treatment with
lurasidone 80 mg/day resulted in significantly greater improvement in PANSS total score compared with placebo (-23.4 versus -17.0; p < 0.05) at study endpoint (MMRM);
lurasidone 40 mg/day and 120 mg/day achieved clinically meaningful overall PANSS score reductions from baseline (-19.2 and -20.5), but not significant separation from placebo. Differences between all
lurasidone groups and placebo for changes in laboratory parameters and electrocardiographic measures were minimal.
Weight gain ≥ 7% occurred in 8.2% of patients receiving
lurasidone and 3.2% receiving placebo. Modest increases in
prolactin (median increase, 0.7 ng/mL) and extrapyramidal symptoms were observed following treatment with
lurasidone compared with placebo.
Akathisia was the most commonly reported adverse event with
lurasidone (17.6%, versus 3.1% with placebo). In this study, in which a large placebo response was observed,
lurasidone 80 mg/day, but not 40 mg/day or 120 mg/day, was statistically superior to placebo in treating acute exacerbation of chronic
schizophrenia. All
lurasidone doses were generally well tolerated.