Aripiprazole in the treatment of schizophrenia: safety and tolerability in short-term, placebo-controlled trials.

Aripiprazole is a novel antipsychotic with a unique mechanism of action. Presented here is a pooled analysis of safety and tolerability data from all completed short-term, placebo-controlled trials in schizophrenia from the aripiprazole clinical development program. Data were analyzed from five 4- to 6-week double-blind multicenter studies of patients hospitalized with acute relapse of schizophrenia or schizoaffective disorder randomized to aripiprazole (n=932), placebo (n=416), or haloperidol (n=201). Daily aripiprazole doses ranged from 2 to 30 mg. Safety assessments included adverse event (AE) reports, EPS scales, ECGs, weight, and prolactin, glucose and cholesterol levels. Aripiprazole was well tolerated, with similar AE incidence rates to placebo, and lower rates than haloperidol for akathisia, extrapyramidal syndrome and somnolence. Objective EPS assessments demonstrated no significant differences between aripiprazole and placebo on Simpson-Angus Scale (SAS) scores, no dose-dependent effects on Barnes Akathisia scores, and significant reductions in Abnormal Involuntary Movement Scale (AIMS) scores from baseline vs. placebo (p</=0.01). Haloperidol showed increased SAS and Barnes Akathisia scores over placebo (p</=0.01). There was minimal mean weight change with aripiprazole (+0.71 kg) and haloperidol (+0.56 kg), and a lack of QT(c) prolongation. Serum prolactin increased with haloperidol, but not aripiprazole. In conclusion, aripiprazole shows a favorable safety and tolerability profile with low potential for EPS, weight gain, prolactin elevation, QT(c) prolongation, and sedation. Aripiprazole's safety profile may offer benefits in schizophrenia treatment.