Aripiprazole: A comprehensive review of its pharmacology, clinical efficacy, and tolerability

Background: Recently approved for the treatment of schizophrenia, aripiprazole represents the sixth second-generation antipsychotic (SGA) introduced to the US market. Aripiprazole is considered a partial dopaminergic agonist, acting on both postynaptic dopamine 2 receptors and presynaptic autoreceptors, in addition to displaying partial agonism at serotonin 1A receptors and antagonism at serotonin 2A receptors. Objective: The aim of this study was to comprehensively review all available literature regarding the mechanism of action, pharmacokinetics, clinical efficacy, and adverse effects of aripiprazole. Methods: Relevant data were collected using MEDLINE and International Pharmaceutical Abstracts searches with the terms aripiprazole and OPC-14597 and with no limitations on year. Abstracts and posters presented at national and international scientific meetings were also reviewed. Results: Aripiprazole exhibits linear pharmacokinetics and is administered once daily. In multiple clinical trials, aripiprazole was effective in significantly reducing symptomatology associated with schizophrenia-related disorders compared with placebo ( P < 0.05). Dosages ≥15 mg/d more consistently produced significant reductions from baseline of Positive and Negative Syndrome Scale total scores ( P < 0.05) and were more likely to elicit a response than smaller dosages. Effects observed were comparable to those seen with risperidone and haloperidol, which were also significantly more effective than placebo ( P < 0.05). Aripiprazole exhibited a favorable safety and tolerability profile, with a low propensity to cause extrapyramidal symptoms, weight gain, cardiovascular abnormalities, hyperprolactinemia, hypercholesterolemia, or glucose dysregulation. Conclusions: Aripiprazole represents a well-tolerated and effective addition to the antipsychotic armamentarium. However, definitive advantages associated with dopamine partial agonism have yet to be determined. Long-term, head-to-head comparisons with other SGAs are needed to establish the effects of chronic administration and the relative safety and efficacy of aripiprazole.