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

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 postsynaptic dopamine(2) receptors and presynaptic autoreceptors, in addition to displaying partial agonism at serotonin(1A) receptors and antagonism at serotonin(2A) receptors. 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. 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. 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 > or =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 < or = 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. 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.