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

Abstract:

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 postsynaptic 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 > 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. 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.

journal_name

Clin Ther

journal_title

Clinical therapeutics

authors

DeLeon A,Patel NC,Crismon ML

doi

10.1016/s0149-2918(04)90066-5

subject

Has Abstract

pub_date

2004-05-01 00:00:00

pages

649-66

issue

5

eissn

0149-2918

issn

1879-114X

pii

S0149291804900665

journal_volume

26

pub_type

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