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.

• Authors: Anthony DeLeon, Nick C Patel, M Lynn Crismon
• Journal: Clinical therapeutics (Clin Ther) Vol. 26 Issue 5 Pg. 649-66 (May 2004) ISSN: 0149-2918 [Print] United States
• PMID: 15220010 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S., Review)

Chemical References

• Antipsychotic Agents
• Piperazines
• Quinolones
• Aripiprazole

Topics

• Antipsychotic Agents (adverse effects, pharmacology, therapeutic use)
• Aripiprazole
• Bipolar Disorder (drug therapy)
• Humans
• Piperazines (adverse effects, pharmacology, therapeutic use)
• Psychiatric Status Rating Scales
• Psychotic Disorders (drug therapy)
• Quinolones (adverse effects, pharmacology, therapeutic use)
• Randomized Controlled Trials as Topic
• Schizophrenia (drug therapy)