Aripiprazole in acute mania and long-term treatment of bipolar disorder: a critical review by an Italian working group.

Bipolar disorder (BD) is a chronic illness that is characterized by recurrent episodes of mania, depression or mixed symptoms. BD has a prevalence of approximately 2-4% in the general population and is associated with a substantial burden in terms of morbidity and mortality. Mania is one of the most difficult to treat manifestations of BD and antipsychotic drugs play a major therapeutic role in this respect. Acting mainly at dopamine receptors, first-generation antipsychotics are effective in controlling symptoms of BD; however, these drugs cause troublesome extrapyramidal symptoms (EPS) and hyperprolactinaemia. The more recently developed second-generation antipsychotics, which act at other receptors, provide a broader spectrum of clinical efficacy and have a more favourable tolerability profile than first-generation antipsychotics. Some second-generation antipsychotics are, however, associated with adverse effects such as weight gain and metabolic disorders, which may be cause for concern. Aripiprazole, a recently introduced second-generation antipsychotic, has a unique receptor-binding profile and mechanism of action, which are thought to account for its low propensity for weight gain, metabolic disturbances and sedation. Aripiprazole is approved in the US and in Europe for the acute management and maintenance of manic and mixed episodes associated with bipolar I disorder. In both the acute and long-term maintenance settings, clinical trials have shown aripiprazole to be clinically effective in terms of response rates, remission rates and prevention of relapse. The lack of a sedative effect does not affect the efficacy of aripiprazole in controlling mania and agitation. With both short- and long-term aripiprazole treatment, adverse event rates were similar to placebo and significantly lower than seen with comparators; one exception to this is the occurrence of EPS, which was observed more frequently in aripiprazole recipients than in patients receiving placebo, but less frequently than in patients treated with haloperidol. Aripiprazole is likely to promote treatment adherence because of its favourable tolerability profile, but more specifically focused studies are required to confirm this hypothesis. The efficacy and favourable metabolic profile of aripiprazole make it a good option in the management of acute mania and maintenance treatment, especially in an outpatient setting. Thus, aripiprazole provides clinicians with a valuable additional therapeutic option for BD. Cognizant of the lack of standardized strategies for aripiprazole dosing, switching, and prevention and management of adverse effects, an expert consensus meeting was held in Italy with the aim of producing guidelines for the use of aripiprazole in acute and long-term management of BD mania. The resulting dosage, administration and switching recommendations outlined in this report are based on empirical results from well designed aripiprazole clinical trials and clinical experience, and are in accord with the manufacturer's prescribing information. However, careful evaluation of the individual patient and a thorough risk/benefit assessment should be made prior to initiating any treatment plan.