Aripiprazole

Abstract

Aripiprazole (Abilify®) is an atypical antipsychotic indicated for the treatment of mania associated with bipolar I disorder. It is unique in its class, as it is a partial agonist of dopamine D₂ and D₃, and serotonin 5-HT_1A receptors and a modest antagonist of 5-HT_2a receptors. This article reviews the pharmacological properties, clinical efficacy and tolerability of oral aripiprazole in the management of mania associated with bipolar I disorder in adults. In well designed clinical trials in patients with recent manic or mixed episodes associated with bipolar I disorder, oral aripiprazole monotherapy or adjunctive therapy to lithium or valproate improved symptoms of mania following short-term (≤12 weeks) or maintenance (≤100 weeks) treatment. In addition, maintenance treatment with aripiprazole (as monotherapy or adjunctive therapy) prevented the recurrence of any mood episodes or manic episodes (but not depressive episodes) in patients who had previously been stabilized and maintained on aripiprazole. Aripiprazole was generally well tolerated in these studies and was associated with a low risk of prolactin elevation, corrected QT interval prolongation and metabolic disturbances. Extrapyramidal symptoms occurred in up to 28% of aripiprazole recipients, but after longer-term treatment (≤100 weeks), symptom severity did not differ significantly from that in placebo recipients. Aripiprazole treatment generally did not increase bodyweight to a clinically relevant extent; however, more patients receiving aripiprazole monotherapy than placebo had clinically significant bodyweight gain during 100 weeks’ treatment. Additionally, in a comparative trial, aripiprazole monotherapy was at least as effective as haloperidol monotherapy in terms of improving symptoms of mania, but had the advantage of a lower incidence of some adverse events, such as extrapyramidal symptom-related adverse events. Further trials comparing aripiprazole with other agents, including atypical antipsychotics, would help to definitively position aripiprazole relative to these agents. Current guidelines recommend aripiprazole as a first-line option (as monotherapy or adjunctive therapy) for the short-term treatment of mania associated with bipolar I disorder, and as a first-line (as monotherapy) or second-line (as adjunctive therapy) option for preventing the recurrence of mood episodes during longer-term therapy.