Aripiprazole in the treatment of acute manic or mixed episodes in patients with bipolar I disorder: a 3-week placebo-controlled study

Abstract

This study compares the efficacy, safety, and tolerability of a partial dopamine agonist, aripiprazole, with placebo in the treatment of patients with bipolar I disorder experiencing an acute manic or mixed episode. In total, 272 hospitalized patients were randomized to aripiprazole 30 mg/day or placebo in this 3-week, double-blind, placebo-controlled trial. Dosing could be reduced to 15 mg/day for tolerability and, subsequently, increased to 30 mg/day based on clinical response. Primary efficacy measure was mean change from baseline to endpoint in Young Mania Rating Scale (YMRS) total score; response was defined as > or = 50% decrease from baseline YMRS score. Aripiprazole-treated patients demonstrated significantly greater improvement from baseline to endpoint in mean YMRS total scores compared with placebo-treated patients as early as Day 4 and sustained through Week 3. A significantly higher response rate was observed in aripiprazole-treated patients (53% vs. 32% at endpoint). Aripiprazole produced significantly greater improvements from baseline on other efficacy assessments compared with placebo, including Clinical Global Impression - Bipolar Version Severity and Improvement scores. The 30 mg/day dose was maintained by 85% of aripiprazole-treated patients. Incidence of discontinuations due to adverse events was similar for aripiprazole (8.8%) and placebo (7.5%). Aripiprazole treatment resulted in no significant difference from placebo in change in mean body weight and was not associated with elevated serum prolactin or QTc prolongation. In conclusion, aripiprazole demonstrated superior efficacy to placebo in the treatment of patients with bipolar I disorder presenting with acute manic or mixed episodes, and exhibited a favourable safety and tolerability profile.

Aripiprazole monotherapy in acute mania: 12-week randomised placebo- and haloperidol-controlled study

“…Aripiprazole was generally well tolerated over the entire 12-week study, with an adverse event profile similar to that seen in previous short-term 6,7 and long-term studies. 8,9 The incidence of adverse events related to extrapyramidal symptoms with haloperidol was more than double that with aripiprazole, as was the use of concomitant medications for the potential treatment of such symptoms.…”

“…21,22 In previous studies, aripiprazole was started at 30 mg/day, 6,7 whereas this study demonstrated the efficacy of aripiprazole with a treatment regimen starting at 15 mg/day. As 42% of aripiprazoletreated patients were on 15 mg/day at week 3, this study demonstrated that a treatment regimen with a starting dose of 15 mg/ day can be an effective approach for treating patients with acute bipolar mania.…”

Efficacy, safety and tolerability of aripiprazole in bipolar disorder: An updated systematic review and meta-analysis of randomized controlled trials

“…We did not perform further subgroup meta-analysis of trials with adults only as fewer than three datasets were available (Sachs et al, 2006;Young et al, 2009). We divided the trials into two categories by daily dosage (< 20 mg/day and > 20 mg/day) to evaluate whether or not there was a dose-dependent effect.…”

“…Therefore, 20 articles were eligible for the current meta-analysis (Carlson et al, 2012;El-Mallakh et al, 2012;El Mallakh et al, 2010;Findling et al, 2013;Findling et al, 2009;Findling et al, 2012;Jeong et al, 2012;Kanba et al, 2014;Keck et al, 2007;Keck et al, 2003;Keck et al, 2009;Muzina et al, 2008;Quante et al, 2010;Sachs et al, 2006;Thase et al, 2008;Tramontina et al, 2009;Vieta et al, 2005;Vieta et al, 2008;Woo et al, 2011;Young et al, 2009) (Table 1). …”

“…One article (Keck et al, 2009) compared aripiprazole monotherapy and lithium in the acute phase of illness (aripiprazole = 155; lithium = 160), another article (El-Mallakh et al, 2012) compared aripiprazole monotherapy versus lithium in the maintenance stage (aripiprazole = 25; lithium = 38), and another article (Jeong et al, 2012) investigated the combination of aripiprazole with valproic acid versus haloperidol with valproic acid (aripiprazole = 28; haloperidol = 14). The remaining 15 articles (Carlson et al, 2012;El Mallakh et al, 2010;Findling et al, 2013;Findling et al, 2009;Findling et al, 2012;Kanba et al, 2014;Keck et al, 2007;Keck et al, 2003;Muzina et al, 2008;Quante et al, 2010;Sachs et al, 2006;Thase et al, 2008;Tramontina et al, 2009; A C C E P T E D M A N U S C R I P T …”