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

Abstract

BackgroundWell-tolerated and effective therapies for bipolar mania are required.AimsTo evaluate the efficacy and tolerability of aripiprazole as acute and maintenance of effect therapy in patients with bipolar I disorder experiencing manic or mixed episodes.MethodPatients were randomised to double-blind aripiprazole (15 or 30 mg/day; n=167) placebo (n=153) or haloperidol (5–15 mg/day, n=165) for 3 weeks (trial registration NCT00097266). Aripiprazole- and haloperidol-treated patients remained on masked treatment for 9 additional weeks.ResultsMean change in Young Mania Rating Scale Total score (primary end-point) at week 3 was significantly greater with aripiprazole (–12.0; P<0.05) and haloperidol (–12.8; P<0.01) than with placebo (–9.7). Improvements were maintained to week 12 for aripiprazole (–17.2) and haloperidol (–17.8). Aripiprazole was well tolerated. Extrapyramidal adverse events were more frequent with haloperidol than aripiprazole (53.3% v. 23.5%).ConclusionsClinical improvements with aripiprazole were sustained to week 12. Aripiprazole was generally well tolerated.

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

“…Only two studies used a dose of < 20 mg/day, thus precluding meta-analysis (Findling et al, 2009;Tramontina et al, 2009). Across three RCTs, no significant difference between aripiprazole (n = 403 in three arms) and placebo (n = 387 in three arms) was noted in the > 20 mg/day group (Findling et al, 2009;Sachs et al, 2006;Young et al, 2009) (Hedges' g: -0.097, 95% CI: -0.279 to 0.086, p = 0.299).…”

“…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.…”

“…Among the 20 eligible articles, two investigated the efficacy of aripiprazole monotherapy in comparison with haloperidol (Vieta et al, 2005;Young et al, 2009) (aripiprazole participants = 340; haloperidol participants = 337). 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).…”

“…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). …”

“…It has shown beneficial effects in patients with schizophrenia and possibly in mood disorders including BD, including good tolerability in patients with schizophrenia (Oya et al, 2015), good efficacy in patients with acute mania (Fountoulakis et al, 2011;Young et al, 2009), and good efficacy in preventing relapses (Marcus et al, 2011), although there is limited evidence regarding bipolar…”