Aripiprazole monotherapy in patients with rapid-cycling bipolar I disorder: an analysis from a long-term, double-blind, placebo-controlled study

Abstract

Aims Rapid-cycling bipolar disorder is difficult to treat and associated with greater morbidity than non-rapid-cycling disease. This post hoc analysis evaluated 28 patients with rapid-cycling bipolar I disorder from a 100-week, double-blind, placebo-controlled study assessing long-term efficacy, safety and tolerability of aripiprazole in patients with bipolar I disorder (most recently manic/mixed). Methods Following ≥ 6 consecutive weeks’ stabilisation with open-label aripiprazole, patients were randomised (1 : 1) to aripiprazole or placebo. Patients completing 26 weeks treatment without relapse could continue for a further 74 weeks. Primary end-point was time to relapse for manic, mixed or depressive symptoms, defined as discontinuation due to lack of efficacy. Safety assessments included adverse event (AE) monitoring and changes in weight and lipid, glucose and prolactin levels. Results Of the 28 patients (aripiprazole, n = 14; placebo, n = 14) with rapid-cycling bipolar disorder, 12 (aripiprazole, n = 7; placebo, n = 5) completed the initial 26-week treatment period and three (all aripiprazole treated) completed the 100-week, double-blind period. Time to relapse was significantly longer with aripiprazole vs. placebo at week 26 [log-rank p = 0.033; 26-week hazard ratio = 0.21 (95% CI: 0.04, 1.03)] and week 100 [log-rank p = 0.017; 100-week hazard ratio = 0.18 (95% CI: 0.04, 0.88)]. The most commonly reported AEs with aripiprazole during the 100 weeks (≥ 10% incidence and twice placebo) were anxiety ( n = 4), sinusitis ( n = 4), depression ( n = 3) and upper respiratory infection ( n = 3). One aripiprazole-treated patient discontinued due to an AE (akathisia). There were no significant between-group differences in mean changes in weight or metabolic parameters. Conclusion In this small, post hoc subanalysis, aripiprazole maintained efficacy and was generally well tolerated in the long-term treatment of rapid-cycling bipolar disorder. Further research with prospectively designed and adequately powered trials is warranted.

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

“…In these studies, the total relapse rates were significantly lower in the aripiprazole group than in the placebo group in the study by Keck et al (2007) (33% in the aripiprazole group and 52% in the placebo group) (Keck et al, 2007), and in the study by Muzina et al the time to relapse was significantly longer in the aripiprazole group than in the placebo group at week 100 (hazard ratio = 0.18, log-rank p = 0.017) (Muzina et al, 2008). …”

“…Few studies (Fountoulakis et al, 2011) (Keck et al, 2009;Muzina et al, 2008) showed promising efficacy of aripiprazole. Therefore, it may be more appropriate to use relapse rates as the primary outcome in the maintenance phase than in the acute phase in clinical practice, because the maintenance phase has a longer period of follow-up than the acute phase.…”

“…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 …”

“…We could not perform further meta-analysis of total relapse rate in the maintenance stage of aripiprazole monotherapy and placebo monotherapy because only two studies contained relevant data (Keck et al, 2007;Muzina et al, 2008). In these studies, the total relapse rates were significantly lower in the aripiprazole group than in the placebo group in the study by Keck et al (2007) (33% in the aripiprazole group and 52% in the placebo group) (Keck et al, 2007), and in the study by Muzina et al the time to relapse was significantly longer in the aripiprazole group than in the placebo group at week 100 (hazard ratio = 0.18, log-rank p = 0.017) (Muzina et al, 2008).…”

“…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). …”