Review
Aripiprazole monotherapy in the treatment of bipolar disorder: A meta-analysis

https://doi.org/10.1016/j.jad.2010.10.018Get rights and content

Abstract

Introduction

Aripiprazole is approved for the acute and maintenance treatment of manic and mixed episodes associated with bipolar I disorder. The aim of the present work was to review and meta-analyze the findings of all the available randomized double-blind controlled trials (RCTs) on the efficacy of aripiprazole in the treatment of bipolar disorder.

Material and methods

Aripiprazole RCTs were identified with a systematic search of MEDLINE and repositories. Standard meta-analytic techniques were applied.

Results

Two thousand three hundred and three patients took part in the aripiprazole acute mania RCTs. At week 3 the pooled aripiprazole vs. placebo effect size was 0.34 and the NNT was 6 for response and 14 for remission. On average, response started at day 3. Suicide rates were negligible for all groups in mania but they were not reported in the acute depression trials. The meta-analysis of acute bipolar depression RCTs revealed a significant difference at week 8 with a weak effect size equal to 0.17. The analysis of maintenance data suggest that the median survival time for the aripiprazole group was not evaluable (very long), while the median survival time for placebo was 118–203 days depending on the clinical subpopulation.

Discussion

The current meta-analysis supports the usefulness of aripiprazole during all phases of bipolar illness. Its effect against acute bipolar depression is weak and the efficacy during the maintenance phase is proven only against new manic episodes in patients with an index manic episode who had previously responded to aripiprazole during the acute phase.

Introduction

Only during the last few years, atypical or second generation antipsychotics (SGAs) gained a position in the treatment of bipolar disorder (BD). The most recent advances in bipolar treatment concern the EMEA and the FDA approval of olanzapine, risperidone, quetiapine, ziprasidone, aripiprazole and asenapine for the treatment of acute mania, the approval of quetiapine and the olanzapine–fluoxetine combination against acute bipolar depression and the approval of olanzapine, quetiapine, ziprasidone and aripiprazole for the maintenance phase.

Aripiprazole was first approved by the Food and Drug Administration (FDA) in USA in 2002 for the treatment of schizophrenia and more recently for the treatment of bipolar disorder during the acute manic and maintenance treatment. Studies during the acute bipolar depression were negative, while maintenance studies report efficacy only in preventing manic episodes in patients that responded to aripiprazole during the acute manic phase.

The current review and meta-analysis will focus on all outcome measures of randomized controlled trial testing the efficacy of aripiprazole in bipolar disorder. There is no such analysis in the literature so far, and the reviews available (Aitchison et al., 2009, Cipriani et al., 2006, Currier et al., 2007, McIntyre et al., 2007a, McIntyre et al., 2007b, Perlis et al., 2006, Sachs et al., 2007, Sanford and Scott, 2008, Smith et al., 2007b, Suppes et al., 2008) do not include all the trials that have been conducted and instead focus on specific issues or are selective. A recent meta-analysis focusing specifically on aripiprazole (Arbaizar et al., 2009) is poor and misleading since it pools together 4 published monotherapy and 1 add-on study, does not include unpublished trials and does not report the effect size. There is a previous review paper by the authors (Fountoulakis and Vieta, 2009) and a meta-analysis specifically investigating the effect of aripiprazole on psychotic symptoms during the acute manic phase (Fountoulakis et al., 2009a).

Section snippets

Method to locate trials

The first step of the search included a key word search of the MEDLINE and the internet with the words ‘aripiprazole’ and ‘bipolar’.

The second step included the search of the BMS site (http://www.bms.com/clinical_trials/) as well as several on-line repositories including http://clinicaltrials.gov/, www.clinicalstudyresults.org/, and http://www.cochrane.org/.

The third step included the scan of the reference list of various review and meta-analysis papers.

Types of studies

The studies should be randomized and

Discussion

The current paper reports an effect size equal to 0.34 for aripiprazole against acute mania. The pooled NNT was 6 for aripiprazole vs. placebo concerning response at week 3 and equal to 14 concerning remission. The respected OR were equal to 1.16 and 1.09. The average day the response started was day 3. The switch rates were peculiarly in favour of haloperidol and against lithium, and this is in sharp contrast to the overall literature. The suicide rates were negligible for all groups. The

Role of funding source

There was no sponsor supporting the current study.

Conflict of interest

There was no sponsor supporting the current study.

Dr. Fountoulakis is member of the International Consultation Board of Wyeth for desvenlafaxine and has received grants or honoraria for lectures from AstraZeneca, Servier, Janssen-Cilag, Eli-Lilly and research grants from AstraZeneca, Janssen-Cilag, Elpen and Pfizer Foundation.

Dr. Vieta has acted as consultant, received grants, or received honoraria for lectures by the following companies: Almirall, AstraZeneca, Bial, Bristol-Myers-Squibb,

Acknowledgments

KNF has full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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