ReviewAripiprazole monotherapy in the treatment of bipolar disorder: A meta-analysis
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al., 2009) is poor and misleading since it pools together 4 published monotherapy and 1 add-on study, does not include unpublished trials and does not report the effect size.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.
References (51)
- et al.
Aripiprazole in major depression and mania: meta-analyses of randomized placebo-controlled trials
Gen. Hosp. Psychiatry
(2009) - et al.
Spanish version of a scale for the assessment of mania: validity and reliability of the Young Mania Rating Scale
Med. Clin. (Barc.)
(2002) - et al.
Development and reliability of the HAM-D/MADRS interview: an integrated depression symptom rating scale
Psychiatry Res.
(2006) - et al.
Aripiprazole monotherapy in the treatment of acute bipolar I mania: a randomized, double-blind, placebo- and lithium-controlled study
J. Affect. Disord.
(2009) - et al.
Validation of the Spanish versions of the Montgomery–Asberg depression and Hamilton anxiety rating scales
Med. Clin. (Barc.)
(2002) - et al.
Modification of the Clinical Global Impressions (CGI) Scale for use in bipolar illness (BP): the CGI-BP
Psychiatry Res.
(1997) - et al.
Efficacy and safety of aripiprazole in subpopulations with acute manic or mixed episodes of bipolar I disorder
J. Affect. Disord.
(2008) - et al.
A meta-analysis of the use of typical antipsychotic agents in bipolar disorder
J. Affect. Disord.
(2001) - et al.
A UK consensus on the administration of aripiprazole for the treatment of mania
J. Psychopharmacol.
(2009) - et al.
Aripiprazole augmentation in major depressive disorder: a double-blind, placebo-controlled study in patients with inadequate response to antidepressants
CNS Spectr.
(2009)
Pharmacological interventions for the prevention of relapse in bipolar disorder: a systematic review of controlled trials
J. Psychopharmacol.
Aripiprazole in refractory depression?
J. Clin. Psychopharmacol.
Haloperidol alone or in combination for acute mania
Cochrane Database Syst. Rev.
Olanzapine in long-term treatment for bipolar disorder
Cochrane Database Syst. Rev.
Intramuscular aripiprazole in the control of agitation
J. Psychiatr. Pract.
The Montgomery–Asberg Depression Scale: reliability and validity
Acta Psychiatr. Scand.
Translation and validation of a French version of the Young Mania Rating Scale (YMRS)
Encephale
Efficacy and safety of aripiprazole in the treatment of bipolar disorder: a systematic review
Ann. Gen. Psychiatry
Treatment of psychotic symptoms in bipolar disorder with aripiprazole monotherapy: a meta-analysis
Ann. Gen. Psychiatry
Treatment of psychotic symptoms in bipolar disorder with aripiprazole monotherapy: a meta-analysis
Ann. Gen. Psychiatry
Role of aripiprazole in treating mood disorders
Expert Rev. Neurother.
Long-term lithium therapy for bipolar disorder: systematic review and meta-analysis of randomized controlled trials
Am. J. Psychiatry
Lamotrigine for treatment of bipolar depression: independent meta-analysis and meta-regression of individual patient data from five randomised trials
Br. J. Psychiatry
Latest maintenance data on lithium in bipolar disorder
Eur. Neuropsychopharmacol.
Methods of Meta-Analysis: Correcting Error and Bias in Research Findings
Cited by (45)
Pharmacodynamic properties of lumateperone and its efficacy in acute bipolar depression: a mechanistic hypothesis based on data
2024, European NeuropsychopharmacologyAntidepressant efficacy of cariprazine in bipolar disorder and the role of its pharmacodynamic properties: A hypothesis based on data
2023, European NeuropsychopharmacologyBipolar Disorder
2022, Comprehensive PharmacologyClinically relevant response and remission outcomes in cariprazine-treated patients with bipolar I disorder
2018, Journal of Affective DisordersEfficacy, safety and tolerability of aripiprazole in bipolar disorder: An updated systematic review and meta-analysis of randomized controlled trials
2017, Progress in Neuro-Psychopharmacology and Biological PsychiatryCitation Excerpt :Aripiprazole, a novel antipsychotic agent combining partial agonist activity at dopamine-2 (D2), dopamine-3 (D3), and serotonin-1A (5-HT1A) receptors with antagonist activity at serotonin-2A (5-HT2A) and D2 receptors (Burris et al., 2002; Jordan et al., 2002). 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 depression (Vieta et al., 2010). Aripiprazole is known to have a beneficial metabolic profile, which is an important consideration given that these patients are at an increased risk of cardiometabolic disorders (Vancampfort et al., 2016, 2015), although it may be associated with akathisia.
A meta-analysis of efficacy and safety of aripiprazole in adult and pediatric bipolar disorder in randomized controlled trials and observational studies
2016, Journal of Affective DisordersCitation Excerpt :Fountoulakis et al. (2009) supported the usefulness of ARP in the treatment of the psychotic symptoms during the acute manic and maintenance phases. Moreover, Fountoulakis et al. (2011) and Arbaizar et al. (2009) evaluated the efficacy of ARP in the treatment of BD, as monotherapy and as monotherapy add-on, respectively. In Fountoulakis et al. (2011) ARP resulted to be useful during all phases of bipolar illness, although its effect against acute bipolar depression was weak and during the maintenance phase was proven only in manic patients who responded to ARP during the acute phase.