Aripiprazole: maintenance treatment for bipolar disorder. Where’s the evidence?


Aripiprazole is a second-generation antipsychotic that is widely used as a maintenance treatment for bipolar disorder in the US. It was approved by the FDA as a drug for this purpose in 2005.

A new systematic review, published in the online journal PLOS medicine, sought to critically review the evidence supporting the use of aripiprazole in the maintenance treatment of bipolar disorder and examine how that evidence has been disseminated in the scientific literature.  The authors searched multiple databases (including citation indexes) for RCTs but found only two relevant publications, both of which derive their results from a single trial by Keck et al.

The Keck trial has a number of limitations:

  1. insufficient duration to demonstrate maintenance efficacy;
  2. limited generalizability due to its enriched sample;
  3. possible conflation of iatrogenic adverse effects of abrupt medication discontinuation with beneficial effectsof treatment; and
  4. a low overall completion rate.

Despite this, the review found 80 studies that cited the Keck trial in discussing the use of aripiprazole for bipolar maintenance, although the vast majority of these studies did not mention reported side effects or the limitations of the Keck trial.

The Editor’s summary concludes:

This evaluation of the evidence base supporting the use of aripiprazole for the maintenance treatment of bipolar disorder shows that the justification for this practice relies on the results of one published trial. Moreover, the methodology and reporting of this trial mean that its results cannot easily be generalized to inform the treatment of most patients with bipolar disorder. Worryingly, the researchers’ citation search indicates that the Keck trial has been cited uncritically in the ensuing scientific literature. Although the unique features of bipolar disorder make it hard to undertake controlled studies of treatment options, the researchers express concern that “the publication and apparently uncritical acceptance of this trial may be diverting patients away from more effective treatments”.


Tsai AC, Rosenlicht NZ, Jureidini JN, Parry PI, Spielmans GI, Healy D. Aripiprazole in the maintenance treatment of bipolar disorder: a critical review of the evidence and its dissemination into the scientific literature. PLoSMed. 2011 May;8(5):e1000434.

Keck PE Jr, Calabrese JR, McIntyre RS, McQuade RD, CarsonWH, Eudicone JM, Carlson BX, Marcus RN, Sanchez R;Aripiprazole Study Group. Aripiprazole monotherapy for maintenance therapy in bipolar I disorder: a 100-week,double-blind study versus placebo. J Clin Psychiatry. 2007 Oct;68(10):1480-91. [PubMed abstract]

Note: A NICE technology appraisal is currently underway to assess the suitability of aripiprazole for the treatment and prevention of acute manic and mixed episodes in bipolar disorder in children and adolescents.

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Andre Tomlin

Andre Tomlin

André started the Mental Elf website in May 2011. He has worked as an Information Scientist in Mental Health since the late nineties; initially at Oxford University's Centre for Evidence-Based Mental Health and since 2002 as the Managing Director of Minervation Ltd. He loves blogging, social media and elves! He also has established interests in evidence-based healthcare, usability testing and web design.

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