Aripiprazole in the maintenance treatment of bipolar disorder: a critical review
of the evidence and its dissemination into the scientific literature.
Author(s): Tsai AC, Rosenlicht NZ, Jureidini JN, Parry PI, Spielmans GI, Healy D.
Affiliation(s): Robert Wood Johnson Health and Society Scholars Program, Harvard University,
Cambridge, Massachusetts, United States of America.
Publication date & source: 2011, PLoS Med. , 8(5):e1000434
BACKGROUND: Aripiprazole, a second-generation antipsychotic medication, has been
increasingly used in the maintenance treatment of bipolar disorder and received
approval from the U.S. Food and Drug Administration for this indication in 2005.
Given its widespread use, we 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.
METHODS AND FINDINGS: We systematically searched multiple databases to identify
double-blind, randomized controlled trials of aripiprazole for the maintenance
treatment of bipolar disorder while excluding other types of studies, such as
open-label, acute, and adjunctive studies. We then used a citation search to
identify articles that cited these trials and rated the quality of their
citations. Our evidence search protocol identified only two publications, both
describing the results of a single trial conducted by Keck et al., which met
criteria for inclusion in this review. We describe four issues that limit the
interpretation of that trial as supporting the use of aripiprazole for bipolar
maintenance: (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
effects of treatment; and (4) a low overall completion rate. Our citation search
protocol yielded 80 publications that cited the Keck et al. trial in discussing
the use of aripiprazole for bipolar maintenance. Of these, only 24 (30%)
mentioned adverse events reported and four (5%) mentioned study limitations.
CONCLUSIONS: A single trial by Keck et al. represents the entirety of the
literature on the use of aripiprazole for the maintenance treatment of bipolar
disorder. Although careful review identifies four critical limitations to the
trial's interpretation and overall utility, the trial has been uncritically cited
in the subsequent scientific literature. Please see later in the article for the
Editors' Summary.
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