How reviews covered the unfolding scientific story of gabapentin for bipolar disorder

Despite the lack of randomized controlled trials (RCTs), gabapentin use increased rapidly in the 1990s for mental health conditions. Subsequent RCTs did not demonstrate efficacy for bipolar disorder (BD). We examined the characteristics of review articles to determine their potential role in the growth of gabapentin for BD.

We searched MEDLINE, the International Pharmaceutical Abstracts and LexisNexis for review articles or commentaries examining the role of gabapentin for BD. Electronic searches were supplemented by manual searches of reference lists. Articles were abstracted for the types of evidence cited, source of evidence, the proportion of available RCTs cited and narrative blurbs discussing the role of gabapentin for BD. Review articles were classified as narrative versus systematic and positive, neutral or negative regarding the role of gabapentin in BD.

We included 27 review articles published between 1998 and 2008, but no commentaries met eligibility criteria. Most did not describe potential conflicts of interest or a funding source, and the 3 systematic reviews were of low quality. The 11 reviews published prior to the first RCT of gabapentin for BD cited uncontrolled trials or case series (n=9), basic science (n=6), chart reviews (n=3) or unpublished RCTs (n=2). Six recommended gabapentin, 3 were neutral and 2 were negative. The 16 articles published after the first gabapentin RCT continued to cite uncontrolled trials and basic science; only 5 cited all the available RCTs. However, more of these reviews (n=10) reached negative conclusions about the role of gabapentin for BD.

Narrative and low-quality systematic reviews, principally those published prior to RCTs, may have contributed to the growth of gabapentin use for BD. High-quality systematic reviews are needed to inform clinicians and policymakers about the effectiveness of new treatments.