Publication Bias and the Pharmaceutical Industry: The Case of Lamotrigine in Bipolar Disorder

S. Nassir Ghaemi, MD, MPH; Arshia A. Shirzadi, DO; Megan Filkowski, BA

Disclosures

Medscape J Med. 2008;10(9):211 

In This Article

Results

Two companies providing the largest number of studies were Eli Lilly and GlaxoSmithKline (GSK); an overall summary of our results is shown in Table 1 . We then focused on the results provided for the agent with the largest number of negative studies available, lamotrigine.

Examining the Lamotrigine Data

Of major US pharmaceutical companies, so far only GSK has provided data on unpublished negative studies with results that were unfavorable to their product lamotrigine (Lamictal) ( Table 2 ).

This was not a voluntary act but rather due to legal judgment brought by the state of New York after a lawsuit about paroxetine use in children.[21] Of the 9 studies with lamotrigine in bipolar disorder provided by the GSK Web site, 2 were positive and published, and supported the company's success in securing an FDA-approved indication for lamotrigine for delay of relapse in the long-term treatment of bipolar disorder patients.[22,23] Two negative studies have been published, 1 in rapid-cycling[24] and another in acute bipolar depression,[25] but both published versions emphasize positive secondary outcomes as opposed to the negative primary outcomes. A negative study in rapid cycling has not been published in detail (GW611), nor have 2 negative randomized studies in acute bipolar depression (GW 40910 and GW 603), or 2 negative randomized trials in acute mania (GW609 and GW 610). However, all of these negative studies are reported at the company Web site, which also refers to a publication[26] that briefly summarizes results from the above 5 negative studies. However, that publication provides little actual data from these negative studies; the results are much more fully provided on their Web site.

Recently, using meta-analysis, academic investigators have published the results of 5 negative studies with lamotrigine in acute bipolar depression in more detail, confirming lack of benefit for primary outcomes.[27] When pooling those 5 studies to produce a large sample of over 2000 subjects, a small effect size of depressive symptom benefit was statistically significant. However, more benefit was seen in a subgroup analysis of those with high severity of depressive symptoms.[27]

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