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Systematic reviews have become a common method of synthesizing literature to examine the comparative effectiveness of medical interventions. Groups such as the Cochrane Collaboration and the U.S. Agency for Healthcare Research and Quality (AHRQ) conduct dozens of such reviews each year. However, these documents are often hundreds of pages long and the intended audiences, including medical providers and payers, may have difficulty interpreting the often technical terminology used in these reports. In this article, we describe the derivation of "key concepts" on the efficacy of antiepileptic drugs (AEDs) in the treatment of bipolar disorder from a pre- viously published systematic review of the use of AEDs (AED Review) for multiple indications, including mood disorders and chronic pain. With the aid of a multidisciplinary science panel, we derived the key concepts from the source report and subsequent updates of that report. Because we found that the key concepts were still quite technical, we subsequently derived four less technical "key messages" and revised these through multiple additional iterations. The concepts and messages were then tested with key informants and focus groups. At all stages of the process, we found that it was critical to maintain fidelity to the initial systematic review. The structured approach used in the derivation process described here proved to be very helpful in developing key messages and concepts.

Bipolar disorder is characterized by chronic and recurrent symptoms including mania, hypomania, and depressive and mixed episodes, with approximately 5.7 million Americans over age 18, or 2.6% of the U.S. population, suffering from the illness. The prevalence of the disorder may be higher due to its chronic and recurrent nature. Individuals with bipolar disorder often first present in general medical settings with depressive symptomatology. Long-term management typically occurs in mental health settings by psychiatrists or other mental health specialists. While there have been major advances in pharmacotherapy for bipolar disorder, evidence-based information on drug effectiveness is not always easily accessible to prescribers in daily practice. Available information has sometimes led to inappropriate use of various classes of drugs, specifically antiepileptic drugs (AEDs), for bipolar disorder. Originally approved in 1993 by the U.S. Food and Drug Administration (FDA) only for adjunctive treatment of partial complex seizures, the manufacturer of gabapentin (Neurontin), an AED, promoted its off-label use for treatment of psychiatric disorders, including bipolar disorder. The efficacy of the drug for this indication had not been demonstrated, nor had the manufacturer sought FDA approval for the indication. In 2004, 50 Attorneys General settled consumer protection claims regarding alleged deceptive off-label marketing practices of Pfizer subsidiary Warner-Lambert. At about the same time, a consortium of State Medicaid agencies funded a drug class review to compare effectiveness and adverse event profiles of AEDs in the treatment of bipolar mood disorder, neuropathic pain, and fibromyalgia. This article presents a summary of the findings from the drug class review related to prescription of the AEDs in bipolar disorder.

Evidence from drug class reviews is often not accessible to practicing clinicians nor is it presented in a way that allows clinicians to use the information to guide treatment and prescribing decisions. Nevertheless, information from such reviews can be very helpful to clinicians as they evaluate the "evidence" provided to them through marketing strategies implemented, primarily, by the pharmaceutical industry and designed to influence their prescribing behavior. Unfortunately, these marketing strategies can be used to promote the off-label use of drugs that may not be efficacious. One example is the pharmaceutical marketing to promote off-label use of gabapentin (Neurontin) for the treatment of bipolar disorder, the legality of which was later addressed in a major lawsuit by the National Association of Attorneys General. We describe an effort to use counter-marketing strategies to compete with those implemented by the pharmaceutical industry and to help clinicians, principally psychiatrists, make use of available evidence to inform their prescription of antiepileptic drugs (AEDs) in the treatment of bipolar disorder. A growing body of literature describes industry marketing practices designed to influence prescriber behavior. This literature suggests that use of competing approaches involving the same underlying strategies to deliver highly credible information from trusted sources can inform prescriber knowledge and prescribing practice. We describe our use of existing evidence to develop accurate and convincing messages and materials to be disseminated nationally to counter industry misinformation and promote evidence-based prescription of AEDs.

BACKGROUND Bipolar disorder is a common and debilitating psychiatric illness. Several antiepileptic drugs (AEDs) have been approved for the treatment of bipolar disorder. Gabapentin gained a large market share of AED use in the late 1990s in spite of a lack of randomized clinical trial (RCT) evidence and no labeled indication from the U.S. Food and Drug Administration for its use in psychiatric illness. This article describes the results of a literature review, the purpose of which was to examine the characteristics of studies conducted in humans concerning the efficacy of gabapentin in bipolar disorder. Methods. Publications relevant to this topic were identified based on a PUBMED search as well as an examination of references from a published systematic review and citations from relevant review articles. Results. The search located 29 studies published between 1997 and 2007, with the greatest number of articles published in 1998 and 1999. Of these 29 publications, 15 involved uncontrolled case series, while 6 were single case reports. The sample size in the studies was generally small, and often we could not identify the funding source. Despite the generally weak study design in the identified publications, the authors of the articles often commented on the promising nature of gabapentin therapy for bipolar disorder. However, 4 small, randomized trials in heterogeneous populations demonstrated little if any evidence of such efficacy. Nine letters to the editor demonstrated a similar pattern. Conclusions. The large number of case series concerning gabapentin is striking. The number of reports and their distribution in many different journals created a type of "echo chamber" effect, through which the sheer number of publications and citations may give legitimacy to the practice of using gabapentin for bipolar disorder. Although the case series were generally of poor quality, their publication in peer-reviewed journals may have been partially responsible for the widespread use of an ineffective medication.