Reconsidering antiepileptic medications as a treatment for bipolar disorder

A study coming out in tomorrow’s edition of Archives of General Psychiatry may prompt doctors and patients to reconsider the merits of using antiepileptic drugs to treat people with bipolar disorder.

Just last year, the U.S. Food and Drug Administration issued an alert that antiepileptic drugs -- such as Neurontin (generic name gabapentin), Lyrica (pregabalin), Topamax (topiramate) and Tegretol (carbamazepine) -- increased the risk of suicidal thoughts and behaviors. That’s particularly important for patients with bipolar disorder, because they already have a higher risk of suicide compared to healthy people.

But the new analysis finds that bipolar people who took one of 11 antiepileptic medications had the same rate of suicide attempts -- 13 per 1,000 patients per year -- as those who didn’t take any drugs for their condition. That rate was slightly lower than for bipolar people who took lithium (18 suicide attempts per 1,000 patients per year). It was also much lower than the rate of suicide attempts among bipolar people in the year before they began taking antiepileptic medications (72 per 1,000 patients per year).

The findings are based on records of 47,918 patients with bipolar disorder who were included in the PharMetrics medical claims database. The study was conducted by researchers from the Center for Health Statistics at the University of Illinois at Chicago and the Columbia University College of Physicians and Surgeons in New York. Two of the researchers have produced expert testimony for Pfizer Pharmaceuticals in litigation involving Neurontin. Pfizer purchased the dataset from PharMetrics for $15,000 but was not involved in the research and didn’t influence or review the results, according to the researchers.

The work was funded by grants from the National Institute of Mental Health and the Agency for Healthcare Research and Quality.

You can read the FDA’s 2008 statistical review of antiepileptic drugs and suicidal ideation and behavior here. The most up-to-date info from the agency is online here.

-- Karen Kaplan

Photo: Perhaps this drug is safer, and more useful, than thought. Credit: Pfizer Inc.

Comments

[Mary H]

What are the other medications included in your list of 11 antiepilectic medications?

[Jack London]

I am personally familiar with this study and recommend in the strongest terms that anyone who reads it dig deeper. The FDA study was based on random controlled trials. Dr. Gibbons' et al study was based on a post hoc study of parsed claims records. Dr. Gibbons was paid vastly more by Pfizer lawyers as an expert witness in connection with his study of the FDA analysis and in connection with his statistical analysis of Neurontin, one of the drugs, which was marketed off-label to doctors for purposes not approved by the FDA, than was contributed by the NIH grant. The Gibbons study does not account for changes in the patients during the period of the study that are commonly associated with other drugs (which Dr. Gibbons did not include), with treatment, or with the passage of time. It does not actually study whether the patients actually took the drugs, the doses, or the duration.
One of the legal problems Neurontin had in 2004 when the Department of Justice brought charges for Warner-Lambert's improper marketing of Neurontin was that the drug had been promoted in the medical literature without reliable science.