Still more controversy over this group of medications. A new study suggests that patients with bipolar disorder who take these anti-epileptic drugs donot have an increased risk of committing suicide, despite FDA warnings to the contrary ( back story here).
Bipolar patients treated with antiepileptics attempted suicide at the same rate as patients who received no medication or lithium. The rate of suicide attempts was higher before patients began taking the meds than afterwards, according to the study in the Archives of General Psychiatry (see abstract). And compared with patients taking no drugs, those on a single antiepileptic had a reduced risk of suicide attempts.
The study, which analyzed records collected between 2000 and 2006 on 47,918 bipolar patients from the PharMetrics Patient Centric Database, a national claims database, was led by Robert Gibbons of the University of Illinois at Chicago, whose previous study on antidpressants and suicides was controversial. Two years ago, he published a study in the American Journal of Psychiatry blaming a 14 percent rise in teenage suicides - from 2003 to 2004 - on the widespread publicity given links between antidepressants and suicide (background here).
Why did the study differ from the findings of the FDA meta-analysis of randomized clinical trials? "There are several possibilities," the researchers wrote. "First, the FDA analysis was based on adverse event reports of suicidal thoughts and behavior, whereas our analysis is based exclusively on suicide attempts. Second, the FDA meta-analysis combined several indications including psychiatric, pain, and epilepsy. Note that the FDA's subanalysis for psychiatric indications was not significant. Third, most of the suicidality events in the FDA analyses were observed for only 2 of the 11 AEDs, lamotrigine and topiramate.
"Fourth, the results of the FDA analysis could be affected by 2 ascertainment biases. Patients treated with a drug will have more adverse effects than patients taking a placebo and, therefore, more opportunity to describe their suicidal thoughts.16 Suicide attempts by an overdose of study medication will result in contact with the health care system (eg, an emergency department), and therefore have a greater likelihood of being detected than an overdose while taking placebo."
In the latest study, the researchers wrote their analysis "reveals that there is a selection effect, in that the pre-treatment suicide attempt rate is five times higher than the rate in untreated patients. If pre-treatment suicide attempt rates reflect the severity of illness, it is the more severely impaired patients who receive treatment with an antiepileptic drug or lithium. Nevertheless, the post-treatment suicide attempt rate is significantly reduced relative to their elevated pre-treatment levels to the level found at or below patients not receiving treatment."
The study was funded by the National Institute of Mental Health and the Agency for Healthcare Research and Quality. Gibbons has served as an expert witness for the US Department of Justice, Wyeth, and Pfizer, regarding Neurontin, one of the drugs reviewed in the study. Other disclosures: John Mann received research support from GlaxoSmithKline and served as an adviser toi Lilly and Lundbeck Pharmaceuticals. C. Hendricks Brown directed a suicide prevention program at the University of South Florida that received funding from JDS Pharmaceuticals.