FDA Warns of Suicide Risk With Antiepileptic Drugs

The FDA has issued an alert to health care professionals, warning that patients who take antiepileptic drugs (AEDs) have approximately double the risk of suicidal behavior or ideation compared with patients given placebo. The warning is based on an analysis of 199 placebo-controlled clinical trials of 11 AEDs.

The FDA’s comparison included 27,863 study participants who took AEDs and 16,069 who received a placebo. The studies included patients 5 and older who were being treated for epilepsy, psychiatric disorders (eg, bipolar disorder, depression, and anxiety), and other conditions such as migraine and neuropathic pain. Patients who received an AED had a 0.43% risk of suicidality, as there were 105 reports of suicidal thoughts and behaviors in the group, and four treated patients committed suicide. In the placebo group, there were 35 reports of suicidality, although no patients committed suicide; the risk of suicidal thoughts and behaviors was 0.22% in this group. The increased risk began as early as one week after starting AED treatment and continued to at least 24 weeks, noted the FDA.

Alice Hughes, MD, medical officer in the Division of Neurology Products at the FDA in Rockville, Maryland, told Neurology Reviews, “This analysis indicated that the increased risk of suicidal thoughts and behaviors is shared by all AEDs. The results were generally consistent among the 11 AEDs that were analyzed. The mechanism for the increase in the risk for suicidal thoughts and behavior observed in patients treated with AEDs is unknown.”

According to Dr. Hughes, completed suicide is a rare event in the limited time frame of clinical trials. Consequently, the primary outcome of the study was suicidal behavior and ideation (completed suicide, suicide attempt, preparatory acts toward an imminent suicide attempt, and suicidal ideation). Dr. Hughes noted significant differences in sample sizes between the treatment groups, but she asserted that this was accounted for by the statistical analysis.

With respect to patients who are taking AEDs, “physicians should balance the risk of suicidality with the clinical need for the drug for individual patients,” advised Dr. Hughes. She added, “The FDA expects that the details of our analyses will be presented and discussed at a future advisory committee meeting.”

NR