Considerations for Physicians

Data from 199 placebo-controlled clinical studies covering eleven different antiepileptic drugs were reviewed and analyzed for reports of suicidal behavior (completed suicides, suicide attempts and preparatory acts) and suicidal ideation. The studies examined the effectiveness of the drugs in epilepsy, psychiatric disorders (e.g., bipolar disorder, depression and anxiety) and other conditions (e.g., migraine and neuropathic pain syndromes). The analysis included a total of 43,892 patients ages five and older (27,863 in drug treatment groups and 16,029 in placebo groups). There was a statistically significant increased risk of suicidal behavior and suicidal ideation in the patients randomized to receive an antiepileptic drug compared to patients who received a placebo. The estimated overall risk was about twice that of the placebo group. There were an estimated 2.1 per 1000 (95% CI: 0.7, 4.2) more patients in the drug treatment groups who experienced suicidal behavior or ideation than in the placebo groups. Four of the patients who were taking one of the antiepileptic drugs committed suicide, whereas none of the patients in the placebo group did. The increased risk of suicidal behavior and suicidal ideation was observed at one week after starting the drug and continued to at least 24 weeks. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be reliably assessed. FDA will be working with manufacturers of marketed antiepileptic drugs to include this new information in the labeling for these products. FDA is also planning to discuss these data at an upcoming advisory committee meeting. All patients treated with antiepileptic drugs should be monitored for suicidality and other unusual changes in behavior. Symptoms such as anxiety, agitation, hostility, mania and hypomania may be precursors to emerging suicidality.