Antiepileptic Drugs and Suicide Attempts in Patients With Bipolar Disorder—Reply

Abstract

Mentari et al1 from the US Food and Drug Administration (FDA) raise questions and concerns regarding the conclusions of our recent article2 on the relationship between antiepileptic drugs (AEDs) and suicide attempts. In contrast to the FDA meta-analysis of randomized controlled trials of AEDs, which showed significantly increased risk of suicidal events (ideation and behavior) relative to placebo, we found no evidence of increased risk of AED treatment and suicide attempts in an observational cohort study of 47 918 patients with bipolar disorder. Our analysis compared periods of risk before and after treatment initiation (following diagnosis) and between individuals who were and were not treated with an AED. Our analysis adjusted for prior suicide attempts (in the year prior to diagnosis), concomitant treatment with other AEDs, lithium, antidepressants, and antipsychotics and age, sex, and year (2000–2006). All patients in our cohort had at least 1 year of continuous observation before and after their index bipolar disorder diagnosis. Results of our analysis indicated that rates of suicide attempts significantly decreased following treatment initiation and that overall there were no significant differences between patients who did or did not receive AED treatment. In a subgroup of patients who did not receive concomitant other AED, lithium, antidepressant, or antipsychotic treatment, AED treatment was associated with a significant decrease in suicide attempt rates (3 in 1000 patient-years vs 15 in 1000 patient-years; event rate ratio, 0.19; 95% confidence interval [CI], 0.08–0.47; P<.001). A series of sensitivity analyses that used advanced matching strategies and person-time monthly exposure analyses confirmed the overall results.