Abstract
BackgroundRecent analyses of antiepileptic drugs have indicated an increase in the risk of suicidality. The objective of this report was to provide clinical information and an independent meta-analysis of divalproex sodium and suicidality events by analyzing data from 13 placebo-controlled studies and 1 low-dose controlled study.MethodsAdverse events considered to be possibly suicide related were identified using the Columbia Classification Algorithm of Suicide Assessment (C-CASA) methodology. Indications included epilepsy, bipolar disorder, migraine prophylaxis, impulsive aggression, and dementia. Narratives were produced for every event, and suicidality event ratings were performed by a third party blinded to treatment assignment. Statistical analyses were conducted using methodology similar to that reported by the US Food and Drug Administration (FDA).ResultsSuicidality events were identified in 5 of the 13 placebo-controlled studies. Of the 1,327 (0.83%) subjects taking divalproex sodium, 11 had suicidality events: 2 suicide attempts and 9 suicidal ideation. Of 992 (0.91%) subjects taking placebo, 9 had suicidality events: 1 preparatory act toward suicide, 2 suicide attempts, and 6 suicidal ideation. Across placebo-controlled studies, the overall estimated odds ratio (OR) of suicidal behavior or ideation was 0.72 (95% CI 0.29 to 1.84). The OR for suicidal behavior was 0.37 (95% CI 0.04 to 2.58), and the OR for suicidal ideation was 0.90 (95% CI 0.31 to 2.79).ConclusionsIn this meta-analysis, divalproex sodium does not appear to increase the risk of suicide-related adverse events relative to placebo in the populations studied. Clinicians should nonetheless remain vigilant in assessing suicidality, not only in patients treated for mental disorders with inherently high suicide risk, but also in patients taking antiepileptic medications.
Highlights
Recent analyses of antiepileptic drugs have indicated an increase in the risk of suicidality
The study databases were searched for possibly suiciderelated adverse events (PSRAEs) that occurred during the double-blind phase of treatment, within 1 day of stopping randomized treatment, or on the first day of a protocol-specified tapering period
Of 2,319 subjects from placebo-controlled studies (n = 1,327 for Divalproex sodium (DVPX) and n = 992 for placebo), 6% participated in an epilepsy study, 71% in psychiatry studies, and 22% in migraine studies
Summary
Recent analyses of antiepileptic drugs have indicated an increase in the risk of suicidality. 6 years ago, the US Food and Drug Administration (FDA) evaluated the association between antidepressant agents and the increased risk of suicidality. This investigation was extended to the use of other medications including antiepileptic drugs (AEDs). In the case of antidepressants, the results of such analyses led to the addition of a warning to prescribing information regarding increased suicidality risk in the pediatric population. The FDA published their statistical review and evaluation of AEDs and suicidality in 2008 [4], which has led to prescribing information modifications [5]
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