Evidence to Support Suicidality Warning for Newer Antiseizure Meds Lacking

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The analysis included 5 antiseizure medications (eslicarbazepine, perampanel, brivaracetam, cannabidiol, and cenobamate) evaluated in 17 randomized clinical trials.

Newer antiseizure medications do not appear to increase suicidality risk among epilepsy patients without a history of suicidality, according to the findings of a meta-analysis recently published in JAMA Neurology.

“Most antiseizure medications carry a US Food and Drug Administration-mandated class label warning of increased suicidality risk, based on a meta-analysis comparing suicidality between individuals treated with medications vs placebo in randomized clinical trials done before 2008,” the authors stated.

Despite not being studied similarly, antiseizure drugs approved after the publication of the meta-analysis were required to carry the suicidality class warning. This meta-analysis aimed to review placebo-controlled phase 2 and 3 studies comparing the risk of suicidality of antiseizure medications approved after 2008 to placebo.

The main endpoints of the study included suicidality (total and by ideation), suicide attempts, and completed suicides. The meta-analysis compared the risk of each outcome for the medications as a group as well as for individual medications vs placebo.

The analysis included 5 antiseizure medications (eslicarbazepine, perampanel, brivaracetam, cannabidiol, and cenobamate) evaluated in 17 randomized clinical trials. Of the total 5996 patients, 4000 received antiseizure medications and 1996 received placebo.

“There was no evidence of increased risk of suicidal ideation (drugs vs placebo overall risk ratio, 0.75; 95% CI, 0.35-1.60) or attempt (risk ratio, 0.75; 95% CI, 0.30-1.87) overall or for any individual drug,” the authors reported. Findings showed that suicidal ideation occurred in 12 patients (0.3%) treated with antiseizure medications and 7 patients (0.35%) treated with placebo (P =.74).

Data analysis also revealed that 3 patients receiving antiseizure medications attempted suicide vs 0 patients who received placebo (P =.22). No completed suicides were reported.

“In conclusion, our study shows that in patients with epilepsy without a history of suicidality, there is no evidence that any of the 5 recently approved [antiseizure medications] prospectively evaluated using FDA suicidality evaluation guidelines increase the risk of suicidality,” the authors concluded. “Determination and labeling of suicidality risk should be based on evidence from randomized clinical trials and individualized for each new [antiseizure medication].”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Klein P, Devinsky O, French J, et al. Suicidality risk of newer antiseizure medications: A meta-analysis. JAMA Neurology. Published online August 2, 2021. doi:10.1001/jamaneurol.2021.2480

This article originally appeared on MPR