No evidence of increased suicidality with normal use of anti-epileptic drugs

Although the US Food and Drug Administration (FDA) has issued warnings of an increased risk of suicidality for many anti-epileptic drugs, a recent meta-analysis suggests that there is currently no evidence that eslicarbazepine, perampanel, brivaracetam, cannabidiol and cenobamate pose a risk of suicidality increase in patients with epilepsy. The results of this study were published in JAMA Neurology.

In 2008, the FDA issued a warning about anti-epileptic drugs. The agency said these drugs may lead to an increased risk of suicidality, which includes suicidal thoughts and behavior. The warning came after analysis data from around 200 studies of 11 anti-epileptic drugs found that those drugs were associated with an increased risk of suicide compared to their placebo counterparts.

Researchers now believe the time to reconsider FDA-mandated suicidality warnings as epilepsy practice and new anti-epileptic drug development have been impacted.

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The recently carried out meta-analysis comprised 17 randomized controlled trials of phase 2 and 3 in which antiepileptic drugs were investigated in epilepsy. All studies looked at drugs approved since 2008, and each study had to report suicidality and / or suicidal ideation in order to be included in the meta-analysis.

The analysis included a pooled cohort of 4,000 patients who were assigned to an anti-epileptic drug and a placebo in 1996. Anti-epileptic drugs included in the analysis were eslicarbazepine, perampanel, brivaracetam, cannabidiol, and cenobamate.

Approximately 0.30% (n = 12) of the pooled cohort treated with an anti-epileptic drug had suicidal ideation versus 0.35% (n = 7) of those given a placebo (χ2 = 0.108; P = 0, 74). With regard to suicide attempts, there was no difference between the number of patients who received active therapy and those who received placebo (χ2 = 1.498; P = 0.22). No completed suicides were reported.

The meta-analysis showed no significantly increased risk of suicidal ideation (overall risk ratio [RR], 0.75; 95% CI 0.35-1.60 or suicide attempt (RR 0.75; 95% CI 0.30-1.87) with anti-epileptic drugs vs. placebo. When comparing individual drugs with placebo, the RR for suicidal ideation were 0.88 for brivaracetam, 1.22 for cenobamate, 0.76 for eslicarbazepine and 0.47 for perampanel.

No suicidality was reported with cannabidiol. There were a greater number of reports of suicidal ideation in patients receiving placebo (n = 4) compared to patients receiving perampanel (n = 3), but this was not statistically significant (χ2 = 2.063; P = 0 , 15).

Studies in this meta-analysis conducted prior to 2011 included non-standardized questionnaires on suicidality, which the researchers believe may have limited the “accurate risk assessment” for these drugs in the meta-analysis.

The researchers add that, based on the current level of evidence, “the FDA’s prescribed suicidality class warning for these drugs is not warranted,” but “the determination and labeling of suicidality risk should be based on evidence from randomized clinical trials and customized for each individual will”. new “anti-epileptic.

Disclosure: Several authors stated links to the pharmaceutical industry. For a full list of the details, see the original article.


P. Klein, O. Devinsky, J. French et al. Suicidality Risk of Newer Antiepileptic Drugs: A Meta-Analysis. JAMA Neurol. Published online August 2, 2021. doi: 10.1001 / jamaneurol.2021.2480 U.S. Department of Health. Statistical review and evaluation: anti-epileptic drugs and suicidality. Published May 23, 2008. Accessed September 9, 2021.

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