There is no evidence to support the suicidality warning for newer anti-epileptic drugs

Newer anti-epileptic drugs do not appear to increase the risk of suicidality in epilepsy patients without a history of suicidality, according to the results of a meta-analysis recently published in JAMA Neurology.

Most anti-seizure drugs carry a warning of increased risk of suicidality, as mandated by the US Food and Drug Administration, based on a meta-analysis of suicidality between drug-treated people versus placebo in randomized clinical trials Studies conducted before 2008 were compared, ”the authors explained.

Although they were not examined similarly, anti-epileptic drugs approved after the meta-analysis was published had to carry the suicidality class warning. This meta-analysis aimed to review phase 2 and 3 placebo-controlled studies that compared the suicide risk of anti-epileptic drugs approved after 2008 with placebo.

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The main endpoints of the study were suicidality (total and thought), attempted suicide, and accomplished suicides. The meta-analysis compared the risk of each endpoint for the drugs as a group and for individual drugs versus placebo.

The analysis included 5 anti-epileptic drugs (eslicarbazepine, perampanel, brivaracetam, cannabidiol and cenobamate) that were evaluated in 17 randomized clinical trials. Of the total of 5,996 patients, 4,000 received anti-seizure medication and in 1996 a placebo.

“There was no evidence of an increased risk of suicidal ideation (drug 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) total or for one person drug, ”reported the authors. The results showed that 12 patients (0.3%) treated with anti-epileptic drugs and 7 patients (0.35%) treated with placebo (P = 0.74) had thoughts of suicide.

The data analysis also found that 3 patients who received anti-epileptic drugs had attempted suicide versus 0 patients who received placebo (P = 0.22). No completed suicides were reported.

“In summary, our study shows that in patients with epilepsy without a history of suicidality, there is no evidence that any of the 5 recently admitted patients” [antiseizure medications] Prospectively assessed using FDA guidelines on suicidality assessment increase the risk of suicidality, ”the authors concluded. “The determination and labeling of the risk of suicidality should be based on evidence from randomized clinical trials and individualized for each new one [antiseizure medication]. “

Disclosure: Some study authors stated links with biotech, pharmaceutical, and / or device companies. For a full list of the author’s disclosures, see the original reference.


P. Klein, O. Devinsky, J. French et al. Suicidality Risk of Newer Antiepileptic Drugs: A Meta-Analysis. JAMA neurology. Published online August 2, 2021. doi: 10.1001 / jamaneurol.2021.2480

This article originally appeared on MPR

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