COMMENTARY

Antiepileptics and Suicide: Examining the Risk Across Indications

Laurie Barclay, MD

Disclosures

August 24, 2010

Suicide-Related Events in Patients Treated With Antiepileptic Drugs

Arana A, Wentworth CE, Ayuso-Mateos JL, Arellano FM
N Engl J Med. 2010;363:542-551

Summary

Based on a meta-analysis of clinical trial data, use of antiepileptic drugs has previously been linked to suicidal ideation and/or behavior. Using observational data collected during clinical care of 5,130,795 patients representative of the general UK population, this study looked at the association between the use or nonuse of antiepileptic drugs and suicide-related events, which were defined as attempted or completed suicides in patients with epilepsy, depression, or bipolar disorder.

The rate of suicide-related events per 100,000 person-years was 15.0 (95% confidence interval [CI], 14.6-15.5) in patients without epilepsy, depression, bipolar disorder, or antiepileptic drug treatment, compared with 38.2 (95% CI, 26.3-53.7) in patients with epilepsy who did not receive antiepileptic drugs, and 48.2 (95% CI, 39.4-58.5) in patients with epilepsy who received antiepileptic drugs.

Adjustment using logistic regression analysis showed that the use of antiepileptic drugs was not associated with an increased risk for suicide-related events among patients with epilepsy (odds ratio [OR], 0.59; 95% CI, 0.35-0.98) or bipolar disorder (OR, 1.13; 95% CI, 0.35-3.61). However, the use of antiepileptic drugs was associated with a significantly increased risk for suicide-related events in patients with depression (OR, 1.65; 95% CI, 1.24-2.19), as well as in patients without epilepsy, depression, or bipolar disorder (OR, 2.57; 95% CI, 1.78-3.71).

Viewpoint

Limitations of this study include use of observational data with possible confounding, and wide confidence intervals for several findings. In addition, patients with a history of suicide-related events were excluded from the analysis, which may limit generalizability. Nonetheless, current use of antiepileptic drugs was not associated with heightened risk for suicide-related events in patients with epilepsy, but risk of these events was increased in patients with depression and in those who received antiepileptic drugs for indications other than epilepsy, depression, or bipolar disorder.

Patients in the latter group may have been treated with antiepileptic drugs for pain-related conditions, such as herpes zoster. The study design does not allow determination of whether antiepileptic drugs per se contributed to suicidality in these patients, but chronic pain itself has been associated with an increased risk for suicide, and use of antiepileptic drugs in these patients could be a marker of depression linked to chronic pain.

These results do not confirm previous US Food and Drug Administration (FDA) findings in a meta-analysis of data from placebo-controlled clinical trials, which suggested that antiepileptic drugs used in a range of indications for up to 24 weeks are linked to suicidality. However, most of the suicide-related events in the FDA meta-analysis were not attempted or completed suicides, which were the endpoints used in the present study.

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