Aarhus, Denmark—Three common forms of antiepileptic drugs are associated with an increased risk of suicide by patients, according to a new study, but the benefits of the medications appear to outweigh the risks.

In a study published in Annals of Neurology, researchers from Aarhus University and Aarhus University Hospital used the Danish National Prescription Register to identify all incident users of antiepileptic drugs aged 15 years or older in Denmark between July 1997 and December 2015.

They determined that, in 2017, 180,000 Danes received a prescription for antiepileptic drugs, which, in addition to being used for treatment of epilepsy, might also be prescribed for other conditions, such as bipolar disorder and migraine. The nested case–control study sought to define exposure to antiepileptic drugs at the time of suicide, with analysis of suicide risk associated with the nine most commonly used antiepileptic drugs.

Focusing on 1,759 patients who committed suicide, the study team determined that current versus previous use of any antiepileptic drug was associated with an increased risk of suicide (MRR, 1.26; 95% CI, 1.130-1.40).

Researches emphasize that the excess risk was observed in patients with a history of suicidal behavior (MRR, 1.28; 95% CI, 1.07-1.54) and in those without (MRR, 1.26; 95% CI, 1.11-1.43), as well as in individuals with a familial predisposition to psychiatric disorders (MRR,1.48; 95% CI, 1.18-1.87) and in those without (MRR, 1.21; 95% CI, 1.07-1.35).

Use of antiepileptic drugs was associated with an increased risk of suicide,” the authors conclude. “The findings do not support that the risk of suicide following treatment with antiepileptic drugs identified in randomized trials is explained by prior suicidality or familial predisposition to psychiatric disorders. The additional risk of suicide associated with use of antiepileptic drugs was generally low and should be balanced against benefits of treatment.”

The authors say that their results support an FDA warning in 2008 that suicidal thoughts and behavior might occur as side effects from the use of antiepileptic medicine.

“The study shows that people who are being treated with anti-epileptic drugs have a slightly increased risk of suicide. This applies to people who take the medicine for epilepsy, but also to those who take it for migraines or psychological disorders,” explained lead author Julie Werenberg Dreier, PhD.

Dr. Werenberg Dreier noted that the study identified 40 to 60 suicides per year recently among treated with antiepileptic drugs at the time they committed suicide. During the same period, there were approximately 600 people in total who committed suicide in Denmark each year.

The study identified the drugs phenobarbital, clonazepam, and pregabalin as being particularly associated with an increased risk of suicide.

In general, however, the researchers determined the extra risk of suicide is very low and must be balanced against the medication’s beneficial effects, including reducing and preventing seizures and related accidents and death.

“Therefore, our recommendation is that people undergoing treatment with anti-epileptic drugs are particularly aware and contact their doctor if they experience suicidal thoughts,” said coauthor Jakob Christensen, MD, PhD. “Suicide is a rare consequence of treatment with anti-epileptic drugs—but is of course also very serious. So this is why we should react so as to avoid as many cases as possible.” He recommended efforts to identify antiepileptic drugs with the lowest possible risk of suicidal behavior.
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