Newer AEDs linked to self-harm, suicidal behavior

Patients taking newer antiepileptic drugs (AEDs) that are associated with a high risk of depression may have an elevated risk of self-harm or suicidal behavior, but other groups of AEDs do not appear to carry the same risk, according to research published in the July 27 issue of Neurology, as reported in HealthDay News.

Frank Andersohn, MD, of the Charité-University Medical Center in Berlin, and colleagues analyzed data from patients with epilepsy who were treated with AEDs. The researchers compared 453 cases of self-harm or suicidal behavior with 8,962 controls, and classified AEDs into barbiturates, conventional AEDs, and newer AEDs with low potential to cause depression-lamotrigine (Lamictal, GlaxoSmithKline); gabapentin (Neurontin, Pfizer); pregabalin (Lyrica, Pfizer); and oxcarbazepine (Trileptal, Novartis)-or high potential to cause depression-levetiracetam (Keppra, UCB); tiagabine (Gabitril, Cephalon); topiramate (Topomax, Ortho-McNeil Neurologics); and vigabatrin (Sabril, Lundbeck).

Dr Andersohn told Formulary an earlier analysis conducted by FDA revealed an increased risk of suicidal thought and behavior for antiepileptic individuals as a group. But the analysis “lumped together” antiepileptic individuals, and it was impossible to identify meaningful differences between different antiepileptic medications.

“In contrast, our study indicates that some, but not all antiepileptic drugs may increase the risk of self harm and suicidal behavior in patients with epilepsy,” he said. “Especially the conventional drugs that were already several years on the market were not associated with an increased risk.”

He said additional, larger studies are needed to confirm the results his team’s research and to be able to investigate more rarely used antiepileptic drugs.

The researchers found that current use of newer AEDs with high potential to cause depression was linked to a higher risk of self-harm or suicidal behavior (OR, 3.08) compared with the absence of AED use in the previous year. Barbiturates, conventional AEDs, or the low-risk, newer AEDs were not found to be associated with a higher risk of self-harm or suicidal behavior.

“For a large part of the study period, the high-risk AEDs were licensed in the United Kingdom only as add-on for partial epilepsy, suggesting that the exposed patients were receiving these drugs as part of polytherapy regimens,” the authors wrote in an accompanying editorial. “Therefore, these patients possibly had drug-refractory epilepsy, a group that is at the upper end of the suicide-risk spectrum. Finally, a detailed clinical description of the epilepsy type and psychiatric comorbidity is lacking.”

Bayer Schering Pharma provided funding for database acquisition. One author disclosed financial ties to Bayer Schering Pharma and Novartis, and another disclosed ties to Sanofi-Aventis.