Background: A recent meta-analysis of randomized trials revealed that antiepileptic drugs (AEDs) as a class increase the risk of suicidal thoughts and behavior. We conducted an observational study with data from the United Kingdom General Practice Research Database to investigate if an increase in risk for different groups of AEDs is also evident in clinical practice.
Methods: This was a nested case-control study in a cohort of 44,300 patients with epilepsy who were treated with AEDs. Patients with self-harm or suicidal behavior were identified by predefined codes. We included 453 cases and 8,962 age-matched and sex-matched controls. AEDs were classified into 4 groups: barbiturates, conventional AEDs, and newer AEDs with low (lamotrigine, gabapentin, pregabalin, oxcarbazepine) or high (levetiracetam, tiagabine, topiramate, vigabatrin) potential of causing depression. Adjusted odds ratios (OR) were calculated using conditional logistic regression.
Results: Current use of newer AEDs with a high potential of causing depression was associated with a 3-fold increased risk of self-harm/suicidal behavior (OR = 3.08; 95% [CI] 1.22-7.77) as compared with no use of AEDs during the last year. Use of barbiturates (OR = 0.66; 95% CI 0.25-1.73), conventional AEDs (OR = 0.74; 95% CI 0.53-1.03), or low-risk newer AEDs (OR = 0.87; 95% CI 0.47-1.59) was not associated with an increased risk.
Conclusions: Newer AEDs with a rather high frequency of depressive symptoms in clinical trials may also increase the risk of self-harm or suicidal behavior in clinical practice. For the most commonly used other groups of AEDs, no increase in risk was observed.