Antiepileptic Drugs Not Linked to an Increased Risk of Dementia

February 21, 2019

AED use was not significantly associated with dementia risk in patients followed by general practitioners and neuropsychiatrists, however, the potential harmful effects of levetiracetam generic brands on cognition should be further investigated.

Karel Kostev, PhD

According to the results of a recent real-world study, use of antiepileptic drugs (AED) was not significantly associated with an increased risk of dementia, however, the potential harmful effects of levetiracetam generic brands on cognition need additional investigation.

Researchers investigated the hypothetical association between AED use and dementia risk in 101,150 individuals receiving treatment from more than 1400 general practitioners and neuropsychiatrists in Germany between 2013 and 2017.

“The main takeaway is that, although the epilepsy is a significant risk factor for the subsequent development of dementia, antiepileptic drug use is not significantly associated with an increased dementia risk,” Karel Kostev, PhD, scientific principal, IQVIA Epidemiology Team, told NeurologyLive.

The retrospective cohort utilized data from the Disease Analyzer database (IQVIA), which complied drug prescriptions, diagnoses, and basic medical and demographic data obtained in anonymous format from computer systems used by general practitioners and specialists.

The study population included patients 60 years of age or older who received a first dementia diagnosis (n = 50,575) from one of the 1203 general practitioners or 202 neuropsychiatrists. Controls without dementia (n = 50,575) were matched (1:1) to dementia patients by age, gender, physician, diagnosis of mild cognitive impairment, and observation time prior to index date in years, which was a randomly selected visit between January 2013 and December 2017. The mean age was 81 years, and 61.5% of the study participants were women. The most frequent comorbidity was hypertension (73.3% in patients with dementia and 68.3% in controls), and the most commonly co-prescribed drugs were antidepressants (32.1% and 24.1%, respectively).

The main outcome of the study was the risk of dementia as a function of AED use. AEDs in the study included levetiracetam, valproate, clonazepam, topiramate, carbamazepine, lamotrigine, gabapentin, pregabalin, primidone, and others.

There was no significant association between any use of AEDs and dementia risk (OR = .99). The duration of AED therapy was also not associated with a risk of dementia (OR = 1.00 per therapy year).

The researchers found that the only group of drugs associated with an increased dementia risk were generic levetiracetam brands (OR = 1.70, P <.001), however, no association was found for the original levetiracetam brand (OR = .84, P >.05). The authors explained that additional research should be conducted to validate these results.

“Although there was no significant AED use dementia risk relationship in our study, levetiracetam generic drugs were found to be associated with an increased dementia risk,” Kostev explained. “This finding might be explained by differences in active pharmaceutical compounds but also by differences in excipients between branded and generic antiepileptic molecules. The potential deleterious effects of generic brands compared to original brands on cognition, but also other outcomes deserve further investigation. In another study, we published in Neurology one year ago, we could see that individuals with epilepsy with seizures had switched more frequently from branded to generic molecules than those without seizures.”

Additionally, the researchers demonstrated that epilepsy was a significant risk factor for the subsequent development of dementia.

While the strengths of the study included the use of real-world data, the high number of cases and controls, the number of comorbidities and co-prescribed drugs included, the study was subject to several limitations, however, such as the lack of data available from special epilepsy centers or on epilepsy severity and the potential misdiagnosis of dementia.

REFERENCE

Jacob L, Bohlken J, Kostev K. Is There an Association Between Antiepileptic Drug Use and Dementia Risk? A Case-Control Study. Journal of Alzheimer's Disease. 2018;1-7.

doi

: 10.3233/JAD-181194.