Persons with Alzheimer’s disease use antiepileptic drugs more often than persons without Alzheimer’s disease, as it was indicated in the doctoral thesis of Tatyana Sarycheva. Use of antiepileptic drugs increased considerably around the time when Alzheimer’s disease was diagnosed. The thesis also found that antiepileptic drug use is associated with the increased relative risk of stroke and death among persons with Alzheimer’s disease. The public examination of the doctoral thesis will be held online on 15 June 2020 starting at 10 AM.
The results are based on the nationwide MEDALZ dataset. Previous studies on antiepileptic drug use in persons with Alzheimer’s disease are limited and the risks of stroke and mortality among antiepileptic drug users with Alzheimer’s disease were not investigated previously.
Persons with Alzheimer’s disease are more susceptible to the risk of adverse events of antiepileptic drugs
The use of antiepileptic drugs was associated with 37 per cent increased relative risk of stroke. The thesis also found that among persons with Alzheimer’s disease, risk of mortality was increased by 23 per cent in association with antiepileptic drug use. The risks of stroke and mortality were particularly elevated for the first three months of antiepileptic drug use, and remained after accounting for several chronic diseases, socioeconomic position and use of concomitant medications. Certain antiepileptic drugs are known to be involved in drug-drug interactions and have pro-arrhythmic mechanisms. However, further research is needed to study possible mechanisms explaining these novel results.
Risk of major adverse events is associated with the type of antiepileptic drugs
Users of newer or older antiepileptic drugs did not differ in risk of stroke. However, compared to users of newer antiepileptic drugs, users of older antiepileptic drugs had a 79 per cent increased relative risk of mortality. The difference in the mortality risk may be explained by different indications of older versus newer antiepileptic drugs.
Incidence and prevalence of antiepileptic drug use increase around the time of Alzheimer’s disease diagnosis
The proportion of persons using antiepileptic drugs was greater among persons with Alzheimer’s disease than in persons without Alzheimer’s disease. The increase in the incidence and prevalence of antiepileptic drug use was more pronounced around the time of Alzheimer’s disease. During this period the number of new epilepsy diagnoses also raised but with the lower frequency and did not explain the increased incidence of antiepileptic drug use in persons with Alzheimer’s disease. It might be that antiepileptic drugs are used to treat neuropathic pain and behavioural and psychological symptoms of dementia, although the latter are not official indications for these drugs. Use of newer antiepileptic drugs was more common in persons with and without Alzheimer’s disease. However, persons with Alzheimer’s disease used older antiepileptic drugs more frequently than persons without Alzheimer’s disease.
The indications of antiepileptic drug prescriptions should be studied
Up to 1% of population needs chronic antiepileptic treatment to control epilepsy, and neuropathic pain is also a valid use indication. However, as persons with Alzheimer’s disease are particularly susceptible to adverse events, the use of antiepileptic drugs for other indications should be carefully considered in this vulnerable population. Alzheimer’s disease is among leading causes of death and disability and the number of people with Alzheimer’s disease is increasing around world.
The doctoral dissertation is a part of a nationwide register-based Medication use and Alzheimer’s disease (MEDALZ) cohort study. MEDALZ includes community-dwelling persons with clinically verified diagnoses of Alzheimer’s disease in Finland during 2005-2011 (N=70718) and a matched comparison cohort without Alzheimer’s disease. Data on antiepileptic use were extracted from the Finnish Prescription Register.
The doctoral dissertation of Tatyana Sarycheva, MD, MSc, entitled Prevalence, incidence and safety of antiepileptic drug use in persons with Alzheimer’s disease will be examined at the Faculty of Health Science. The opponent in the public examination will be Doctor Jenni Ilomaki of the Monash University, and the Custos will be Professor Anna-Maija Tolppanen from the University of Eastern Finland.
