Antiepileptic drugs associated with new onset of Parkinson's disease

A large UK biobank study reports increased rates of new Parkinson's disease after prescription of anticonvulsants.

Are certain antiepileptic drugs associated with increased risk of later Parkinson's disease?

A recent case-control study published in JAMA Neurology evaluated data from 1,433 people with a coded diagnosis of PD and 8,598 controls from the UK Biobank.1 Of the 1,433 PD patients, 61% were male and the mean age was 71 years.

The result: after adjustment for age, sex and socioeconomic disadvantage, prescription of anticonvulsants was associated with an increased incidence of PD (odds ratio 1.80; 95% CI 1.35-2.40). The trend emerged that a higher number of prescriptions and medication with multiple anticonvulsants were associated with a higher risk of PD.

The four most commonly prescribed antiepileptic drugs in the UK included in the analysis were carbamazepine, lamotrigine, levetiracetam and sodium valproate. Subgroup analyses revealed the highest odds of PD after valproate use (OR 3.82), followed by levetiracetam (OR 3.02), lamotrigine (OR 2.83) and lastly carbamazepine (OR 1.43). To exclude cases of transient drug-induced parkinsonism, which may resolve after drug discontinuation, antiepileptic prescriptions were excluded within 1, 2 and 5 years prior to the time of initial PD diagnosis, which did not change the associations, except for carbamazepine in the 1-year period.

Further studies needed for classification

Another case-control study of 1,055 people, also published in JAMA Neurology in 2022, had reported an association between epilepsy and Parkinson's disease. Up to ten years prior to a Parkinson's disease (PD) diagnosis, a wide range of symptoms stood out in primary care. In particular, the study documented temporal associations between epilepsy (OR 2.5) and hearing loss (OR 1.66) with later PD, which had not been previously reported in detail. These findings were subsequently replicated using data from the UK Biobank.2,3

To the best of our knowledge, the above work is the first to examine the role of the most common anticonvulsants in this context. Thus, neither relationship can be considered as established to date and the relative contribution of epilepsy versus antiepileptic drugs should be further explored.

"Although we are not aware of any prospective data confirming or refuting this observation, it is supported by post-mortem studies showing that individuals with drug-induced parkinsonism have lower levels of homovanillic acid and dopamine in the striatum," the authors noted.

A physician not involved in the study commented on the usefulness for future studies to evaluate the risk of Parkinson's after anticonvulsant use in non-epileptic patients with chronic pain or bipolar disorder.1 Gabapentin and pregabalin, which were not included in the above study, are commonly used as chronic analgesics, while carbamazepine and sodium valproate are often used as mood stabilisers.

  1. Belete, D. et al. Association Between Antiepileptic Drugs and Incident Parkinson Disease. JAMA Neurology 80, 183–187 (2023).
  2. Simonet, C. et al. Assessment of Risk Factors and Early Presentations of Parkinson Disease in Primary Care in a Diverse UK Population. JAMA Neurology 79, 359–369 (2022).
  3. Systematic Study Identifies Association Between Incident Parkinson Disease and Antiepileptic Drug Use. Neurology live (2023).

    Last accessed: 22 March 2023