In this month’s issue of the journal Brain a new study investigates whether the drugs prescribed to control seizures can increase the risk of psychotic symptoms in some people. After reviewing over ten years of medical records of patients treated for epilepsy, the researchers concluded that up to one in seven cases of patients with epilepsy who were later diagnosed with psychosis could be attributed to an adverse effect of the anti-epileptic drugs.
“Antiepileptic drug-induced psychotic disorder (AIPD) was common among epilepsy patients who develop psychotic symptoms,” the researchers write. “In our study one in seven patients with epilepsy who presented with psychosis had AIPD.”
It is well established that patients who have epilepsy are at an increased risk for psychiatric symptoms including psychosis. Past research has also demonstrated that the drugs used to treat epilepsy (antiepileptics) can also increase the risk for these symptoms. What is less well understood is what percentage of epileptic patients develop psychiatric symptoms as a result of their medication and how psychiatrists can learn to better recognize antiepileptic-induced psychotic disorder (AIPD).
Hampering efforts to understand the signs of AIPD is the general controversy and disagreement in the field over how precisely to define psychotic ‘disorders’ more broadly, and the lack of a reliable and valid diagnostic system.
“As a result of these limitations in knowledge, the management of AIPD in clinical practice is extremely challenging and not evidence-based,” write the study authors, led by Ziyi Chen, from the University of Melbourne.
“Misdiagnosing AIPD as primary psychotic disorder may lead to inappropriate management, including continuation of the culprit AED and additional treatment with antipsychotic drugs. Often, the psychotic symptoms of AIPD persist in a fluctuating manner as long as the AED is continued. The patient may endure both the adverse effects of the AED and potential exacerbation of epilepsy by antipsychotic drug therapy.”
This latest study attempted to bring some clarity to this issue by investigating the case reports of patients with epilepsy who developed psychosis and comparing those who took antiepileptic drugs and those who did not. The researchers reviewed the records of 2,630 patients who were treated between 1993 and 2015 at the Royal Melbourne Hospital in Australia.
The study found that 5.6% of all patients with epilepsy developed AIPD and that one in seven patients with epilepsy who experience psychosis are experiencing an adverse reaction to their seizure medication. In this study, females appeared to be at a higher risk than males for AIPD, with almost 2/3 of all AIPD cases being women. Also, those with specifically temporal lobe epilepsy appeared to be at a higher risk.
Certain antiepileptic drugs carried an increased risk for AIPD. According to the study, the drug levetiracetam (Keppra, Elepsia) was most commonly associated with AIPD, leading the researchers to warn that “when a patient with epilepsy presents with psychotic symptoms current usage of levetiracetam should raise the strong suspicion of AIPD.” Meanwhile, the drug carbamazepine was negatively associated with AIPD, suggesting it “might be a safe substitution for the offending agent.”
While patients with AIPD did not have more hallucinations or delusions than epileptic patients experiencing psychosis who did not take antiepileptics, those with AIPD did show more disorganized thinking and abnormal behaviors.
Interestingly, the study data did not indicate that AIPD was more common when higher doses of the drugs were used or when patients had been more rapidly tapered off of a drug. The researchers suggest that individual differences in the metabolism of the antiepileptic drugs may play a role in the increased risk for AIPD.
Chen, Z., Lusicic, A., O’Brien, T.J., Velakoulis, D., Adams, S.J. and Kwan, P., 2016. Psychotic disorders induced by antiepileptic drugs in people with epilepsy. Brain, p.aww196. (Abstract)