Seizure aggravation by antiepileptic drugs

Abstract

Seizure aggravation by antiepileptic drugs (AEDs) is an overestimated phenomenon. While it undoubtedly occurs, the quality of evidence in most published reports is poor. Although seizure aggravation can be examined in clinical trials in the same way as seizure improvement, this is rarely done. Before concluding that an increase in seizures after the introduction of a new drug represents pharmacodynamic aggravation, alternative explanations should be explored. These include spontaneous fluctuation of seizure frequency, the presence of known seizure aggravators (such as sleep deprivation, alcohol, and psychotropic medications), progression of epilepsy, the development of drug resistance, and replacement of a partially effective drug with a less effective drug. The risk of incorrectly blaming a drug for a deterioration in seizures can be minimized by establishing baseline seizure frequency over a period long enough to encompass the extremes of seizure fluctuation and by educating the patient that a temporal relationship may not be a causal relationship. When feasible, the patient should continue the drug long enough to establish if the deterioration is transient. If the drug is stopped, rechallenge should be considered. The risk of seizure aggravation can be minimized by accurate diagnosis of the epilepsy syndrome and appropriate choice of AED.

Treatment changes in a cohort of people with apparently drug-resistant epilepsy: an extended follow-up

“…It is, however, likely that often an apparent deterioration in seizure control is due to coincidental change in seizure pattern when starting an ineffective drug,16 rather than a true antiepileptic drug-induced deterioration of seizure control. Seizure aggravation can deter people from considering further antiepileptic drug trials, making the prospect of improving seizure control more remote.…”

Case Files of the University of California San Francisco Medical Toxicology Fellowship: Lamotrigine Toxicity

“…This is a well-recognized complication, although the mechanism is poorly understood. There is very little experimental evidence and most theories are speculative and unproven [8]. One theory is that the anticonvulsant in high concentrations may have a depressant effect on inhibitory interneurons resulting in disinhibition of excitatory neurons and facilitation of epileptic discharges [9].…”

“…Carbamazapine remains the most commonly cited anticonvulsant to cause seizures in overdose, with one case series suggesting that the 10,11-epoxide may be responsible [10]. Another suggested mechanism is that some seizures are precipitated by drowsiness and the sedation produced by anticonvulsant overdose may encourage those susceptible seizure disorders [8].…”

Pharmacology of Antiepileptic Drugs in Clinical Practice

“…28 One of the best examples is AEDs acting selectively through potentiation of GABAergic activity. A few clinical studies support that AEDs may induce worsening of epilepsy by aggravating preexisting seizures, by triggering new seizures types, or by both mechanisms.…”