Aggravation of epilepsy by anti‐epileptic drugs

Abstract

The possibility that so‐called anti‐epileptic drugs (AEDs) may aggravate epilepsy must always be borne in mind by the clinician. Many reports of such aggravation of seizures have been published. Most such reports are anecdotal and speculative, and suggest that many such reactions are idiosyncratic. However, for some there is a sufficient body of evidence to suggest that some AEDs used in certain epilepsies may consistently cause worsening of seizures. Seizure aggravation may include increase in the frequency or severity of existing seizures, emergence of new types of seizure, or the occurrence of status epilepticus. The pathophysiology of seizure aggravation is poorly understood including nonspecific effects such as those associated with sedation, druginduced encephalopathy, and paradoxical or inverse pharmacodynamic effects. For some epilepsies the choice of AEDs may be inappropriate, and although the mechanism of seizure aggravation is not clear, its occurrence may be fairly predictable. This is best documented for the use of carbamazepine in idiopathic generalized and myoclonic epilepsies. Most other AEDs have been reported occasionally to cause seizure aggravation. The lowest risk of seizure aggravation appears to be with valproate. Risk factors for worsening of seizures are epileptic encephalopathy, polytherapy, high frequency of seizures, and cognitive impairment. Advances in pharmacogenomics may in the future enable such adverse effects to be predicted for individual patients. Meanwhile, a systematic approach to reporting AED‐induced seizure aggravation should be developed.

Safety and Tolerability of Antiepileptic Drug Treatment in Children with Epilepsy

“…Seizure aggravation as a consequence of prescribing an inappropriate AED for the particular seizure type or because of a paradoxical exacerbation of seizures should be followed by prompt review of treatment [8][9][10][11][12][13][14][15][16][17][18] (table II). Once identified, the most appropriate AED, starting with low doses, slow titration, adequate posology choice and individualization of the minimal effective maintenance doses, may greatly improve safety and tolerability.…”

Lacosamide Reduces Seizure Severity but Increases Seizure Frequency in PTZ-Kindled Rats

“…At this high dose, an increase in seizure susceptibility was described earlier, drug-induced seizures being observed in 50% of the kindled rats treated with 30 mg/kg LCS [17]. Nevertheless, it is commonly accepted that all AEDs can aggravate epilepsy at high, supratherapeutic doses [18].…”

Diagnosis and management of the epilepsies in children

“…The pathophysiology of seizure aggravation is not fully understood; it involves non-specific effects such as sedation, drug-induced encephalopathy, and paradoxical or inverse pharmacodynamic effects. 17 …”