Antipsychotics and seizures: higher risk with atypicals?

Almost all antipsychotics have been associated with a risk of epileptic seizure provocation. Among the first-generation antipsychotics (FGA) chlorpromazine appears to be associated with the greatest risk of seizures among the second-generation antipsychotics (SGA) clozapine is thought to be most likely to cause convulsions. This information is largely based on studies that are not sufficiently controlled. Besides, information about the seizure risk associated with newer antipsychotics is scarce.

The Pharmacovigilance Unit of the Basque Country (network of centers of the Spanish Pharmacovigilance System, SEFV) provided reporting data for adverse reactions (AR) from the whole SEFV to estimate the reporting odds ratio (ROR) for antipsychotics and seizures ("convulsions" as Single MedDra Query). Data was obtained from SEFV database from 1984 to the June 2011.

The total number of convulsions reported for SGA was 169 (total reported AR 3.204). The number of convulsions reported for FGA was 35 (total reported AR 2.051). 94 convulsions were reported in association with clozapine (total AR 1.052). The ROR for SGA versus FGA was 3.2 (CI 95%: 2.21-4.63). The ROR for SGA excluding clozapine versus FGA was 2.08 (CI 95%: 1.39-3.12).

Our results show that SGA may pose a higher risk of seizures than FGA, mainly, but not only due to clozapine. This is line with recent studies suggesting that some SGA carried a higher average risk of electroencephalographic abnormalities than many FGA. Nonetheless, It is well known that spontaneous reports do not allow strong inferences about adverse drug effects, because differences in reporting fractions by time, drug or type of event are difficult or even impossible to distinguish from differences in the occurrence rates of adverse events. Still, we consider that the possibility of SGA carrying a higher risk of seizure induction than FGA warrants further research.