Cross-sensitivity of patient-perceived adverse cognitive effects with antiepileptic drug use

The extent to which adverse cognitive effects (ACEs) to a specific antiepileptic drug (AED) affect the chance of developing ACEs to other AEDs (i.e., cross-sensitivity) is unknown. We investigated the rates of cross-sensitivity of ACEs among AEDs and examined the association between clinical characteristics and occurrence of having ACEs to multiple AEDs in adults with epilepsy.

The rates of cross-sensitivity of intolerable ACEs (IACEs; i.e., ACEs leading to dosage reduction or discontinuation) and the non-AED predictors of IACEs were investigated in 2269 patients who had taken at least two AEDs at a single center. We accounted for AED load and looked for specific cross-sensitivities between AEDs as well as cross-sensitivity based on the AED mechanism of action.

Among the 2269 patients, the highest rates of IACEs were seen with TPM (26.3%), ZNS (9.8%), PHT (8.8%), and VPA (8.5%). Intolerable ACEs to two or more AEDs occurred in 100 patients (4.4%). History of psychiatric condition(s) and absence seizure type were independent predictors of IACEs to two or more AEDs. High rates of cross-sensitivity of IACEs were seen between phenytoin (PHT) and lamotrigine (LTG), valproate (VPA) and phenytoin, and valproate and zonisamide (ZNS). For example, of patients who had IACEs to VPA and were also prescribed ZNS, 46.2% had IACEs to ZNS (abbreviated as VPA→ZNS: 46.2%); of patients who had IACEs to ZNS and were also prescribed VPA, 37.5% had IACEs to VPA (abbreviated as ZNS→VPA: 37.5%). Other results are as follows: LTG→PHT: 28.6%, PHT→LTG: 20.0%, PHT→VPA: 42.9%, and VPA→PHT: 27.3%. No specific cross-sensitivities were found among AEDs sharing a similar mechanism of action.

The probability of ACE intolerability to an AED can increase if a patient developed ACE intolerability to another AED. The cross-sensitivity rates for ACE intolerability between LTG and PHT, PHT and VPA, and VPA and ZNS were found to be particularly high. The cross-sensitivity rates provided here may be clinically useful for predicting ACE intolerability in patients taking certain AEDs and for AED selection in individual patients.