Determinants of health-related quality of life in pharmacoresistant epilepsy: Results from a large multicenter study of consecutively enrolled patients using validated quantitative assessments

Purpose: To evaluate the relative contribution of demographic and epilepsy-related variables, depressive symptoms, and adverse effects (AEs) of antiepileptic drugs (AEDs) to health-related quality of life (HRQOL) in adults with pharmacoresistant epilepsy. Methods: Individuals with epilepsy whose seizures failed to respond to at least one AED were enrolled consecutively at 11 tertiary referral centers. HRQOL was assessed by the Quality of Life in Epilepsy Inventory-31 (QOLIE31), AEs by the Adverse Event Profile (AEP), and depressive symptoms by the Beck Depression InventoryII (BDI-II). Multivariate linear regression models were used to identify variables associated with QOLIE-31 total score and subscale scores. Key Findings: Of 933 enrolled individuals aged 16 years or older, 809 (87%) were able to complete the selfassessment instruments and were included in the analysis. Overall, 61% of the variance in QOLIE-31 scores was explained by the final model. The strongest predictors of HRQOL were AEP total scores (beta = -0.451, p < 0.001) and BDI-II scores (beta = -0.398, p < 0.001). These factors were also the strongest predictors of scores in each of the seven QOLIE-31 subscales. Other predictors of HRQOL were age (beta = -0.060, p = 0.008), lack of a driving license (beta = -0.053, p = 0.018), pharmacoresistance grade, with higher HRQOL in individuals who had failed only one AED (b = 0.066, p = 0.004), and location of the enrolling center. Epilepsy-related variables (seizure frequency, occurrence of tonic-clonic seizures, age of epilepsy onset, disease duration) and number of AEDs had no significant predictive value on HRQOL. The AEP total score was the strongest negative predictor of HRQOL in the subgroup of 362 patients without depressive symptoms (BDI-II score < 10), but even in this subgroup the BDI-II score was retained as a significant predictor. Significance: In individuals with pharmacoresistant epilepsy, AEs of medication and depressive symptoms are far more important determinants of HRQOL than seizures themselves. When seizure freedom cannot be achieved, addressing depressive comorbidity and reducing the burden of AED toxicity is likely to be far more beneficial than interventions aimed at reducing the frequency of seizures.