Consequences of antiepileptic drug withdrawal: A randomized, double-blind study (Akershus Study)

Objective: Despite side effects associated with the use of antiepileptic drugs (AEDs), withdrawal of AEDs remains controversial, even after prolonged seizure freedom. The main objective of this study was to assess the effects of AED withdrawal on cognitive functions, seizure relapse, health-related quality of life (HRQOL), and EEG results. Additionally, potential predictors for freedom from seizures after AED withdrawal were studied. Methods: Patients, seizure-free for more than 2 years on AED monotherapy, were recruited for a controlled, prospective, randomized, double-blinded withdrawal study lasting for 12 months, or until seizure relapse. Patients were randomized to AED withdrawal (n = 79) and nonwithdrawal (n = 81) groups. The examination program included clinical neurological examinations, neuropsychological testing, EEG-recordings, cerebral MRI, and assessments of HRQOL. Follow-up data on seizure relapse were also collected beyond the 12-month study period (median 47 months). Results: Seizure relapse at 12 months occurred in 15% of the withdrawal group and 7% of the nonwithdrawal group (RR 2.46; 95% CI: 0.85-7.08; p = 0.095). After withdrawal, seizure relapse rates were 27% after a median of 41 months off medication. A normal result to all 15 neuropsychological tests increased significantly from 11% to 28% postwithdrawal. We found no significant effects of withdrawal on quality of life and EEG. Predictors for remaining seizure-free after AED-withdrawal over 1 year were normal neurological examination and use of carbamazepine prior to withdrawal. Conclusion: Seizure-free epilepsy patients on AED monotherapy who taper their medication may improve neuropsychological performance with a relative risk of seizure relapse of 2.46, compared to those continuing therapy.