Exploring postictal recovery with acetaminophen or nimodipine: A randomized-controlled crossover trial

Objective: The postictal state is underrecognized in epilepsy. Animal models show improvement of postictal symptoms and cerebral perfusion with acetaminophen or nimodipine. We studied the effects of acetaminophen or nimodipine on postictal electroencephalographic (EEG) recovery, clinical reorientation, and hypoperfusion in patients with ECT-induced seizures. Methods: In this prospective clinical trial with three-condition randomized crossover design, study interventions were administered orally 2 h before ECT sessions (1000 mg acetaminophen, 60 mg nimodipine, or a placebo condition). Primary outcome measure was the speed of postictal EEG recovery. Secondary outcomes were the extent of postictal EEG recovery, clinical reorientation time, and postictal cerebral blood flow as assessed by perfusion-weighted MRI. Bayesian generalized mixed-effects models were applied for analyses. Results: We included 300 seizures, postictal EEGs, and reorientation time values, and 76 MRI perfusion measures from 33 patients (median age 53 years, 19 female). Pretreatment with acetaminophen or nimodipine was not associated with change in speed of EEG recovery compared to placebo (1.13 [95%CI 0.92, 1.40] and 1.07 [95%CI 0.87, 1.31], respectively), nor with the secondary outcomes. No patient reached full EEG recovery at 1 h post-seizure, despite clinical recovery in 89%. Longer seizures were associated with slower EEG recovery and lower postictal perfusion. Nimodipine altered regional perfusion in the posterior cortex. Interpretation: Pretreatment with acetaminophen or nimodipine did not alleviate symptoms and signs of the postictal state. Systematic study of the postictal state after ECT-induced seizures is feasible.