Flumazenil pretreatment in benzodiazepine-free patients: A novel method for managing declining ECT seizure quality

Objective: Seizure threshold increases with successive electroconvulsive therapy (ECT) treatments, which can be especially problematic when treating older patients who have higher seizure thresholds at baseline because ECT devices are limited by the amount of charge that can be delivered. Case Reports: We present a case series of 3 older patients who had long ECT courses that were complicated by inability to generate seizures, poor quality seizures, and inadequate clinical response despite established measures to lower seizure threshold including prehydration, hyperventilation, and minimizing methohexital dose using remifentanil. As preclinical studies show electroconvulsive seizure increases diazepam binding, we hypothesized that a contributor to declining seizure quality and inadequate ECT responsiveness in these individuals was enhanced benzodiazepine receptor function, although none of the 3 patients were taking benzodiazepines or any other anticonvulsant medication. Accordingly, we pretreated patients with flumazenil, a competitive inhibitor at the benzodiazepine-binding site, and observed improvement in seizure quality and clinical response. Conclusion: Flumazenil pretreatment of elderly ECT patients with declining seizure quality and inadequate clinical response in the setting of repeated treatments may represent a novel strategy for managing such patients. A clinical trial would be required to test this hypothesis.