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Flumazenil Pretreatment in Benzodiazepine-Free Patients: A Novel Method for Managing Declining ECT Seizure Quality

Yi, James MD, PhD*; Torres, Jonathan BS*; Azner, Yuval MD*; Vaidya, Punit MD*; Schiavi, Adam MD, PhD; Reti, Irving M. MBBS*‡

doi: 10.1097/YCT.0b013e3182507752
Case Reports

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.

From the *Psychiatry and Behavioral Sciences, †Anesthesia and Critical Care Medicine, and ‡Brain Stimulation Program, Psychiatry and Neuroscience, Johns Hopkins University, Baltimore, MD.

Received for publication August 31, 2011; accepted January 30, 2012.

Reprints: Irving M. Reti, MBBS, Brain Stimulation Program, Johns Hopkins University, 600 N Wolfe St, Meyer 3-181, Baltimore, MD 21205 (e-mail:

Drs. Reti and Vaidya have received research support from NIH; HDRF; Neuronetics, Inc; and Brainsway, Inc. The other authors have no disclosures.

© 2012 by Lippincott Williams & Wilkins