title: Flumazenil pretreatment in benzodiazepine-free patients: a novel method for managing declining ECT seizure quality.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Psychiatry and Behavioral Sciences, Psychiatry and Neuroscience, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: James
authors.initials: J
authors.lastname: Yi
authors.forename: Jonathan
authors.initials: J
authors.lastname: Torres
authors.forename: Yuval
authors.initials: Y
authors.lastname: Azner
authors.forename: Punit
authors.initials: P
authors.lastname: Vaidya
authors.forename: Adam
authors.initials: A
authors.lastname: Schiavi
authors.forename: Irving M
authors.initials: IM
authors.lastname: Reti
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001569:Benzodiazepines; D003131:Combined Modality Therapy; D003865:Major Depressive Disorder / Q000523:psychology / Q000628:therapy; D004305:Dose-Response Relationship, Drug; D004565:Electroconvulsive Therapy / Q000379:methods*; D004569:Electroencephalography; D005260:Female; D005442:Flumazenil / Q000627:therapeutic use*; D018757:GABA Modulators / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D011618:Psychotic Disorders / Q000150:complications / Q000523:psychology; D011963:Receptors, GABA-A / Q000187:drug effects; D012008:Recurrence; D012640:Seizures / Q000503:physiopathology / Q000523:psychology; D017211:Treatment Failure
chemical_list: D018757:GABA Modulators; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D005442:Flumazenil