Flumazenil for Benzodiazepine Reversal in Electroconvulsive Therapy

Summary

The goal of this study is to investigate whether administering flumazenil to reverse the effects of benzodiazepines and/or zopiclone during electroconvulsive therapy (ECT) can help reduce cognitive side effects without diminishing treatment effectiveness in hospitalized patients with depression.

The investigators hypothesize that blockade of the GABA receptor with flumazenil will reduce cognitive side effects through improved seizures and a reduced need for electrical charge escalation during the ECT series. Cognitive side effects will be measured by the total score on the Screening for Cognitive Impairment in Psychiatry (SCIP) (primary outcome) at follow-up after completion of the ECT series. Furthermore, it is expected that the flumazenil strategy will reduce pre-treatment anxiety and improve patient satisfaction (secondary outcomes). In addition, flumazenil strategy is hypothesized to have beneficial effects on subjective cognitive complaints, autobiographical memory, and executive functioning (secondary outcomes). Finally, the flumazenil strategy is expected to be associated with more favorable structural and functional changes in executive functioning and memory-related brain networks after completion of the ECT series, which may, in turn, be linked to better overall cognition and autobiographical memory (secondary outcome measures). For exploratory purposes, the study will also examine longitudinal changes in depressive symptoms and cognitive outcomes from baseline to follow-up (tertiary outcomes).

Investigators will compare two different pre-ECT benzodiazepine management strategies:

1. Flumazenil strategy (experimental): continued benzodiazepine and/or zopiclone use up until the time of the ECT session, followed by administration of flumazenil immediately prior to ECT
2. Benzodiazepine withholding strategy (treatment as usual):

discontinuation of benzodiazepines and/or zopiclone prior to the ECT in accordance with standard clinical practice

Conditions

• Depression - Major Depressive Disorder
• Bipolar Disorder (BD)
• Functional Magnetic Resonance Imaging (fMRI)
• Cognition
• Autobiographical Memory
• Electroconvulsive Therapy
• ECT
• Treatment Outcome
• Inpatients

Interventions

DRUG

Flumazenil

The intervention involves continuation of benzodiazepine and/or zopiclone treatment up to the time of ECT, followed by administration of flumazenil immediately prior to anesthesia to transiently reverse the effect of benzodiazepines and/or zopiclone. Otherwise, ECT is administered according to standard clinical procedures.

PROCEDURE

Electroconvulsive therapy (ECT)

Standard ECT treatment performed in accordance with clinical practice, with benzodiazepines and/or zopiclone withheld after 5:00 p.m. on the day before each session

Sponsors & Collaborators

• Anders Jørgensen

  lead OTHER

Principal Investigators

• Anders Jørgensen, MD, Ph.D. · Mental Health Services of the Capital Region

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-01-15

Primary Completion

2028-08-31

Completion

2028-08-31

Countries

• Denmark

Study Locations