Flumazenil for Benzodiazepine Reversal in Electroconvulsive Therapy

NCT07619092 | Recruiting

• 1 other identifier: 2025-522506-20-00
• Study Type: interventional
• Target: 145
• Locations: 1 country
• Sites: 1

Brief 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. 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. 2.Benzodiazepine withholding strategy (treatment as usual):

Conditions

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

Keywords

flumazenil; benzodiazepine reversal; electroconvulsive therapy; randomized controlled trial; functional magnetic resonance imaging; Autobiographical Memory Test (AMT); Inpatients; Major Depressive Disorder; Bipolar Disorder; Treatment Outcome; Cognition

Outcome Measures

Primary Outcomes (1)

• Screen for Cognitive Impairment in Psychiatry (SCIP)

  The primary outcome measure is the total score on the SCIP at follow-up (post-ECT). The SCIP is a brief neuropsychological assessment tool designed to detect cognitive deficits in individuals with psychotic and affective disorders. It comprises five subtests assessing key cognitive domains: verbal learning and memory (VLT-I and VLT-D), working memory (WMT), verbal fluency (VFT), and processing speed (PST). The total score provides a broad indicator of overall cognitive functioning. Higher scores mean a better outcome.

  Baseline (the day before the first or second session in the ECT series) and follow-up (3-7 days after completion of the ECT series)

Secondary Outcomes (19)

• Hamilton Depression Rating Scale (HDRS)

  Baseline (the day before the first or second session in the ECT series) and follow-up (3-7 days after completion of the ECT series)

• Cognitive Complaints in Bipolar Disorder Rating Scale (COBRA)

  Baseline (the day before the first or second session in the ECT series) and follow-up (3-7 days after completion of the ECT series)

• Squire Subjective Memory Questionnaire (SSMQ)

  Baseline (the day before the first or second session in the ECT series) and follow-up (3-7 days after completion of the ECT series)

• Autobiographical Memory Test (AMT)

  Baseline (the day before the first or second session in the ECT series) and follow-up (3-7 days after completion of the ECT series)

• Trail Making Test B (TMT-B)

  Baseline (the day before the first or second session in the ECT series) and follow-up (3-7 days after completion of the ECT series)

Study Arms (2)

Flumazenil for benzodiazepine reversal

EXPERIMENTAL

Participants continue benzodiazepine and/or zopiclone treatment up until the ECT session, receiving flumazenil to reverse their effects

Drug: Flumazenil

Treatment as usual (benzodiazepine hold)

ACTIVE COMPARATOR

Participants discontinue benzodiazepine and/or zopiclone treatment the day prior to the ECT session.

Procedure: Electroconvulsive therapy (ECT)

Interventions

Flumazenil DRUG

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.

Flumazenil for benzodiazepine reversal

Electroconvulsive therapy (ECT) PROCEDURE

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

Treatment as usual (benzodiazepine hold)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Current depressive episode (unipolar or bipolar), corresponding to ICD-10 codes F31.3-5, F32 or F33.
• Admitted at a study affiliated department in the Mental Health Services of the Capital Region of Denmark
• Referred to ECT by the regular psychiatrist and has given consent to ECT
• Currently receiving treatment with a benzodiazepine and/or zopiclone, at a minimum daily dose equivalent to 0.5 mg lorazepam.

You may not qualify if:

• Involuntary treatment with ECT
• Known gross abnormalities in brain structure deemed likely to influence cognitive functioning
• Pregnancy or breast-feeding
• Inability to read or understand Danish
• Acute organic brain disease (e.g., delirium) influencing the ability to give informed consent
• Any pre-existing condition associated with an increased risk of prolonged or uncontrollable seizures, including but not limited to epilepsy or alcohol- or benzodiazepine withdrawal states
• Conditions associated with reduced metabolism of flumazenil (e.g., liver failure)

Sponsors & Collaborators

• Anders Jørgensen: lead

Study Sites (1)

Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital

Frederiksberg, Capital Region, 2000, Denmark

RECRUITING

MeSH Terms

Conditions

Bipolar Disorder; Depressive Disorder, Major

Interventions

Flumazenil; Electroconvulsive Therapy

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Depressive Disorder

Intervention Hierarchy (Ancestors)

Benzodiazepinones; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Study Officials

• Anders Jørgensen, MD, Ph.D.

  Mental Health Services of the Capital Region

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stella K. S. Lystlund, MSc in Psychology

CONTACT

+ 45 21 35 40 55; stella.klara.soerensdottir.lystlund@regionh.dk

Yunus Kiros, MD

CONTACT

+ 45 81 71 95 29; yunus.kiros.02@regionh.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Consultant psychiatrist and clinical research associate professor

Study Record Dates

• First Submitted: September 24, 2025
• First Posted: June 1, 2026
• Study Start: January 15, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: June 1, 2026

Record last verified: 2026-05

Locations

DK (1)