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Flumazenil for Benzodiazepine Reversal in Electroconvulsive Therapy (FLEET)

27 de maio de 2026 atualizado por: Anders Jørgensen

Flumazenil for Benzodiazepine Reversal in Electroconvulsive Therapy (FLEET): A Randomized Controlled Trial

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

Visão geral do estudo

Status

Recrutamento

Condições

Intervenção / Tratamento

Descrição detalhada

The study will include adult inpatients (≥18 years of age) diagnosed with a mood disorder (major depressive disorder or bipolar disorder), currently experiencing a depressive episode (ICD-10: F31.3-5, F32 or F33), who are deemed eligible for ECT by a treating psychiatrist who is not affiliated with the study. Based on a power analysis, 132 participants (66 per group) are required to achieve adequate statistical power. To account for an anticipated 10% dropout rate from baseline to follow-up, the investigators will recruit 145 participants. Recruitment will be carried out through psychiatric hospital wards within the Mental Health Services of the Capital Region of Denmark.

Participants will be randomized following an initial screening to confirm eligibility. Randomization will be conducted using the automated randomization module in the Research Electronic Data Capture (REDCap) system, based on a pre-generated randomization list with variable block sizes of two and four. Allocation will be stratified by age (< 60 or ≥ 60 years) and electrode placement (unilateral vs. bilateral). Randomization will occur no later than the day prior to the second ECT session of the treatment series. Primary outcome assessors are blinded to the group allocation.

Baseline assessments will be conducted the day before the first ECT session or, if not otherwise possible, the day before the second ECT session. Participants will complete a brief neuropsychological assessment comprising the Screen for Cognitive Impairment in Psychiatry (SCIP) and additional measures of executive functioning and autobiographical memory. Participants will also complete self-report questionnaires assessing subjective cognitive complaints. Depressive symptom severity will be rated using the Hamilton Depression Rating Scale (HDRS).

During the ECT treatment series, repeated assessments will be conducted for each session. Participants will provide self-reported ratings of pre-treatment anxiety shortly before the session, while clinicians will record measures of seizure architecture, and time to reorientation following the session.

Follow-up assessments will be conducted 3-7 days after completion of the ECT-series, which serves as the primary end point. At follow-up, the brief neuropsychological assessment, self-report questionnaires, and HDRS ratings will be repeated. Participants will also complete a short self-report questionnaire of their treatment satisfaction. Structural and functional magnetic resonance imaging (MRI) is conducted within the 3-7 days after completion of the ECT series, coinciding with the follow-up assessment.

Tipo de estudo

Intervencional

Inscrição (Estimado)

145

Estágio

  • Não aplicável

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Contato de estudo

Estude backup de contato

Locais de estudo

  • Dinamarca
    • Capital Region
      • Frederiksberg, Capital Region, Dinamarca, 2000
        • Recrutamento
        • Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

  • Adulto
  • Adulto mais velho

Aceita Voluntários Saudáveis

Não

Descrição

Inclusion criteria:

  • 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.

Exclusion criteria:

  • 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)

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: Randomizado
  • Modelo Intervencional: Atribuição Paralela
  • Mascaramento: Solteiro

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: Flumazenil for benzodiazepine reversal
Participants continue benzodiazepine and/or zopiclone treatment up until the ECT session, receiving flumazenil to reverse their effects
Medicamento: 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.
Comparador Ativo: Treatment as usual (benzodiazepine hold)
Participants discontinue benzodiazepine and/or zopiclone treatment the day prior to the ECT session.
Procedimento: 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

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Screen for Cognitive Impairment in Psychiatry (SCIP)
Prazo: 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)
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)

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Hamilton Depression Rating Scale (HDRS)
Prazo: 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)
Clinician-administered depression assessment scale of 17 items. Score range: 0-52. Clinical response at follow-up (primary endpoint) is assessed using the HAM-D6 subscale, collectively comprising the core symptoms of depression with score range: 0-22. Higher scores mean a worse 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)
Cognitive Complaints in Bipolar Disorder Rating Scale (COBRA)
Prazo: 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)
Self-report questionnaire assessing subjective cognitive complaints. Score range: 0-48. Higher scores mean a worse 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)
Squire Subjective Memory Questionnaire (SSMQ)
Prazo: 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)
Self-report questionnaire assessing subjective memory complaints. Score range: -72 - +72. Higher (more positive) 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)
Autobiographical Memory Test (AMT)
Prazo: 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)
Neuropsychological instrument used to assess the ability to retrieve autobiographical memories and their specificity. 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)
Trail Making Test B (TMT-B)
Prazo: 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)
Neuropsychological test assessing executive function. Scored by time to completion. Higher scores mean a worse 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)
Verbal learning and memory (VLT-I)
Prazo: 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)
SCIP subtest assessing verbal learning and immediate recall. Score range: 0-30. 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)
Delayed verbal recall (VLT-D)
Prazo: 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)
SCIP subtest assessing delayed verbal recall. Score range: 0-10. 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)
Working memory test (WMT)
Prazo: 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)
SCIP subtest assessing working memory capacity. Score: 0-24. 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)
Verbal fluency test (VFT)
Prazo: 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)
SCIP subtest assessing verbal fluency. No score range. 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)
Processing speed test (PST)
Prazo: 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)
SCIP subtest assessing processing speed. Score range: 0-30. 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)
Patient Satisfaction Survey (PSS)
Prazo: Follow-up (3-7 days after completion of the ECT series)
Self-report questionnaire assessing patient satisfaction following ECT treament. A subset of items are used. Higher scores mean a better outcome.
Follow-up (3-7 days after completion of the ECT series)
Visual Analogue Scale for Anxiety (VAS-A)
Prazo: Per ECT session
Visual analogue self-report scale assessing anxiety severity within the last 24 hours. Score range: 0-100. Higher scores mean a worse outcome.
Per ECT session
Time to reorientation
Prazo: Per ECT session
Clinician-administered structured interview measuring time to reorientation (in minutes) according to Sobin et al. (1995) and Stuiver et al. (2024). Patients are screened every 5 minutes after EEG-offset for orientation in five domains: name, location, age, date of birth, and day of the week. Reorientation is defined as the time in minutes from EEG-offset until the patient provides at least 4 out of 5 correct answers. If the patient fails to reach reorientation within 60 minutes, a score of 70 minutes is registered. Higher scores indicate a longer recovery period and a worse outcome.
Per ECT session
Seizure quality
Prazo: Per ECT session
Clinician-rated categorical EEG classification of seizure quality (A, A-T, T, O, S). A-seizures represent the optimal therapeutic pattern.
Per ECT session
Seizure length (EEG)
Prazo: Per ECT session
EEG seizure duration (seconds) from the end of stimulation to the last unequivocal ictal discharge. Continuous physiological measure.
Per ECT session
Stimulus dose
Prazo: Per ECT session
Stimulus dose recorded as the percentage of the device's maximum output (%) delivered during each treatment, as displayed on the ECT device readout. Range: 0-200%.
Per ECT session
Prefrontal and medial temporal activation during autobiographical memory retrieval
Prazo: Follow-up (3-7 days after completion of the ECT series)
Functional magnetic resonance imaging (fMRI) measure of brain activity during an autobiographical memory test
Follow-up (3-7 days after completion of the ECT series)
Prefrontal, parietal and medial temporal activation during memory encoding
Prazo: Follow-up (3-7 days after completion of the ECT series)
Functional magnetic resonance imaging (fMRI) measure of brain activity during a memory encoding task
Follow-up (3-7 days after completion of the ECT series)
Prefrontal and parietal activation during spatial N-back
Prazo: Follow-up (3-7 days after completion of the ECT series)
Functional magnetic resonance imaging (fMRI) measure of brain activity during a working memory task
Follow-up (3-7 days after completion of the ECT series)

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Anders Jørgensen

Investigadores

  • Investigador principal: Anders Jørgensen, MD, Ph.D., Mental Health Services of the Capital Region

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

15 de janeiro de 2026

Conclusão Primária (Estimado)

1 de agosto de 2028

Conclusão do estudo (Estimado)

1 de agosto de 2028

Datas de inscrição no estudo

Enviado pela primeira vez

24 de setembro de 2025

Enviado pela primeira vez que atendeu aos critérios de CQ

27 de maio de 2026

Primeira postagem (Real)

1 de junho de 2026

Atualizações de registro de estudo

Última Atualização Postada (Real)

1 de junho de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

27 de maio de 2026

Última verificação

1 de maio de 2026

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • 2025-522506-20-00

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Não

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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