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
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.
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
Parallel
Flumazenil
DrugThe 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.
Electroconvulsive therapy (ECT)
Procedure/SurgeryStandard 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
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.
Hamilton Depression Rating Scale (HDRS)
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.
Cognitive Complaints in Bipolar Disorder Rating Scale (COBRA)
Self-report questionnaire assessing subjective cognitive complaints. Score range: 0-48. Higher scores mean a worse outcome.
Squire Subjective Memory Questionnaire (SSMQ)
Self-report questionnaire assessing subjective memory complaints. Score range: -72 - +72. Higher (more positive) scores mean a better outcome.
Autobiographical Memory Test (AMT)
Neuropsychological instrument used to assess the ability to retrieve autobiographical memories and their specificity. Higher scores mean a better outcome.
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Anders Jørgensen
Lead sponsor
Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital
Sponsor institution
