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Comparison of Esketamine/Propofol and Methohexital Anesthesia for ECT

A Prospective Randomized, Double Blind, Controlled, Safety and Non-inferiority Study of Esketamine Plus Propofol Compared to Methohexital Anesthesia for Electroconvulsive Therapy

Status
Recruiting
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT05655754
Acronym
Ketofol
Enrollment
100
Registered
2022-12-19
Start date
2022-11-01
Completion date
2025-10-31
Last updated
2025-05-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

ECT, Depression

Keywords

electroconvulsive therapy, depression, esketamine, anesthesia

Brief summary

The current anesthetic drug used as standard for ECT procedure at the Department of Psychiatry and Psychotherapy, Medical University of Vienna, is the barbiturate methohexital (Brevital®). As far as we know, methohexital is the most common anesthetic in the procedure of ECT. Only few heterogeneous randomized controlled trials to directly compare the use of (sole) ketamine and methohexital in ECT with relatively small sample sizes have been conducted so far, showing inconclusive findings: a retrospective comparison of methohexital and switch to ketamine anesthesia in 36 patients showed that ketamine prolonged seizure duration and accelerated posttreatment orientation. Others compared both drugs in terms of recovery and reorientation time showing that reorientation time was faster in the methohexital group (total N=9). Another study showed no difference in any outcome measure (depressive symptom improvement, cognition, adverse events) between both groups (total N=16, N=9 per group). Finally, a comparative investigation (total N=37, N=20 vs. N=17) detected no differences between both anesthetics but a higher systolic blood pressure posttreatment and longer motor seizure duration in the ketamine group. A favorable profile of ketamine in regards to seizure quality has been reported, however in terms of outcome measures methohexital and ketamine were similar (total N=50, N=23 vs. N=27). The present study is designed as a prospective randomized non-inferiority trial comparing esketamine plus propofol (ratio 1:1, for better readability from now on referred to as ketofol) to methohexital, the latter being the current standard anesthetic applied for ECT procedure at our department. Patients eligible for ECT will be randomly assigned to receive anesthesia with either ketofol or methohexital for the whole course of the individual ECT series. Group differences will be investigated both in regards to outcomes related to anesthesia, treatment-outcome and seizure quality. Further, changes in cardiac enzyme levels before and after ECT-treatment and during the entire ECT series will be evaluated and possible group differences will be explored. As stated above the sole/adjunct administration of ketamine as anesthetic agent for ECT has been associated with better seizure quality, similar antidepressant outcomes and anesthesia-associated events, while there is some evidence suggesting that the use of ketamine might present some advantages to other anesthetics in terms of cognitive side-effects accompanying ECT. Therefore, the aim of the present study will be to establish ketofol as a new standard for anesthesia at our Department.

Interventions

anesthesia during ECT

anesthesia during ECT

Sponsors

Medical University of Vienna
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)

Masking description

Randomization of the study drug will be done using the software www.meduniwien.ac.at/randomizer according to consecutive CRF numbers. Stratification according to baseline HAMD17 scores (3 groups: HAMD 23-30, HAMD 30-40, HAMD\>40), age and previous ECT (yes/no) will be performed Participants and treating psychiatrists will be unaware or the anesthetic used; anesthetists will know the substance that it aministered during ECT

Intervention model description

Depressive patients, that are eligible for ECT, will be randomized to receiving either ECT with esketamine plus propofol or methohexital anesthesia for the whole series (min. 8 treatments). Participants and treating psychiatrists will be unaware or the anesthetic used; anesthetists will know the substance that it aministered during ECT. Both drugs will be compared in terms of safety, recovery time and clinical outcome.

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

* male or female inpatients * age ≥ 18 years * ICD-11 diagnosis of severe uni- or bipolar depression (F32.2, F32.2, F33.2, F33.3, F31.4, F31.5) * Hamilton Depression Rating Scale HAMD17 ≥ 24 * ability to understand and willingness to sign written informed consent document * negative urine pregnancy test in women * anesthesiological approval for ECT (Classification of the American Society of Anesthesiologists ASA ≤ 3) * antidepressant and antipsychotic medication in steady state for at least 7 days prior to first ECT treatment

Exclusion criteria

* severe somatic or neurological disease (esp. current or previous history of intracranial hypertension, uncontrolled severe hypertension, bleeds or aneurysm, recent myocardial infarction) * current or past history of schizophrenia or schizoaffective disorder * clinical relevant abnormalities on a general physical examination and routine laboratory screening * pregnancy, breast feeding * known allergy to the study drugs or compounds of the latter

Design outcomes

Primary

MeasureTime frameDescription
antidepressant effect4 weeks• HAMD17 change between baseline and post-ECT in both treatment arms over a series of 8 ECT sessions
recovery time4 weeksMean recovery time over 8 ECT sessions in both treatment arms

Secondary

MeasureTime frameDescription
cognition4 weeksMMSE, Beck's Depression Inventory (BDI), multiple-choice word test (MWT-B), trail making test (TMT), reaction test (RT), cognitrone (COG), non-verbal learning test (NVLT), verbal learning test (VLT) (Vienna testing system, https://vts.schuhfried.com), compare cognitive outcomes before and after ECT in both treatment arms
adverse events4 weeksAEs during anesthesia/ECT
seizure quality4 weekscompare a function of seizure duration, concordance (seizure duration in the electromyogram/seizure duration in the electroencephalogram), midictal amplitude, peak heart rates and interhemispheric coherence in both treatment arms
time to reorientation4 weekscompare time to reorientation in both treatment arms
concomitant medication4 weeksuse of concom. medication during intervention to treat AEs

Countries

Austria

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026