Comparison of Esketamine/Propofol and Methohexital Anesthesia for ECT

Depression Clinical Trial

— Ketofol  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05655754
• Other study ID #: BMF22114
• Status: Recruiting
• Phase: Phase 4
• Start date: November 1, 2022
• Est. completion date: October 31, 2025

Study information

• Verified date: March 2024
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: October 31, 2025
• Est. primary completion date: October 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Depression
• ECT

Intervention

Drug:
• Methohexital
anesthesia during ECT
• Ketofol
anesthesia during ECT

Locations

Country	Name	City	State
Austria	Pia Baldinger-Melich	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Vienna

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	antidepressant effect	• HAMD17 change between baseline and post-ECT in both treatment arms over a series of 8 ECT sessions	4 weeks
Primary	recovery time	Mean recovery time over 8 ECT sessions in both treatment arms	4 weeks
Secondary	adverse events	AEs during anesthesia/ECT	4 weeks
Secondary	concomitant medication	use of concom. medication during intervention to treat AEs	4 weeks
Secondary	cognition	MMSE, 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	4 weeks
Secondary	time to reorientation	compare time to reorientation in both treatment arms	4 weeks
Secondary	seizure quality	compare 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	4 weeks