ECT vs. Esketamine (ETES)

Electroconvulsive Therapy vs. Esketamine Nasal Spray in Treatment-resistant Depression: a Longitudinal, Randomized Efficacy Comparison Pilot Study

Treatment-resistant depression (TRD) is a common cause of disability and one of the most common psychiatric disorders worldwide.

Electroconvulsive therapy (ECT) is currently the most effective treatment for TRD. Recent developments showed esketamine to be a rapid-acting and effective antidepressant drug and it has been hailed as a breakthrough in treating TRD. Common treatment algorithms for TRD list ECT as a treatment option, but esketamine has not yet found its exact position in those algorithms.

To the investigators' knowledge, a longitudinal, randomized controlled trial comparing the efficacy of ECT and intranasal esketamine in TRD patients has not been conducted. Furthermore, the investigators intend to measure effects of ECT and intranasal esketamine on brain connectivity and structure, using functional magnetic resonance imaging (fMRI).

In this study, inpatients with TRD at the University Hospital for Psychiatry I, Medical University Innsbruck, will be randomized to ECT or intranasal esketamine. Short- and medium-term treatment effects on functional and structural connectivity in the brain will be determined using fMRI.

Study Overview

• Status: Withdrawn
• Conditions: Major Depressive Disorder; Treatment Resistant Depression
• Intervention / Treatment: Drug: Esketamine nasal spray; Procedure: Electroconvulsive therapy

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Tyrol
    • Innsbruck, Tyrol, Austria, 6020
      • Medical University Innsbruck

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. DSM-5 diagnosis of Major Depressive Disorder (MDD) without psychotic features (296.22, 296.23, 296.32, 296.33) made through the Structured Clinical Interview for the DSM-V (SCID-V).
2. MADRS score ≥ 25
3. Pharmacologically treatment-resistant depressive episode [Stage ≥ II, defined by Thase & Rush (1997): failure of at least 2 adequate trials of at least 2 distinctly different classes of antidepressants (≥ 4 weeks each)] (88).
4. Age: 18 - 50 years
5. Written informed consent

Exclusion Criteria:

1. Participation in another interventional clinical trial
2. Relative contraindications to ECT treatment in accordance with the consensus paper of the Austrian Society of Psychiatry and Psychotherapy:
3. Patients who meet any exclusion criteria for nasal esketamine treatment as described in the clinical guidelines
4. Contraindications to the conduction of MRI

5. History of one or more of the following diagnoses (DSM-5):

   • MDD, single or recurrent episode with psychotic features (296.24; 296.34)
   • past or current substance dependence (except caffeine, nicotine) (303.x, 304.x, 305.x)
   • neurodevelopmental disorders (299.x, 307.x, 314.x, 315.x, 319.x)
   • schizophrenia spectrum and other psychotic disorders (293.x, 295.x, 297.x, 298.x)
   • neurocognitive disorders (290.x, 292.x, 294.x, 331.x).
6. history of ECT (unsuccessful or successful)
7. suicidal tendency requiring admission in a locked ward
8. pregnancy or lactation period
9. lack of anesthetic clearance for any other reason
10. insufficient command of German language.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Intranasal Esketamine	Drug: Esketamine nasal spray; Patients will receive two treatments per week for four weeks (maximum of eight treatment sessions) or until clinical remission (MADRS <10).
ACTIVE_COMPARATOR: ECT	Procedure: Electroconvulsive therapy; Patients will receive three treatments per week for four weeks (maximum of 12 ECT treatments) or until clinical remission (MADRS <10).; Other Names: ECT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MADRS score	Reduction of Montgomery-Asberg Depression Rating Scale (MADRS, 0-60 pts.); higher score indicates more depressive symptoms; response to treatment is defined as >50% reduction in score	4 weeks

Collaborators and Investigators

• Sponsor: Medical University Innsbruck

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 28, 2021
• Primary Completion (ANTICIPATED): August 1, 2023
• Study Completion (ANTICIPATED): April 1, 2024

Study Registration Dates

• First Submitted: June 7, 2021
• First Submitted That Met QC Criteria: June 7, 2021
• First Posted (ACTUAL): June 11, 2021

Study Record Updates

• Last Update Posted (ACTUAL): August 5, 2022
• Last Update Submitted That Met QC Criteria: August 2, 2022
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Psychotropic Drugs; Antidepressive Agents; Esketamine
• Other Study ID Numbers: 1417/2020

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No