Ketamine Augmentation of ECT in Treatment-Resistant Depression

Phase 3RecruitingNCT07088380

Università Vita-Salute San Raffaele30 enrolled

Overview

This is a randomized, double-blind, placebo-controlled phase 3 clinical trial evaluating the additive effect of intravenous ketamine in combination with electroconvulsive therapy (ECT) in patients with treatment-resistant major depressive disorder (MDD). The study aims to determine whether ketamine enhances the antidepressant efficacy of ECT and reduces associated cognitive side effects. Thirty hospitalized patients diagnosed with treatment-resistant MDD will be randomized to receive either ketamine or placebo (saline) during ECT sessions 2, 4, and 6. Primary outcome is the change in depressive symptoms, measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) at 4 weeks.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Major Depressive Disorder Treatment Resistant Depression

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Male and female subjects ages 18-70, * diagnosed with MDD (according to SCID5-CV interview) * treatment resistant (defined as at least 2 different antidepressant agents used without success), * ability to give informed consent, * adequacy of the score for anesthesia. Exclusion Criteria: * Chronic neurological diseases, * Intellectual disability * Contraindications to the electroconvulsive therapy (severe aortic valve stenosis, implantable cardiac defibrillators, uncontrolled hypertension, clinically significant respiratory, renal or hepatic disease, abdominal aortic aneurysm, endocrine disorders, neuromuscular diseases, space occupying brain lesions, stroke in the last 6 months), * Patients with Alcohol Use Disorder or Substance Use Disorder or Substance Abuse history in the past year, * Pregnancy and lactation * Cardiovascular conditions, * Psychiatric Disorders, * Hepatic impairment, * Participants with a known hypersensitivity to ketamine or any of its excipients will be excluded from the study, * Participants with any contraindications to the use of ketamine, such as a history of severe cardiovascular conditions (e.g., uncontrolled hypertension, significant arrhythmias), intracranial hypertension, or severe liver impairment, will also be excluded to prevent potential adverse events.

Outcomes

Primary Outcomes

Mean change in depressive symptoms, as measured by MADRS scale

The primary efficacy endpoint will be assessed using the MADRS score (Montgomery-Åsberg Depression Rating Scale)

Time frame: From baseline (day 0) to day 28 (7 days after the last ECT session). A follow-up assessment at Week 12 (90 days) will be included

Secondary Outcomes

Change in Suicidal Ideation (Beck Scale for Suicide Ideation - BSSI)

To assess the effect of ketamine and ECT on suicidal ideation with Beck Scale for Suicide Ideation (BSSI)

Time frame: Assessment will be performed at: baseline (day 0); Weekly during ECT treatment period (Weeks 1, 2, 3); Week 4 (1 week after last ECT session); Follow-up: Week 12 (3 months after last ECT session)

Change in Anxiety Symptoms (Hamilton Anxiety Rating Scale - HAM-A)

To evaluate the impact of ketamine and ECT on anxiety symptoms with Hamilton Anxiety Rating Scale (HAM-A)

Change in Cognitive Function (Brief Assessment of Cognition in Affective Disorders - BAC-A)

To determine the cognitive effects of ketamine and ECT with Brief Assessment of Cognition in Affective Disorders (BAC-A)

Time frame: Assessment will be performed at: baseline (day 0); Week 4 (1 week after last ECT session); Follow-up: Week 12 (3 months after last ECT session)

Change in Dissociative and Psychotic Symptoms (Clinician-Administered Dissociative States Scale - CADSS; Brief Psychiatric Rating Scale - BPRS)

To assess the effects of ketamine and ECT on dissociative and psychotic symptoms with Clinician-Administered Dissociative States Scale (CADSS) and Brief Psychiatric Rating Scale (BPRS)

Time frame: Assessment will be performed at: Baseline (Day 0, before first ECT session); Week 1 (After ECT session 2); Week 2 (After ECT session 4); Week 3 (After ECT session 6); Week 4 (1 week after last ECT session); Follow-up: Week 12 (3 months after last ECT

Change in Neurochemical Markers (Plasma Levels of Trp, 5-HT, 5-HIAA, Glutamate, Aspartate)

To evaluate the neurochemical effects of ketamine and ECT with High-Performance Liquid Chromatography (HPLC) analysis of plasma samples. Change in plasma levels of Trp, 5-HT, 5-HIAA, glutamate, and aspartate from baseline to Week 3 will be assessed.

Time frame: Assessment will be performed at: Baseline (Day 0, before first ECT session); Weekly during ECT treatment period (Weeks 1, 2, 3)

Central Contacts

Alberto AZ Zangrillo, MD

CONTACT

0226436154 zangrillo.alberto@hsr.it

Cristina CC Colombo, MD