Major Depressive Disorder, Treatment Resistant Depression
Conditions
Keywords
ketamine, TRD, depression, electroconvulsive therapy (ECT)
Brief summary
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.
Interventions
DRUGKetamine Hydrochloride
Ketamine will be administered intravenously at a subanesthetic dose of 0.5 mg/kg after a bolus of Propofol, during ECT sessions 2, 4, and 6.
DRUGPlacebo
Placebo will be administered intravenously at a subanesthetic dose of 0.5 mg/kg after a bolus of Propofol, during ECT sessions 2, 4, and 6.
Sponsors
Università Vita-Salute San Raffaele
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean change in depressive symptoms, as measured by MADRS scale | 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 | The primary efficacy endpoint will be assessed using the MADRS score (Montgomery-Åsberg Depression Rating Scale) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Suicidal Ideation (Beck Scale for Suicide Ideation - BSSI) | 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) | To assess the effect of ketamine and ECT on suicidal ideation with Beck Scale for Suicide Ideation (BSSI) |
| Change in Anxiety Symptoms (Hamilton Anxiety Rating Scale - HAM-A) | 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) | 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) | 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) | To determine the cognitive effects of ketamine and ECT with Brief Assessment of Cognition in Affective Disorders (BAC-A) |
| Change in Dissociative and Psychotic Symptoms (Clinician-Administered Dissociative States Scale - CADSS; Brief Psychiatric Rating Scale - BPRS) | 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 | 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) |
| Change in Neurochemical Markers (Plasma Levels of Trp, 5-HT, 5-HIAA, Glutamate, Aspartate) | Assessment will be performed at: Baseline (Day 0, before first ECT session); Weekly during ECT treatment period (Weeks 1, 2, 3) | 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. |
Countries
Italy
Contacts
CONTACTAlberto AZ Zangrillo, MD
CONTACTCristina CC Colombo, MD
PRINCIPAL_INVESTIGATORAlberto AZ Zangrillo, MD
Università Vita-Salute San Raffaele
PRINCIPAL_INVESTIGATORCristina CC Colombo, MD
IRCCS Ospedale San Raffaele Turro
Outcome results
None listed