N-methyl-D-aspartate Antagonist (Ketamine) Augmentation of Electroconvulsive Treatment for Severe Major Depression

NCT01260649 | Terminated Phase 4 Results

• 1 other identifier: 2010P001672
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

Electroconvulsive therapy (ECT), is considered the most effective treatment for severe treatment resistant major depressive disorder (MDD), but it requires about 3 weeks of treatments and can cause considerable acute deficits in memory. It would be a major advance in treatment if ECT could work faster with fewer treatments and result in decrease incidence of memory problems. Ketamine is an excellent candidate for augmentation of ECT because of its acute effects on depression, its short half-life, and its safety profile when given at low doses. Ketamine is given as an infusion and could easily be incorporated into the routine management of patients undergoing ECT, but has never been evaluated prospectively in this context. The investigators propose to assess the efficacy, feasibility, tolerability and safety of N-methyl-D-aspartate antagonist augmentation of ECT using ketamine.

Conditions

Major Depressive Disorder

Keywords

Electroconvulsive treatment; ketamine; Major Depression; Treatment-resistant Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• Change in Hamilton Depression Rating Scale - 28

  HAMD will be administered at every ECT treatment.The HAM D 28 is a 28 item scale with scores ranging from 0 to 83, with 0 being no depression and 83 being high levels of depression symptoms. The change in HAM S score was determined by the difference of the HAM D score at the last ECT administration and the baseline HAM D score. A negative change score reflects a decreased HAM D score between the first and last ECT administration and therefore a reduction in depressive symptoms.

  baseline, one month

Secondary Outcomes (1)

• Number of Participants With Cognitive Side Effects

  3 months

Study Arms (2)

ketamine

EXPERIMENTAL

ketamine (0.5 mg/kg) followed by anesthetic agent titrated to sedation and succinylcholine titrated to muscle relaxation Right unilateral ECT at 5-6x seizure threshold three times a week

Drug: ketamine; Procedure: ECT; Drug: Muscle Relaxant; Drug: Anesthetic Agents

placebo

PLACEBO COMPARATOR

IV saline, followed by anesthestic agent titrated to sedation and succinylcholine titrated to muscle relaxation. Right unilateral ECT at 5-6x seizure threshold three times a week

Other: IV Saline; Procedure: ECT; Drug: Muscle Relaxant; Drug: Anesthetic Agents

Interventions

ketamine DRUG

eligible patients will be randomly assigned to a double-blind administration of ketamine (0.5 mg/kg) or IV Saline, followed by the routine anesthetic agent and muscle relaxant. ECT will be administered as per standard of care

ketamine

IV Saline OTHER

eligible patients will be randomly assigned to a double-blind administration of ketamine (0.5 mg/kg) or IV Saline, followed by the routine anesthetic agent and muscle relaxant. ECT will be administered as per standard of care

placebo

ECT PROCEDURE

ECT will be administered as per standard of care

ketamine; placebo

Muscle Relaxant DRUG

All participant will receive routine course of muscle relaxant with ECT as per standard of care

ketamine; placebo

Anesthetic Agents DRUG

All participant will receive routine course of anesthetic agents with ECT as per standard of care

ketamine; placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• males and females between the ages of 18-65,
• DSM-IV diagnosis of Major Depressive Disorder (MDD), without psychotic features
• HAM-D-28 score of 20 or higher
• requiring ECT treatment as part of their psychiatric care Comorbid anxiety disorders (OCD, Generalized anxiety, panic disorder) will be allowed as long as the clinician administering the SCID believes that they are not the primary diagnosis.

You may not qualify if:

• MDD with a score of \<20 on the HAM-D 28,
• Other DSM-IV primary diagnoses including major depressive disorder with psychotic features, bipolar disorder, schizoaffective disorder, schizophrenia, dementia
• any history of psychosis
• substance use disorder (abuse or dependence with active use within the last 6 months), and any lifetime history of ketamine abuse or dependence;
• organic mental disorders;
• seizure disorder or chronic antiepileptic medications;
• severe or unstable medical illness, including history of closed head injury resulting in loss of consciousness, medical contraindication to anesthesia or to ECT (i.e. recent myocardial infarction, increased intracranial pressure)
• current treatment with memantine
• pregnancy, or females of reproductive age who are not using an accepted method of contraception (birth control pill, IUD, combination of barrier methods).
• known hypersensitivity to ketamine

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Ketamine; Sodium Chloride; Anesthetics

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Central Nervous System Depressants; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Central Nervous System Agents; Therapeutic Uses

Results Point of Contact

• Title: Dr. Cristina Cusin
• Organization: MGH

ccusin@mgh.harvard.edu

617 726 64221

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Instructor HMS

Study Record Dates

• First Submitted: December 7, 2010
• First Posted: December 15, 2010
• Study Start: November 1, 2010
• Primary Completion: October 26, 2012
• Study Completion: November 1, 2012
• Last Updated: May 22, 2017
• Results First Posted: April 14, 2017

Record last verified: 2017-04

Locations

US (1)