Action of Ketamine in Treatment-Resistant Depression

Summary

Depression carries the largest burden of all medical disorders in middle to high income countries, as determined by the World Health Organization. Despite many antidepressant strategies, only a third of patients get well after their first treatment and a third remain ill after several treatments. Moreover, antidepressant treatments all have a delayed action ranging up to several weeks.

Ketamine (KET) has been used for decades as a sedative and anesthetic. In treatment-resistant depressed patients(TRD), an intravenous dose much lower than necessary for anesthesia may produce a robust antidepressant effect and may even abolish suicidal thoughts within hours, peaking within 24 hours. But, its antidepressant effect generally lasts only days.Previous studies examining KET in TRD have been critiqued for lack of an effective placebo measure due to brief perceptual experiences associated with KET. Thus, the current study compares KET against a short-acting sedative. The phases of this study compare response to a single KET injection to 6 injections over 2 weeks. Next, KET responders are given 1 injection a week for 3 weeks of either KET or the sedative agent to determine if beneficial effects of KET are maintained, and to assess duration of its benefits after repeated administration. The genetic profile of patients for a substance promoting contacts between cells and brain will be determined to investigate if response to KET could be predicted with that blood test. This substance, as well as several chemicals that produce inflammation, will also be measured in the blood to investigate their role in the effect of KET. Patients will receive, in total, no more than the equivalent of two to three anesthetic dose of KET. Results from this study will help establish the beneficial effects of a single KET injection as a rapid intervention for major depression, and to investigate the possibility of obtaining a prolonged antidepressant effect with repeated injections.

Conditions

• Treatment-resistant Depression

Interventions

DRUG

Ketamine

Intravenous Bolus infusion Ketamine Hydrochloride 0.50 mg/mL over 40 minutes

DRUG

Midazolam

Bolus infusion of Midazolam Hydrochloride 1 mg/mL over 40 minutes

Sponsors & Collaborators

• Canadian Institutes of Health Research (CIHR)

  collaborator OTHER_GOV

• University of Ottawa

  lead OTHER

Principal Investigators

• Pierre Blier, M.D, Ph.D · University of Ottawa

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2013-05-31

Primary Completion

2017-12-31

Completion

2017-12-31

Countries

• Canada

Study Locations