A Study of Ketamine as an Antidepressant

Study Overview
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Brief Summary
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Recently, interest has emerged in the use of ketamine as an antidepressant. Recent placebo-controlled clinical trials administering a single dose and an open label trial giving repeated doses shown that ketamine is markedly superior to placebo at reducing depression, including in treatment-resistant patients, and that its antidepressant effects have a very rapid onset. This clinical study consists of two phases. In Phase I, participants who satisfy inclusion criteria will receive ketamine at variable doses (0.1mg/kg-0.5mg/kg) or a placebo (saline, or 0.01mg/kg midazolam) once a week over up to 6 weeks. If participants qualify for Phase II, they will receive repeated sessions of ketamine at variable doses over three weeks. During both phases, mood, psychiatric, and neuropsychological outcomes will be measured.

Detailed Description
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This clinical study consists of two phases. In Phase I, participants will receive variable doses of intravenous, intramuscular, or subcutaneous ketamine (0.1-0.5mg/kg) or placebo (saline, or 0.01mg/kg midazolam) weekly for up to 6 consecutive weeks. Prior to receiving ketamine/placebo, participants' mood and psychiatric symptoms will be assessed. Once they have received their treatment, mood, psychiatric side effects, ketamine blood levels, heart rate, blood pressure and biomarkers will be assessed. Mood and cognitive performance be assessed again after 4 hours. Finally, mood will also be assessed the next day. Some participants may be eligible to continue to Phase II. In this phase, participants will receive doses of ketamine approximately weekly for up to 6 months. During this phase, participants' mood, psychiatric, biomarkers and cognitive outcomes will be assessed. The purpose of the trial is to investigate the antidepressant and safety effects of using ketamine as a treatment in depression.

Official Title
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A Study of Ketamine as an Antidepressant

Conditions
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Major Depressive Episode

Intervention / Treatment
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* Drug: Ketamine
* Drug: Saline or Midazolam (active placebo)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Satisfy DSM-IV-TR criteria for Major Depressive Episode 18 years or over Able to give informed consent Exclusion Criteria: Diagnosis of schizophrenia, schizoaffective disorder, rapid cycling bipolar disorder, or current psychotic symptoms Known sensitivity or contraindication to ketamine Recent drug abuse Pregnant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Ketamine|Ketamine IV, IM, or SC will be administered in Phase I and II|
|Drug: Saline or Midazolam (active placebo)|Saline, or midazolam 0.01mg/kg will be administered in Phase I|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline on depression rating scales |  | Before, 4 hours after, and 24 hours after ketamine session | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Psychiatric side effects (BPRS, CADSS) and memory tests |  | Cognitive battery done before and after 3 weeks; side effects measured immediately before and 4 hours after each ketamine session in both phases. |