Rapid Antidepressant Effects of Ketamine in Major Depression
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|ClinicalTrials.gov Identifier: NCT00088699|
Recruitment Status : Completed
First Posted : August 2, 2004
Results First Posted : October 12, 2018
Last Update Posted : October 12, 2018
Depressive disorders may be severe, chronic and often life-threatening illnesses. Impairment in physical and social functioning resulting from depression can be just as severe as other chronic medical illnesses. Recent preclinical and clinical studies suggest that the glutamatergic system is involved in the mechanism of action of antidepressants.
This study examines whether ketamine can cause a rapid-next day antidepressant effect in patients with Major Depressive Disorder.
This study was designed to address the questions:
Does the NMDA antagonist ketamine produce rapid antidepressant effects in patients with treatment-resistant major depression? What are the neurobiological correlates of antidepressant response (examining multi-modal MRI, MEG, polysomnography and serum markers) Patients, ages 18 to 65 years with treatment-resistant major (unipolar) depression will in a double-blind crossover study receive either intravenous ketamine or saline solution.
|Condition or disease||Intervention/treatment||Phase|
|Depression Mood Disorders Major Depresssion||Drug: Ketamine Drug: Placebo||Phase 1 Phase 2|
This study will test whether a single dose of ketamine - a drug that blocks a brain receptor called NMDA - can cause a rapid (next day) antidepressant effect in patients with major depression. Several medications are effective for treating depression; however, they take weeks or months to achieve their full effects. A more rapidly acting antidepressant would have a significant impact on the treatment of depression. In a previous study, ketamine produced a rapid antidepressant effect within hours, but the effect lasted less than 1 week. Understanding how ketamine works may lead to a better understanding of the causes of depression and the design of a longer lasting rapidly acting antidepressant.
Patients between 18 and 65 years of age who are currently experiencing an episode of major depression of at least 4 weeks duration and have not responded to two treatment trials may be eligible for this study. Candidates are screened with a medical and psychiatric history, physical examination, and blood and urine tests.
Participants undergo the following tests and procedures:
Medication tapering: Patients who are taking medications for depression are tapered off the drugs over a 1- to 2-week period.
Ketamine/placebo trial: Patients are given a single dose of either ketamine or placebo (an inactive substance), administered intravenously (through a vein) over 40 minutes. After 7 days, patients are given another dose of study drug in crossover fashion; that is, those who previously took ketamine are switched to receive placebo, and those who took placebo are switched to ketamine. Oximetry (measurement of blood oxygen), pulse, and blood pressure are measured continuously for 1 hour before and 4 hours after each ketamine or placebo dose to monitor safety.
Interviews and rating scales: Patients complete a series of psychiatric rating scales to assess the effects of the study drug on mood and thinking. The rating scales are repeated up to 18 times during the study, with each time taking about 15 to 20 minutes.
Physical examination and laboratory tests: Patients have a physical examination, blood tests, weight measure, and electrocardiogram (ECG) at the beginning and end of the study. They will also have multi-modal MRI, MEG, polysomnography and serum marker studies.
The primary endpoint will be the change in clinical ratings of depression. Secondary endpoints will examine neurobiological correlates (i.e., multi-modal MRI, MEG, polysomnography and serum markers) of antidepressant response to ketamine (compared to placebo).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||67 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Investigation of the Rapid (Next Day) Antidepressant Effects of an NMDA Antagonist|
|Study Start Date :||July 26, 2004|
|Actual Primary Completion Date :||July 31, 2017|
|Actual Study Completion Date :||July 31, 2017|
Experimental: Ketamine, Then Placebo
Ketamine and placebo infusions were administered two weeks apart, with Ketamine's dose being 0.5 mg/kg.
Experimental: Placebo, Then Ketamine
Placebo and Ketamine infusions were administered two weeks apart, with Ketamine's dose being 0.5 mg/kg
- MADRS Score - Baseline [ Time Frame: Baseline ]Antidepressant effects were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). It is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60.
- MADRS Score - Day 1 Following Intervention [ Time Frame: Day 1 ]Antidepressant effects were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). It is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00088699
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Carlos A Zarate, M.D.||National Institute of Mental Health (NIMH)|