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Sponsored by: |
National Institute of Mental Health (NIMH) |
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Information provided by: | National Institutes of Health Clinical Center (CC) |
ClinicalTrials.gov Identifier: | NCT00088699 |
This study examines whether Ketamine can cause a rapid-next day antidepressant effect in patients with Major Depression/Bipolar Disorder .
Purpose: 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.
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Condition | Intervention | Phase |
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Depression Major Depression/Bipolar Disorder |
Drug: Ketamine Drug: Riluzole Drug: FDG |
Phase II |
Study Type: | Interventional |
Study Design: | Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Efficacy Study |
Official Title: | Investigation of the Rapid (Next Day) Antidepressant Effects of an NMDA Antagonist |
Estimated Enrollment: | 144 |
Study Start Date: | July 2004 |
Bipolar affective disorder (manic-depressive illness) and unipolar depression are common, 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. In two separate trials, we tested riluzole (an inhibitor of glutamate release) and found it to have antidepressant properties in patients with unipolar and bipolar depression (Zarate et al. 2004, 2005). In another study, we found that the non-competitive NMDA antagonist (ketamine) was effective in treatment-resistant major depression. Ketamine resulted in rapid, robust and relatively sustained antidepressant effects. Response with ketamine occurred within 2 hours and last approximately 1 week (Zarate et al in press). The current protocol consists of 3 studies designed to address 3 major questions:
Study 1 (Rapid improvement research in unipolar depression):
Does the NMDA antagonist ketamine produce rapid antidepressant effects in patients with treatment-resistant major depression? 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.
Study 2 (Rapid improvement research in bipolar depression):
Does the NMDA antagonist ketamine produce rapid antidepressant effects in patients with treatment-resistant bipolar depression? Patients, ages 18 to 65 years with treatment-resistant bipolar depression will in a double-blind crossover study receive either intravenous ketamine or saline solution added to a mood stabilizer (lithium or valproate).
Study 3 (Rapid and sustained improvement research in unipolar depression):
Does riluzole (an inhibitor of glutamate release) promote and maintain response in patients with treatment-resistant major depression who have received a single intravenous dose of ketamine? Patients, ages 18 to 65 years, with treatment-resistant major (unipolar) depression who have received a single intravenous dose of ketamine will in a double-blind study receive either riluzole or placebo to determine if the rapid response obtained can be sustained.
Our primary hypotheses for these studies are: 1) rapid response (same or next day) can be achieved in patients with treatment-resistant major (unipolar) depression, 2) rapid response (same or next day) can be achieved in patients with treatment-resistant bipolar depression, and 3) rapid response (same or next day) can be sustained in patients with treatment-resistant unipolar depression.
Ages Eligible for Study: | 18 Years to 65 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
INCLUSION CRITERIA - STUDY 1:
Current major depressive episode of at least 4 weeks duration.
EXCLUSION CRITERIA - STUDY 1:
No structured psychotherapy will be permitted during the study.
INCLUSION CRITERIA - STUDY 2:
Subjects must take VPA or lithium (valproate 50-125 mg/ml or lithium 0.6-1.2 mEq/L) for at least 4 weeks prior to Visit 2. If the subject is not taking lithium or VPA, the research physician may start them on lithium or VPA at the NIH.
EXCLUSION CRITERIA - STUDY 2:
No structured psychotherapy will be permitted during the study.
INCLUSION CRITERIA - STUDY 3:
Current major depressive episode of at least 4 weeks duration.
EXCLUSION CRITERIA - STUDY 3:
Contact: Libby Jolkovsky | (877) 646-3644 | libby_jolkovsky@nih.gov |
United States, Maryland | |
National Institutes of Health Clinical Center, 9000 Rockville Pike | Recruiting |
Bethesda, Maryland, United States, 20892 |
Responsible Party: | National Institutes of Health ( Peter Herscovitch, M.D./Warren G. Magnuson Clinical Center ) |
Study ID Numbers: | 040222, 04-M-0222 |
Study First Received: | July 30, 2004 |
Last Updated: | September 15, 2008 |
ClinicalTrials.gov Identifier: | NCT00088699 |
Health Authority: | United States: Federal Government |
Depression NMDA Antagonist Treatment Resistant Glutamatergic System |
Ketamine Depression Major Depression |
Riluzole Excitatory Amino Acids Affective Disorders, Psychotic Depression Mental Disorders Bipolar Disorder |
Ketamine Mood Disorders Psychotic Disorders Depressive Disorder, Major Depressive Disorder Behavioral Symptoms |
Anesthetics, Intravenous Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Anesthetics Central Nervous System Depressants Excitatory Amino Acid Agents Anesthetics, Dissociative |
Pharmacologic Actions Sensory System Agents Anesthetics, General Therapeutic Uses Peripheral Nervous System Agents Analgesics Central Nervous System Agents Excitatory Amino Acid Antagonists |