Rapid Antidepressant Effects of Ketamine in Major Depression
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.
Major Depression/Bipolar Disorder
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
|Official Title:||Investigation of the Rapid (Next Day) Antidepressant Effects of an NMDA Antagonist|
- Evaluate the changes in neuroimaging and electrophysiological measures with ketamine treatement. [ Time Frame: 4 weeks (Study 2), 6 weeks (Study 3) ] [ Designated as safety issue: No ]
- Evaluate the effects of ketamine on depression symptoms, manic symptoms, global change in psychiatric symptoms, and suicidal ideation. [ Time Frame: 4 weeks (Study 2), 6 weeks (Study 3) ] [ Designated as safety issue: Yes ]
|Study Start Date:||July 2004|
|Estimated Study Completion Date:||April 2017|
|Estimated Primary Completion Date:||April 2017 (Final data collection date for primary outcome measure)|
Bipolar disorder and major depressive disorder (MDD) 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 MDD and bipolar depression (BD). In another study (Substudy 1), we found that the non-competitive NMDA antagonist (ketamine) was effective in treatment-resistant MDD. Ketamine resulted in rapid, robust and relatively sustained antidepressant effects. Response with ketamine occurred within 2 hours and last approximately 1 week. The current protocol consists of 4 substudies:
Substudy 1 (Rapid improvement research in MDD)
Does the NMDA antagonist ketamine produce rapid antidepressant effects in patients with treatment-resistant MDD? (Substudy 1 completed).
Substudy 2 (Rapid improvement research in bipolar depression)
Does the NMDA antagonist ketamine produce rapid antidepressant effects in patients with treatment-resistant BD? Patients, ages 18 to 65 years with treatment-resistant BD will, in a double-blind crossover study, receive either intravenous ketamine or saline solution.
Substudy 3 (Rapid and sustained improvement research in unipolar depression)
Does riluzole promote and maintain response in patients with treatment-resistant MDD who have received a single intravenous dose of ketamine? Patients, ages 18 to 65 years, with treatment-resistant MDD who have received a single intravenous dose of ketamine will, in a double-blind study, receive either riluzole or placebo.
Substudy 4 (Predictors and neural correlates of antidepressant response to ketamine)
What are the predictors and neural correlates of antidepressant response to ketamine? Patients, ages 18 to 55 years with treatment-resistant MDD and BD will, in a double-blind crossover study, receive either intravenous ketamine or saline solution and multimodal MRI, MEG and polysomnography.
Primary hypotheses are: Substudy 1) rapid response (same or next day) can be achieved in patients with treatment-resistant MDD, Substudy 2) rapid response can be achieved in patients with treatment-resistant BD, Substudy 3) rapid response can be sustained in patients with treatment-resistant unipolar depression with a glutamatergic modulator, and Substudy 4) aims are to examine the predictors and neural correlates of antidepressant response to ketamine.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00088699
|Contact: Nancy Brutsche, R.N.||(877) email@example.com|
|Contact: Carlos A Zarate, M.D.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||Carlos A Zarate, M.D.||National Institute of Mental Health (NIMH)|