Rapid Antidepressant Effects of Ketamine in Major Depression

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )
ClinicalTrials.gov Identifier:
NCT00088699
First received: July 30, 2004
Last updated: October 1, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Depression
Major Depression/Bipolar Disorder
Drug: Ketamine
Drug: Riluzole
Drug: FDG
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 324
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)
Intervention Details:
    Drug: Ketamine
    N/A
    Drug: Riluzole
    N/A
    Drug: FDG
    Radiotracer
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • STUDY POPULATION (FOR SUBSTUDY 4)

Male and female patients, ages 18 to 55 years with a diagnosis of MDD, currently depressed or in a current major depressive episode of BD without psychotic features will be recruited into this substudy. In addition, healthy volunteers will also be recruited into this substudy.

The proportion of ethnic minorities (vs. Caucasian) in the total sample will be consistent with the ethnic/racial proportions of the Washington D.C. and Montgomery county areas. We appreciate that minority groups tend to be underrepresented in research samples for mood disorders. Therefore, we make every effort to recruit minority patients, in order to ensure that the subject sample represents the community. Although it is not known whether racial differences will affect responses to pharmacotherapy, Substudy 4 will assess such effects; however, the size of the racial subsamples may be too small to identify statistically meaningful differences.

INCLUSION CRITERIA FOR PATIENTS WITH MDD OR BD:

Male or female subjects, 18 to 55 years of age.

Age of onset less than 40 years of age.

Female subjects of childbearing age must be using a medically accepted method of contraception.

Each subject must have a level of understanding sufficient to agree to all required tests and examinations and sign an informed consent document.

Subjects must fulfill DSM-IV criteria for Major Depression single episode or recurrent without psychotic features, or Bipolar Disorder (296.5 for Bipolar I Disorder or 296.89 for Bipolar II Disorder) without psychotic symptoms based on clinical assessment and confirmed by a structured diagnostic interview (SCID-P).

Subjects must have an initial score on the MADRS of at least 20 at screening, and at baseline for Phase I of Substudy 4.

Current or past history of lack of response to one adequate antidepressant trial, operationally defined using the Antidepressant Treatment History Form (ATHF); a failed adequate trial of ECT would count as an adequate antidepressant trial.

Current major depressive episode of at least 4 weeks duration.

In women of childbearing age, a negative pregnancy test within 24 hours of MRI.

EXCLUSION CRITERIA FOR PATIENTS WITH MDD OR BD:

Current psychotic features or a diagnosis of Schizophrenia or any other psychotic disorder as defined in the DSM-IV.

Subjects with a history of DSM-IV drug or alcohol dependency or abuse (except for caffeine or nicotine dependence) within the preceding 3 months. In addition, subjects who currently are using drugs (except for caffeine or nicotine) must not have used illicit substances in the 2 weeks prior to screen and must have a negative alcohol and drug urine test (except for prescribed benzodiazepines) urine test at screening.

Female subjects who are either pregnant or nursing.

Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.

Presence of any medical illness likely to alter brain morphology and/or physiology (e.g., hypertension, diabetes) even if controlled by medications.

Clinically significant abnormal laboratory tests.

Subjects with clinical hypothyroidism or hyperthyroidism.

Subjects with one or more seizures without a clear and resolved etiology.

Treatment with a reversible MAOI within two weeks prior to Phase I of Substudy 4.

Treatment with fluoxetine within five weeks or aripiprazole within three weeks before Phase I of Substudy 4.

Treatment with any other concomitant medication (Appendix 3) 14 days prior to Phase I of Substudy 4.

Presence of metallic (ferromagnetic) implants (e.g, heart pacemaker, aneurysm clip).

Subjects who, in the investigator s judgment, pose a current serious suicidal or homicidal risk, or who have a MADRS item 10 score of > 4.

No structured psychotherapy will be permitted during Substudy 4.

INCLUSION CRITERIA FOR HEALTHY CONTROL SUBJECTS:

Age 18-55 years.

Written informed consent completed.

In women of childbearing age, a negative pregnancy test within 24 hours of MRI.

EXCLUSION CRITERIA FOR HEALTHY CONTROL SUBJECTS:

Current or past Axis I diagnosis

Presence of metallic (ferromagnetic) implants (e.g., heart pacemaker, aneurysm clips).

Presence of medical illness likely to alter brain morphology and/or physiology (e.g., hypertension, diabetes) even if controlled by medications.

Treatment with any of the exclusionary medications detailed in Appendix 3 14 days prior to Phase 1 of the Substudy 4.

Current or past alcohol or substance abuse or dependence diagnosis (except for nicotine or caffeine).

Presence of psychiatric disorders in first-degree relatives.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00088699

Contacts
Contact: Nancy Brutsche, R.N. (877) 646-3644 moodresearch@mail.nih.gov
Contact: Carlos A Zarate, M.D. (301) 451-0861 zaratec@mail.nih.gov

Locations
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    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Carlos A Zarate, M.D. National Institute of Mental Health (NIMH)
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )
ClinicalTrials.gov Identifier: NCT00088699     History of Changes
Other Study ID Numbers: 040222, 04-M-0222
Study First Received: July 30, 2004
Last Updated: October 1, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Depression
NMDA Antagonist
Treatment Resistant
Glutamatergic System
Ketamine
Major Depression

Additional relevant MeSH terms:
Bipolar Disorder
Depression
Depressive Disorder
Depressive Disorder, Major
Affective Disorders, Psychotic
Behavioral Symptoms
Mental Disorders
Mood Disorders
Antidepressive Agents
Ketamine
Analgesics
Anesthetics
Anesthetics, Dissociative
Anesthetics, General
Anesthetics, Intravenous
Central Nervous System Agents
Central Nervous System Depressants
Excitatory Amino Acid Agents
Excitatory Amino Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014