Depression Clinical Trial
Official title:
Investigation of the Rapid (Next Day) Antidepressant Effects of an NMDA Antagonist
Verified date | July 31, 2017 |
Source | National Institutes of Health Clinical Center (CC) |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 67 |
Est. completion date | July 31, 2017 |
Est. primary completion date | July 31, 2017 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 65 Years |
Eligibility |
- INCLUSION CRITERIA: General patient inclusion criteria 1. Male or female subjects, 18 to 65 years of age. 2. Each subject must have a level of understanding sufficient to agree to all required tests and examinations and sign an informed consent document. 3. Subjects must fulfill DSM-IV criteria for Major Depressive Disorder (MDD) without psychotic features, based on clinical assessment and confirmed by a structured diagnostic interview, SCID-P. 4. Subjects must have an initial score of at least 20 on the MADRS at screen and at baseline of study phase I. 5. Subjects must have failed to respond in the past to an adequate dose and duration of at least one antidepressant (SSRI, bupropion, or venlafaxine) during a depressive episode 6. Current depressive episode of at least 4 weeks duration. Additional inclusion criteria for substudy 4 (patients with MDD) 1. Age of onset less than 40 years of age. 2. Subjects with MDD must fulfill DSM-IV criteria for Major Depression single episode or recurrent without psychotic features based on clinical assessment and confirmed by a structured diagnostic interview (SCID-P). 3. A failed adequate trial of ECT would count as an adequate antidepressant trial. 4. In women of childbearing age, a negative pregnancy test within 24 hours of MRI. Inclusion criteria for healthy control subjects (Substudy 4 only) 1. Age 18-65 years. 2. Written informed consent completed. EXCLUSION CRITERIA: General patient exclusion criteria 1. Current or past diagnosis of Schizophrenia or any other psychotic disorder as defined in the DSM-IV. 2. Subjects with a history of DSM-IV drug or alcohol dependency or abuse (except for nicotine or caffeine) within the preceding 3 months. 3. Female subjects who are either pregnant or nursing. 4. Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease. 5. Subjects with uncorrected hypothyroidism or hyperthyroidism. 6. Subjects with one or more seizures without a clear and resolved etiology. 7. Treatment with a reversible MAOI within 4 weeks prior to study phase I. 8. Treatment with fluoxetine within 5 weeks prior to study phase I. 9. Treatment with any other concomitant medication not allowed (Appendix A for Substudy 2; Appendix G for Substudy 4) 14 days prior to study phase I. 10. No structured psychotherapy will be permitted during the study. 11. Current NIMH employee/staff or their immediate family member. Additional Exclusion Criteria for substudy 2 (patients with MDD) 1. Previous treatment with ketamine or hypersensitivity to amantadine. Additional Exclusion Criteria for Substudy 4 (patients with MDD) 1. 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. 2. Presence of any medical illness likely to alter brain morphology and/or physiology (e.g., hypertension, diabetes) even if controlled by medications. 3. Clinically significant abnormal laboratory tests. 4. For imaging procedures, Presence of metallic (ferromagnetic) implants (e.g, heart pacemaker, aneurysm clip). 5. 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. Exclusion Criteria for healthy control subjects (Substudy 4 only) 1. Current or past Axis I diagnosis 2. Presence of metallic (ferromagnetic) implants (e.g., heart pacemaker, aneurysm clips). 3. Presence of medical illness likely to alter brain morphology and/or physiology (e.g., hypertension, diabetes) even if controlled by medications. 4. Treatment with any of the exclusionary medications detailed in Appendix G 14 days prior to Phase 1 of the Substudy 4. 5. Current or past alcohol or substance abuse or dependence diagnosis (except for nicotine or caffeine). 6. Presence of psychiatric disorders in first-degree relatives. 7. Female subjects who are either pregnant or nursing. 7.8.Current NIMH employee/staff or their immediate family member. |
Country | Name | City | State |
---|---|---|---|
United States | National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland |
Lead Sponsor | Collaborator |
---|---|
National Institute of Mental Health (NIMH) |
United States,
Evans JW, Lally N, An L, Li N, Nugent AC, Banerjee D, Snider SL, Shen J, Roiser JP, Zarate CA Jr. 7T (1)H-MRS in major depressive disorder: a Ketamine Treatment Study. Neuropsychopharmacology. 2018 Apr 5. doi: 10.1038/s41386-018-0057-1. [Epub ahead of pri — View Citation
Evans JW, Szczepanik J, Brutsché N, Park LT, Nugent AC, Zarate CA Jr. Default Mode Connectivity in Major Depressive Disorder Measured Up to 10 Days After Ketamine Administration. Biol Psychiatry. 2018 Oct 15;84(8):582-590. doi: 10.1016/j.biopsych.2018.01. — View Citation
Gilbert JR, Yarrington JS, Wills KE, Nugent AC, Zarate CA Jr. Glutamatergic Signaling Drives Ketamine-Mediated Response in Depression: Evidence from Dynamic Causal Modeling. Int J Neuropsychopharmacol. 2018 Apr 13. doi: 10.1093/ijnp/pyy041. [Epub ahead of — View Citation
Kadriu B, Gold PW, Luckenbaugh DA, Lener MS, Ballard ED, Niciu MJ, Henter ID, Park LT, De Sousa RT, Yuan P, Machado-Vieira R, Zarate CA. Acute ketamine administration corrects abnormal inflammatory bone markers in major depressive disorder. Mol Psychiatry — View Citation
Nugent AC, Ballard ED, Gould TD, Park LT, Moaddel R, Brutsche NE, Zarate CA Jr. Ketamine has distinct electrophysiological and behavioral effects in depressed and healthy subjects. Mol Psychiatry. 2018 Feb 27. doi: 10.1038/s41380-018-0028-2. [Epub ahead o — View Citation
Nugent AC, Zarate CA Jr. Using Neuroimaging to Decipher the Mechanism of Action of Ketamine: A Pathway to Novel Therapeutics? Biol Psychiatry Cogn Neurosci Neuroimaging. 2017 Oct;2(7):549-551. doi: 10.1016/j.bpsc.2017.08.006. Epub 2017 Oct 5. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | MADRS Score - 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. | Baseline | |
Primary | MADRS Score - Day 1 Following Intervention | 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. | Day 1 |
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