Protocol Number: 04-M-0222

Title:

Investigation of the Rapid (Next Day) Antidepressant Effects of an NMDA Antagonist

Number:

04-M-0222

Summary:

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 60 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.

Sponsoring Institute:

National Institute of Mental Health (NIMH)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

1. Male or female subjects, 18 to 60 years of age.

2. Female subjects of childbearing potential must be using a medically accepted means of contraception.

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

4. Subjects must fulfill DSM-IV criteria for Major Depression (296.3) without psychotic features, based on clinical assessment and confirmed by a structured diagnostic interview, SCID-P.

5. Subjects must have an initial score of at least 18 on the 21-item HDRS at screen and at baseline of study phase I.

6. Current or past history of lack of response to two adequate antidepressant trials (may be from the same chemical class) operationally defined using the Antidepressant Treatment History Form (ATHF).

7. Current major depressive episode of at least 4 weeks duration.

EXCLUSION CRITERIA:

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

9. Subjects with a history of DSM-IV drug or alcohol dependency or abuse (including for nicotine) within the preceding 3 months.

10. Female subjects who are either pregnant or nursing.

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

12. Subjects with uncorrected hypothyroidism or hyperthyroidism.

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

14. Previous treatment with ketamine or hypersensitivity to amantadine.

15. Treatment with a reversible MAOI within 4 weeks prior to study phase I.

16. Treatment with fluoxetine within 5 weeks prior to study phase I.

17. Treatment with any other concomitant medication not allowed (Appendix A) 14 days prior to study phase I.

18. Treatment with clozapine or ECT within 3 months prior to study phase I.

19. Judged clinically to be at serious suicidal risk.

No structured psychotherapy will be permitted during the study.

Special Instructions: Currently Not Provided

Keywords:

Depression

NMDA Antagonist

Treatment Resistant

Glutamatergic System

Ketamine

Recruitment Keywords:

Depression

Major Depression

Conditions:

Depression

Investigational Drug(s):

None

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Agnoli A, Ruggieri S, Casacchia M.

Restatement and prospectives of ergot alkaloids in clinical neurology and psychiatry.

Pharmacology. 1978;16 Suppl 1:174-88. No abstract available.

PMID: 347463

Agren H, Mefford IN, Rudorfer MV, Linnoila M, Potter WZ.

Interacting neurotransmitter systems. A non-experimental approach to the 5HIAA-HVA correlation in human CSF.

J Psychiatr Res. 1986;20(3):175-93.

PMID: 2430098

Anderson IM.

SSRIS versus tricyclic antidepressants in depressed inpatients: a meta-analysis of efficacy and tolerability.

Depress Anxiety. 1998;7 Suppl 1:11-7.

PMID: 9597346

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Networks and Applications, CC.

Search The Studies | Help | Questions |
Clinical Center Home | NIH Home

Warren Grant Magnuson Clinical Center (CC)
National Institutes of Health (NIH)
Bethesda, Maryland 20892. Last update: 10/15/2004