Ketamine Frequency Treatment for Major Depressive Disorder

Condition(s) targeted: Treatment Resistant Depression

Intervention: Ketamine (Drug)

Phase: Phase 4

Status: Enrolling by invitation

Sponsored by: St. Mary's Duluth Clinic Health System

Official(s) and/or principal investigator(s):
Micheal Messer, MD, Principal Investigator, Affiliation: St. Mary's Duluth Clinic Health System

Depression is a wide spread illness. Depression contributes most significantly to national health care costs. While the number and types of treatments used for depression have expanded over the years, even with an increased range of options, the response rate, defined as the number of subjects who have a 50% reduction in depressive symptoms, is estimated to be around 65%.

In this pilot study we will assess the feasibility of conducting a randomized clinical trial that will examine the frequency of treatment with ketamine in patients with TDR without psychosis. It will compare two modes of the ketamine treatment; every other day ketamine, versus two active and four placebo treatments over the period of 12 days.

Official title: Ketamine Frequency Treatment for Major Depressive Disorder

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Dose Comparison, Single Group Assignment, Efficacy Study

Primary outcome: The primary efficacy measure is the change in scores in the 21-item Hamilton Depression Rating Scale.

Secondary outcome: · Proportion of patients with remission (HDRS score < 18) at the end of the 2-week treatment and each follow-up contact.

Minimum age: 30 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Age 30 to 65

- Major depressive disorder without psychotic features confirmed by a structured

clinical diagnostic interview, SCID.

- Treatment resistant depression defined using the Antidepressant Treatment History Form

(ATHF)

- HDRS 21 score > 18

- Female participants of childbearing potential must be using a medically accepted means

of contraception (birth control pills, spermicidal barrier)

- Ability to concur with medication standardization regiment (section as an outpatient

- Physically healthy (no chronic diseases; normal CBC, BMP, AST, ALT, and UA)

- Competent to give informed consent to all required tests and examinations and sign a

consent document

Exclusion Criteria:

- Bipolar disorder

- Psychosis or any other psychotic disorder as defined by DSM-IV criteria

- Serious or imminent threat for suicide

- Pregnant or nursing female

- Presence of serious unstable medical illnesses including hepatic, renal,

gastrointestinal, respiratory, cardiovascular, endocrinologic, neurologic, immunologic, or hematologic disease, or abnormal laboratory tests (CBC, BMP, AST, ALT, and UA)

- Uncontrolled hypertension

- History of CVA

- Treatment with St. Johns wort, tramadol, phentolamine, naloxone, or anticholinergic

medications

- Alcohol or illicit drug abuse for 6 months (evidence from UDS)

- Currently involved in a clinical trial or used an experimental medication within the

last 30 days

- Hypersensitivity to ketamine products

St. Mary's Duluth Clinic Health System, Duluth, Minnesota 55805, United States

Related publications:

Pincus HA, Pettit AR. The societal costs of chronic major depression. J Clin Psychiatry. 2001;62 Suppl 6:5-9. Review.

Burrows GD, Norman TR, Judd FK. Definition and differential diagnosis of treatment-resistant depression. Int Clin Psychopharmacol. 1994 Jun;9 Suppl 2:5-10. Review.

Crown WH, Finkelstein S, Berndt ER, Ling D, Poret AW, Rush AJ, Russell JM. The impact of treatment-resistant depression on health care utilization and costs. J Clin Psychiatry. 2002 Nov;63(11):963-71.

Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000 Feb 15;47(4):351-4.

Correll GE, Futter GE. Two case studies of patients with major depressive disorder given low-dose (subanesthetic) ketamine infusions. Pain Med. 2006 Jan-Feb;7(1):92-5. No abstract available.

Kudoh A, Takahira Y, Katagai H, Takazawa T. Small-dose ketamine improves the postoperative state of depressed patients. Anesth Analg. 2002 Jul;95(1):114-8, table of contents.

Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006 Aug;63(8):856-64.

Hirota K, Lambert DG. Ketamine: its mechanism(s) of action and unusual clinical uses. Br J Anaesth. 1996 Oct;77(4):441-4. No abstract available.

Paul IA, Skolnick P. Glutamate and depression: clinical and preclinical studies. Ann N Y Acad Sci. 2003 Nov;1003:250-72. Review.

Annetta MG, Iemma D, Garisto C, Tafani C, Proietti R. Ketamine: new indications for an old drug. Curr Drug Targets. 2005 Nov;6(7):789-94. Review.

Stewart CE. Ketamine as a street drug. Emerg Med Serv. 2001 Nov;30(11):30, 32, 34 passim. Review.

Correll GE, Maleki J, Gracely EJ, Muir JJ, Harbut RE. Subanesthetic ketamine infusion therapy: a retrospective analysis of a novel therapeutic approach to complex regional pain syndrome. Pain Med. 2004 Sep;5(3):263-75.

Bremner JD, Krystal JH, Putnam FW, Southwick SM, Marmar C, Charney DS, Mazure CM. Measurement of dissociative states with the Clinician-Administered Dissociative States Scale (CADSS). J Trauma Stress. 1998 Jan;11(1):125-36.

Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. Feb 1960;23:56-62.

Starting date: March 2008
Ending date: August 2008
Last updated: March 27, 2008