Continuation Ketamine in Major Depression

Condition(s) targeted: Major Depressive Disorder

Intervention: Lithium (Drug); Ketamine (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: James Murrough

Official(s) and/or principal investigator(s):
James W Murrough, MD, Principal Investigator, Affiliation: Icahn School of Medicine at Mount Sinai

As of May 21st, 2012, the purpose of this study is to test the antidepressant effect of ketamine when given repeatedly over a period of 1 week, as well as the use of Lithium as a relapse-prevention strategy for patients with treatment-resistant depression (TRD) who respond to an initial series of ketamine infusions. Ketamine is a Food and Drug Administration approved anesthetic (a drug used to produce loss of consciousness before and during surgery). Ketamine is not approved for the treatment of major depressive disorder and is considered experimental in this study.

Official title: Continuation Intravenous Ketamine in Major Depressive Disorder - Modification: Lithium for Relapse Prevention

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Montgomery Asberg Depression Rating Scale

Secondary outcome:

Hamilton Anxiety Rating Scale

Quick Inventory of Depressive Symptoms

Systematic Assessment for Treatment Emergent Events (SAFT)

Clinical Global Impression

Minimum age: 21 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Male or female patients, 21-80 years of age;

- Female individuals who are not of childbearing potential (i. e., surgically sterile,

postmenopausal for at least one year) or using a medically accepted reliable means of contraception. Women using oral contraceptive medication for birth control must also be using a barrier contraceptive. Women of childbearing potential must also have a negative serum B-HCG at screening and at pre-infusion;

- Participants must fulfill DSM-IV criteria for Major Depression without psychotic

features, based on clinical assessment by a study psychiatrist and confirmed by a structured diagnostic interview, the Structured Clinical Interview for DSM-IV TR Axis I Disorders, Patient Edition (SCID-P);

- Participants must have a history of at least one previous episode of depression prior

to the current episode (recurrent MDD) or have chronic MDD (of at least two years' duration);

- Participants have not responded to two or more adequate trials of an antidepressant

as determined by Antidepressant Treatment History Form (ATHF) criteria (score >=3);

- Participant scores on the IDS-C30 must be greater than or equal to 32;

- Current major depressive episode is of at least 4 weeks duration;

- Each participant must have a level of understanding sufficient to agree to all tests

and examinations required by the protocol and must sign an informed consent document;

- Each participant must be able to identify a family member, physician, or friend who

will participate in the Treatment Contract. Exclusion Criteria:

- Lifetime history of psychotic features, diagnosis of schizophrenia or any other

psychotic disorder, or diagnosis of bipolar disorder;

- Lifetime histories of autism, mental retardation, pervasive developmental disorders,

or Tourette's syndrome;

- Current diagnosis of OCD or eating disorder (bulimia nervosa or anorexia nervosa);

- Subjects with DSM-IV drug or alcohol abuse/dependence within the preceding 2 years;

- Patients with schizotypal or antisocial personality disorder, or any clinically

significant axis II disorder that would, in the investigator's judgment, preclude safe study participation;

- Patients judged clinically to be at serious and imminent suicidal or homicidal risk;

- Women who are either pregnant or nursing;

- Serious, unstable medical illnesses including hepatic, renal impairment,

gastroenterologic (including gastro-esophageal reflux disease), respiratory (including obstructive sleep apnea, or history of difficulty with airway management during previous anesthetics), cardiovascular (including ischemic heart disease and uncontrolled hypertension), endocrinologic, neurologic (including history of severe head injury), immunologic, or hematologic disease;

- Clinically significant abnormal findings of laboratory parameters, physical

examination, or ECG;

- Patients who have a positive urine toxicology for illicit substances at screening and

within 24 hours of the infusion;

- Patients with one or more seizures without a clear and resolved etiology;

- Treatment with an irreversible MAOI or any other psychotropic medication within 2

weeks prior to randomization (with the exception of a stable dose of non-benzodiazepines hypnotics);

- Treatment with fluoxetine within 4 weeks prior to randomization;

- Previous recreational use of PCP or ketamine;

- Hypertension (systolic BP >160 mm Hg or diastolic BP >90 mm Hg) not controlled by

diuretic or beta-blocker therapy alone or in combination;

- A blood pressure reading over 160/90 or two separate readings over 140/90 at

screening or baseline visits;

- Renal impairment, as reflected by a BUN > 20 mg/dL and/or creatinin clearance of

>1. 3 mg/dL;

- Thyroid impairment, as reflected by a TSH > 4. 2 mU/L;

- Cardiac disease, as reflected by an EKG that is abnormal and of concern for cardiac

disease;

- Any anticipated change in medications that could affect fluid or salt balance,

including the following antihypertensive agents: ACE inhibitor, loop diuretics, calcium channel blockers, thiazide diuretics, angiotensin II receptor blockers.

Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States

Related publications:

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.

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.

Murrough JW, Perez AM, Pillemer S, Stern J, Parides MK, aan het Rot M, Collins KA, Mathew SJ, Charney DS, Iosifescu DV. Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression. Biol Psychiatry. 2013 Aug 15;74(4):250-6. doi: 10.1016/j.biopsych.2012.06.022. Epub 2012 Jul 27.

Starting date: October 2007
Last updated: May 22, 2014