Continuation Ketamine in Major Depression

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
James Murrough, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:
NCT00548964
First received: October 24, 2007
Last updated: May 22, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Major Depressive Disorder
Drug: Lithium
Drug: Ketamine
Phase 1

Study Type: Interventional
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
Official Title: Continuation Intravenous Ketamine in Major Depressive Disorder - Modification: Lithium for Relapse Prevention

Resource links provided by NLM:


Further study details as provided by Mount Sinai School of Medicine:

Primary Outcome Measures:
  • Montgomery Asberg Depression Rating Scale [ Time Frame: one week ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Hamilton Anxiety Rating Scale [ Time Frame: one week ] [ Designated as safety issue: No ]
  • Quick Inventory of Depressive Symptoms [ Time Frame: one week ] [ Designated as safety issue: No ]
  • Systematic Assessment for Treatment Emergent Events (SAFT) [ Time Frame: one week ] [ Designated as safety issue: Yes ]
  • Clinical Global Impression [ Time Frame: one week ] [ Designated as safety issue: No ]

Enrollment: 36
Study Start Date: October 2007
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ketamine + Lithium
All participants receive the study drug, IV ketamine, open-label
Drug: Lithium
600-900mg of Li carbonate
Other Name: Lithium Carbonate
Drug: Ketamine
0.5mg/kg of ketamine
Other Name: Intravenous ketamine hydrochloride
Active Comparator: Ketamine + Placebo
All participants receive the study drug, IV ketamine, open-label
Drug: Ketamine
0.5mg/kg of ketamine
Other Name: Intravenous ketamine hydrochloride

  Eligibility

Ages Eligible for Study:   21 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT00548964

Locations
United States, New York
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
Sponsors and Collaborators
James Murrough
Investigators
Principal Investigator: James W Murrough, MD Mount Sinai School of Medicine
  More Information

Publications:
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. 2012 Jul 26. [Epub ahead of print]

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: James Murrough, Principal Investigator, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier: NCT00548964     History of Changes
Other Study ID Numbers: 06-1225 (002)
Study First Received: October 24, 2007
Last Updated: May 22, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Mount Sinai School of Medicine:
Ketamine
glutamate
N-methyl-D-aspartate
treatment resistant
major depressive disorder
lithium

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

ClinicalTrials.gov processed this record on August 21, 2014