Ketamine Plus Lithium in Treatment-Resistant Depression

NCT01880593 | Completed Phase 2 Results DMC

• 1 other identifier: GCO 13-0365
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

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. An additional purpose of this study is to research the effects of ketamine on brain function. You may qualify to take part in this research study because you have been diagnosed with major depressive disorder (MDD) and have not responded to past treatments.

Conditions

Depression

Keywords

Ketamine; glutamate; N-methyl-D-aspartate; depression; major depressive disorder; treatment resistant; antidepressant; lithium

Outcome Measures

Primary Outcomes (1)

• MADRS-S Score

  The Montgomery Asberg Depression Rating Scale (MADRS-S) has 10-items which are based on mood symptoms over the past 7 days. Each items is scored 0 (normal) to 6 (severe depression) with overall score ranges from 0 (normal) to 60 (severe depression).

  2 weeks after last ketamine infusion

Secondary Outcomes (6)

• QIDS-SR Score

  2 weeks after last ketamine infusion

• CGI-S Score

  2 weeks after last ketamine infusion

• HAM-A Score

  2 weeks after last ketamine infusion

• BSS Score

  2 weeks after last ketamine infusion

• CSSRS Score

  2 weeks after last ketamine infusion

Study Arms (2)

Ketamine and Lithium

EXPERIMENTAL

Subjects in this arm take 600-1200mg of Lithium pills at night for duration of the study

Drug: Lithium; Drug: Ketamine

Ketamine and Placebo

PLACEBO COMPARATOR

Subjects in this arm take placebo pills at night for duration of the study.

Drug: Ketamine; Drug: Placebo

Interventions

Lithium DRUG

Subjects in this arm take 600-1200mg of Lithium pills at night for duration of the study.

Also known as: Lithium Carbonate Immediate Release

Ketamine and Lithium

Ketamine DRUG

Ketamine and Lithium; Ketamine and Placebo

Placebo DRUG

Subjects in this arm take placebo pills at night for duration of the study.

Ketamine and Placebo

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients, 21-65 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);
• Current Major Depressive Episode of at least moderate severity, defined as a QIDS-SR score ≥ 14 and a CGI-S score of ≥ 4;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.

You may not qualify if:

• 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 within 2 weeks prior to randomization or fluoxetine within 4 weeks prior to randomization;
• Treatment with other antidepressants within one week of 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;

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Related Publications (1)

• 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.

  PMID: 22840761 BACKGROUND

MeSH Terms

Conditions

Depression; Depressive Disorder, Major

Interventions

Lithium; Lithium Carbonate; Ketamine

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Metals, Alkali; Elements; Inorganic Chemicals; Metals, Light; Metals; Carbonates; Alkalies; Carbonic Acid; Carbon Compounds, Inorganic; Lithium Compounds; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Dr. James Murrough
• Organization: Icahn School of Medicine at Mount Sinai

james.murrough@mssm.edu

212-241-7574

Study Officials

• James W Murrough, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: June 14, 2013
• First Posted: June 19, 2013
• Study Start: July 1, 2013
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: July 31, 2018
• Results First Posted: July 31, 2018

Record last verified: 2018-07

Locations

US (1)