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Ketamine Plus Lithium in Treatment-Resistant Depression

Information source: Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Depression

Intervention: Ketamine and Lithium (Drug); Ketamine and Placebo (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Icahn School of Medicine at Mount Sinai

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

Overall contact:
Jaclyn Schwartz, Phone: 212-241-3116, Email: jaclyn.schwartz@mssm.edu

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.

Clinical Details

Official title: Ketamine Plus Lithium as a Novel Pharmacotherapeutic Strategy in Treatment-Resistant Depression

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

Primary outcome: Montgomery Asberg Depression Rating Scale

Secondary outcome:

Quick Inventory of Depressive Symptoms

Patient Rated Inventory of Side Effects (PRISE)

Clinical Global Impression

Hamilton Psychiatric Rating Scale for Anxiety (HAM-A)

Detailed description: Major Depressive Disorder (MDD) is a disabling medical illness and current monoaminergic treatments are slow to act and possess only limited efficacy. In this context, the discovery that the glutamate NMDA receptor antagonist ketamine is rapidly antidepressant (onset of

action within hours) - - even in patients suffering from treatment-resistant depression (TRD)

- - has ignited tremendous enthusiasm among clinicians, scientists and patients alike. A

critical obstacle to the translation of this discovery into a novel treatment, however, is the limited duration of action following a course of ketamine (e. g. 1-2 weeks). The current project will address this important gap in medical knowledge by testing a rational neuropharmacological strategy designed to optimize and sustain the rapid antidepressant effects of ketamine. Driven by the recent characterization of the molecular mechanisms underpinning the antidepressant and neuroplasticity effects of ketamine, we will test the combination of ketamine plus lithium in patients with TRD using a randomized, double blind, placebo-controlled design. The primary aims of the project are (1) to test the efficacy of lithium-plus-ketamine compared to placebo-plus-ketamine as an antidepressant combination strategy in TRD and (2) to gather data on the safety and tolerability of the lithium-plus-ketamine.

Eligibility

Minimum age: 21 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- 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. 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 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;

- 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.

Locations and Contacts

Jaclyn Schwartz, Phone: 212-241-3116, Email: jaclyn.schwartz@mssm.edu

Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States; Recruiting
Jaclyn Schwartz, Phone: 212-241-3116, Email: jacklyn.schwartz@mssm.edu
Dan Iosifescu, MD, Phone: 212-241-4480, Email: dan.iosifescu@mssm.edu
James W Murrough, Principal Investigator
Additional Information

Mood and Anxiety Disorders Program

Related 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. 2013 Aug 15;74(4):250-6. doi: 10.1016/j.biopsych.2012.06.022. Epub 2012 Jul 27.

Starting date: July 2013
Last updated: April 2, 2015

Page last updated: August 23, 2015

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