Low-Dose Naltrexone for Depression Relapse and Recurrence

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Massachusetts General Hospital
Sponsor:
Information provided by (Responsible Party):
David Mischoulon, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01874951
First received: May 20, 2013
Last updated: April 1, 2014
Last verified: April 2014
  Purpose

The purpose of this pilot study is to determine if taking a low dose of naltrexone in addition to an antidepressant medication can help treat relapse or recurrence in people with Major Depressive Disorder (MDD). The U.S. Food and Drug Administration (FDA) has approved naltrexone for the treatment of alcohol dependence and opioid dependence, but the FDA has not approved naltrexone to treat depression. The investigators hypothesize that patients with breakthrough depression on an antidepressant regimen containing a pro-dopaminergic agent assigned to treatment with low dose naltrexone will demonstrate higher rates of response compared to those patients taking placebo.


Condition Intervention Phase
Major Depressive Disorder
Depression, Unipolar
Recurrence
Relapse
Drug: Naltrexone
Drug: Placebo capsule
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized, Proof-Of-Concept Trial of Augmentation of Anti-depressants by Low Dose and Ultra-Low Dose Naltrexone for Patients With Breakthrough Symptoms of Major Depressive Disorder on Antidepressant Therapy

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • HAM-D-17 Total Score [ Time Frame: Change from baseline to week 6 ] [ Designated as safety issue: No ]
    17-item Hamilton Rating Scale for Depression


Secondary Outcome Measures:
  • SDS Total Score [ Time Frame: Change from baseline to week 6 ] [ Designated as safety issue: No ]
    Sheehan Disability Scale (SDS)


Estimated Enrollment: 36
Study Start Date: June 2013
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo-Naltrexone
In this arm, patients will receive placebo for the first three weeks of the study. All placebo non-responders will receive naltrexone during the final three weeks of the study.
Drug: Naltrexone
1 mg bid of naltrexone will be given to all patients regardless of study arm when they are receiving active drug.
Drug: Placebo capsule
Active Comparator: Naltrexone-Naltrexone
In this arm, patients will receive active naltrexone for all six weeks of the study.
Drug: Naltrexone
1 mg bid of naltrexone will be given to all patients regardless of study arm when they are receiving active drug.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18-65.
  • Written informed consent.
  • Meet DSM-IV criteria (by Structured Clinical Interview for DSM-IV SCID-I/P) for Major Depressive Disorder (MDD), current.
  • Quick Inventory of Depressive Symptomatology - Self-Rated (QIDS-SR) score of at least 12 at both screen and baseline visits.
  • Received treatment with either an Selective serotonin re-uptake inhibitors (SSRI) in combination with a dopaminergic agent, or with an antidepressant with a dopaminergic mechanism of action in adequate doses, achieved remission per ACNP Task Force guidelines for ≥3 months, currently in relapse or recurrence without dose change for at least the past 4 weeks, based on meeting DSM-IV criteria for MDD.

    1. Dopaminergic agents here include classical stimulants from the amphetamine or methylphenidate families; dopamine agonists (e.g. pramipexole); or dopamine active antidepressants like bupropion.
    2. Additionally, low dose (< 2.5 mg) Abilify, a D2 partial agonist, is believed to exert pro-dopaminergic effects and will therefore be included as a dopamine agent.
    3. Sertraline, although classified as an SSRI, has dopamine reuptake inhibiting properties believed to be relevant at higher doses (> 150 mg of sertraline), and will also therefore be considered a dopaminergic antidepressant at dose range above.
    4. Based on the finding that the norepinephrine transporter is the reuptake inhibitor for dopamine in the prefrontal cortex and the robust sustained clinical response of a patient on duloxetine and low dose naltrexone, we include duloxetine, traditionally classed as an SNRI, among the dopamine acting antidepressants.)
  • During the baseline visit, patients must be on a stable dose of antidepressant regimen for the past 4 weeks.

Exclusion Criteria:

  • Pregnant women or women of child bearing potential who are not using a medically accepted means of contraception (to include oral contraceptive or implant, condom, diaphragm, spermicide, intrauterine device, tubal ligation, or partner with vasectomy).
  • Patients who no longer meet DSM-IV criteria for MDD during the baseline visit.
  • Patients who demonstrate a greater than 25% decrease in depressive symptoms as reflected by the QIDS-SR total score - screen to baseline.
  • Serious suicide or homicide risk, as assessed by evaluating clinician.
  • Unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease.
  • Substance use disorders active within the last six months, any bipolar disorder (current or past), any psychotic disorder (current or past).
  • History of a seizure disorder or clinical evidence of untreated hypothyroidism.
  • Patients requiring excluded medications (including but not limited to chronic or episodic use of anorexiants, episodic hormones, episodic benzodiazepines, episodic insulin, episodic and other episodic psychotropic medications).
  • Psychotic features in the current episode or a history of psychotic features, as assessed by SCID.
  • History of naltrexone intolerance at any dose.
  • Patients with a history of antidepressant-induced hypomania.
  • Inadequate exposure time or dose of current SSRI or Serotonin-norepinephrine reuptake inhibitor (SNRI); failure to comply with at least 80% of doses.
  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: NCT01874951

Contacts
Contact: David Mischoulon, M.D. 617-724-5198 dmischoulon@partners.org

Locations
United States, Massachusetts
Massachusetts General Hospital; Depression Research and Clinical Program Recruiting
Boston, Massachusetts, United States, 02114
Contact: James Doorley, BA    617-724-3222    jdoorley@partners.org   
Principal Investigator: David Mischoulon, M.D.         
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: David Mischoulon, M.D. Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: David Mischoulon, MD, Staff Psychiatrist, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01874951     History of Changes
Other Study ID Numbers: 2013P000371
Study First Received: May 20, 2013
Last Updated: April 1, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
Depression
Recurrence
Relapse
Antidepressants
Naltrexone
Drug augmentation

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Disease
Recurrence
Behavioral Symptoms
Disease Attributes
Mental Disorders
Mood Disorders
Pathologic Processes
Antidepressive Agents
Naltrexone
Central Nervous System Agents
Narcotic Antagonists
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014