Low-Dose Naltrexone for Depression Relapse and Recurrence | RxWiki

Low-Dose Naltrexone for Depression Relapse and Recurrence

Overview[ - collapse ][ - ]

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	Major Depressive Disorder Depression, Unipolar Recurrence Relapse
Intervention	Drug: Naltrexone Drug: Placebo capsule
Phase	Phase 2
Sponsor	Massachusetts General Hospital
Responsible Party	Massachusetts General Hospital
ClinicalTrials.gov Identifier	NCT01874951
First Received	May 20, 2013
Last Updated	April 1, 2014
Last verified	April 2014

Tracking Information[ + expand ][ + ]

First Received Date	May 20, 2013
Last Updated Date	April 1, 2014
Start Date	June 2013
Estimated Primary Completion Date	June 2015
Current 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
Current Secondary Outcome Measures	SDS Total Score [Time Frame: Change from baseline to week 6] [Designated as safety issue: No]Sheehan Disability Scale (SDS)

Descriptive Information[ + expand ][ + ]

Brief Title	Low-Dose Naltrexone for Depression Relapse and Recurrence
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
Brief Summary	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.
Detailed Description	Not Provided
Study Type	Interventional
Study Phase	Phase 2
Study Design	Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Condition	Major Depressive Disorder Depression, Unipolar Recurrence Relapse
Intervention	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
Study Arm (s)	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. Active Comparator: Naltrexone-Naltrexone In this arm, patients will receive active naltrexone for all six weeks of the study.

Recruitment Information[ + expand ][ + ]

Recruitment Status	Recruiting
Estimated Enrollment	36
Estimated Completion Date	June 2015
Estimated Primary Completion Date	June 2015
Eligibility 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.
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Contact: David Mischoulon, M.D. 617-724-5198 dmischoulon@partners.org
Location Countries	United States

Administrative Information[ + expand ][ + ]

NCT Number	NCT01874951
Other Study ID Numbers	2013P000371
Has Data Monitoring Committee	No
Information Provided By	Massachusetts General Hospital
Study Sponsor	Massachusetts General Hospital
Collaborators	Not Provided
Investigators	Principal Investigator: David Mischoulon, M.D. Massachusetts General Hospital
Verification Date	April 2014

Locations[ + expand ][ + ]

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