Low-Dose Naltrexone (LDN) for Depression Relapse and Recurrence

NCT01874951 | Completed Phase 2 Results

• 1 other identifier: 2013P000371
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Major Depressive Disorder; Depression, Unipolar; Recurrence; Relapse

Keywords

Depression; Recurrence; Relapse; Antidepressants; Naltrexone; Drug augmentation

Outcome Measures

Primary Outcomes (1)

• Change in HAM-D-17 Total Score

  Hamilton Depression Scale-17 (HAM-D-17) item. The change in scores depends on the difference between the initial (baseline) score and the final score at the conclusion of the double blind treatment period. There is no formal range of score changes, since they depend on the initial and final score. A negative score represents a lowering in the score from baseline to end (improvement), and a positive score indicates an increase in score from baseline to end (worsening). A zero score would indicate no change. In theory, the maximum drop in score would be from 52 to zero, or -52. A maximum increase would be from 18 (the minimum score required for admission) to 52, or +34.

  Change from baseline to week 3

Secondary Outcomes (7)

• Change in HAM-D28 Total Score

  Change from baseline to week 3

• Change in MADRS-10 Total Score

  Change from baseline to week 3

• Change in MADRS-15 Total Score

  Change from baseline to week 3

• Change in CGI-S Total Score

  Change from baseline to week 3

• Final CGI-I Score

  From baseline to week 3

Study Arms (2)

Placebo

PLACEBO COMPARATOR

In this arm, patients will receive placebo for three weeks.

Drug: Placebo

Naltrexone

EXPERIMENTAL

In this arm, patients will receive low dose naltrexone for three weeks.

Drug: Naltrexone

Interventions

Naltrexone DRUG

1 mg of naltrexone will be given twice daily to all patients assigned to active drug.

Also known as: LDN

Naltrexone

Placebo DRUG

Placebo identical in appearance to naltrexone will be given twice daily to all patients assigned to placebo.

Placebo

Eligibility Criteria

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

You may qualify if:

• Age 18-65.
• Written informed consent.
• Meet Diagnostic and Statistical Manual (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 American College of Neuropsychopharmacology (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.
• Dopaminergic agents here include classical stimulants from the amphetamine or methylphenidate families; dopamine agonists (e.g. pramipexole); or dopamine active antidepressants like bupropion.
• 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.
• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Boston Clinical Trials: collaborator

Study Sites (1)

Massachusetts General Hospital; Depression Research and Clinical Program

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• Mischoulon D, Hylek L, Yeung AS, Clain AJ, Baer L, Cusin C, Ionescu DF, Alpert JE, Soskin DP, Fava M. Randomized, proof-of-concept trial of low dose naltrexone for patients with breakthrough symptoms of major depressive disorder on antidepressants. J Affect Disord. 2017 Jan 15;208:6-14. doi: 10.1016/j.jad.2016.08.029. Epub 2016 Oct 1.

  PMID: 27736689 RESULT

MeSH Terms

Conditions

Depressive Disorder, Major; Depressive Disorder; Recurrence; Depression

Interventions

Naltrexone

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Limitations and Caveats

1\) Very small sample. 2) No detailed data about the total number of relapses or recurrences prior to the patients' current regimen. 3) Short double blind treatment period. 4) Focus on antidepressants with dopaminergic activity only.

Results Point of Contact

• Title: David Mischoulon, MD, PhD, Director of Research
• Organization: Depression Clinical and Research Program, Massachusetts General Hospital

dmischoulon@partners.org

617-724-5198

Study Officials

• David Mischoulon, M.D.

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Psychiatrist

Study Record Dates

• First Submitted: May 20, 2013
• First Posted: June 11, 2013
• Study Start: June 1, 2013
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: February 24, 2017
• Results First Posted: February 24, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)