Low-Dose Naltrexone for Depression Relapse and Recurrence

Major Depressive Disorder Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01874951
• Other study ID #: 2013P000371
• Status: Completed
• Phase: Phase 2
• First received: May 20, 2013
• Last updated: July 1, 2015
• Start date: June 2013
• Est. completion date: June 2015

Study information

• Verified date: July 2015
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Depression, Unipolar
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder
• 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.
• Placebo capsule

Locations

Country	Name	City	State
United States	Massachusetts General Hospital; Depression Research and Clinical Program	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HAM-D-17 Total Score	17-item Hamilton Rating Scale for Depression	Change from baseline to week 6	No
Secondary	SDS Total Score	Sheehan Disability Scale (SDS)	Change from baseline to week 6	No