Low-Dose Naltrexone (LDN) for Depression Relapse and Recurrence
Condition: Major Depressive Disorder; Depression, Unipolar; Recurrence; Relapse
MeSH terms: Recurrence; Depression; Depressive Disorder; Depressive Disorder, Major
Intervention: Naltrexone; Placebo
Intervention description: 1 mg of naltrexone will be given twice daily to all patients assigned to active drug.; Placebo identical in appearance to naltrexone will be given twice daily to all patients assigned to placebo.
Intervention MeSH terms: Naltrexone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Depression; Recurrence; Relapse; Antidepressants; Naltrexone; Drug augmentation

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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.

               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.