Study of Naltrexone-Induced Blockade of Antidepressant Effects
Condition: Depression; Major Depressive Disorder
MeSH terms: Depressive Disorder; Depressive Disorder, Major
Intervention: Naltrexone 50 Mg Oral Tablet; Placebo oral tablet
Intervention description: Naltrexone hydrochloride (ReVia®. Toronto, ON: Teva Canada Limited; 2015) (onset of action: ≥15 minutes; peak effect: ~1 hour; duration: ~24 hours).; Placebo tablet that has no inherent power to produce an effect. In the inert pill condition, participants will receive an oral placebo tablet.
Intervention MeSH terms: Naltrexone
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: This is a pharmaco-fMRI study of one single dose of naltrexone or placebo followed by an fMRI session in a crossover design.
Masking: Double (Participant, Investigator)
Masking description: Double-blinded
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No

Summary:

      The goal of this study is to determine whether antidepressant placebo effects and contextual
      cues broadly, can be blocked by one single dose of the µ-opioid antagonist naltrexone. To
      test this hypothesis, un-medicated, patients with MDD completed a randomized, double-blind,
      placebo-controlled, cross-over study of 50mg of the µ-opioid antagonist naltrexone or
      matching placebo, immediately before a Pharmaco-fMRI scanning session.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adults, age 18-55 years; fluent in English and with the capacity to understand the
             nature of the study and sign the written informed consent since the research
             instruments used in this study are not available in other languages;

          -  Written informed consent obtained;

          -  Outpatients with a current primary diagnosis of nonpsychotic Major Depressive Disorder
             (MDD) per the Mini-International Neuropsychiatric Interview (M.I.N.I) with or without
             certain anxiety disorders (e.g., generalized anxiety, panic, agoraphobia, social
             phobia, and specific phobia); HDRS-17 score of ≥ 16 at Screening Visit;

          -  No more than one failed antidepressant trial of adequate dose and duration, as defined
             by the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire
             (MGH-ATRQ);

          -  Participants will need to be antidepressant medication-free for at least 21 days prior
             to the collection of imaging data (five weeks for fluoxetine). However, individuals
             currently taking antidepressants will not be eligible to enroll in the study, even if
             they are willing to stop their medications.

        Exclusion Criteria:

          -  Currently taking opioid analgesics or in acute opioid withdraw.

          -  Pregnant or breastfeeding or plan to become pregnant over the duration of the study;

          -  History (lifetime) of psychotic depressive, schizophrenic, bipolar (I, II, or NOS),
             schizoaffective, or other Axis I psychotic disorders;

          -  Meeting M.I.N.I. criteria for substance dependence in the last 6 months, except for
             nicotine, or substance abuse in the last 2 months;

          -  Requiring immediate hospitalization for psychiatric disorder or have an unstable
             general medical condition (GMC) that will likely require hospitalization or to be
             deemed terminal (life expectancy < 6 months after study entry);

          -  Requiring medications for their GMCs that contraindicate treatment with naltrexone;

          -  Having epilepsy or other conditions requiring an anticonvulsant;

          -  Receiving or have received during the current episode vagus nerve stimulation, ECT, or
             rTMS.

          -  Currently taking any psychiatric medication or other potential augmenting agents
             (e.g., T3 in the absence of thyroid disease, lithium, buspirone); Taking thyroid
             medication for hypothyroidism may be included only if they have been stable on the
             thyroid medication for 3 months;

          -  Receiving therapy that is depression specific, such as CBT or Interpersonal
             Psychotherapy of Depression (participants can participate if they are receiving
             psychotherapy that is not targeting the symptoms of depression, such as supportive
             therapy, marital therapy);

          -  Currently actively suicidal or considered a high suicide risk;

          -  Currently enrolled in another study, and participation in that study contraindicates
             participation in this study;

          -  Any reason not listed herein yet, determined by the site PI and research staff that
             makes participation in the study hazardous.

          -  Having any contraindication for the performance of an MRI, such as: the presence of
             metal implants or foreign metallic objects (e.g., braces or extensive dental work),
             severe claustrophobia, or inability to tolerate the scanning procedures.