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

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.
• 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 ( 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.

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.