Low-Dose Naltrexone for Depression




Naltrexone is used in 50- 100 mg daily dose for opioid use disorder treatment. 

LDN is 1/10th of this typical opioid use disorder treatment dose = MEAN OF 4.5MG DAILY DOSE.




  • Naltrexone at low dose exhibits anti-inflammatory and analgesic property

  • LDN —> increase in BDNF.

  • Proposed dopaminergic mechanism of low-dose naltrexone.


Role of LDN for patients with breakthrough symptoms of major depressive disorder on antidepressants:


This randomized, proof-of-concept trial will answer this question:

N= 12 adults.

Diagnosis: recurrent DSM-IV major depressive disorder (MDD) on dopaminergic antidepressant regimens:

  • Stimulants

  • Dopamine agonists

  • Bupropion [≥300mg/day]

  • Aripiprazole [≤2.5mg/day] or

  • Sertraline [≥150mg/day])

Patient’s were randomized to naltrexone 1mg b.i.d. (n=6) or placebo (n=6) augmentation for 3 weeks.



(A) Hamilton Depression Rating Scale (HAM-D-17) scores:

  • for LDN: decreased from 21.2±2.0 to 11.7±7.7.

  • for Placebo: decreased from 23.7±2.3 to 17.8±5.9.

(B) HAM-D-28 scores:

  • for LDN: decreased from 26.2±4.0 to 12.0±9.8.

  • for Placebo: decreased from 26.3±2.6 to 19.8±6.6.

(C) Montgomery-Asberg Depression Rating Scale (MADRS-10 item) scores:

  • for LDN: decreased from 30.4±4.9 to 12.2±8.4.

  • for Placebo: decreased from 30.7±4.3 to 22.8±8.5).

(D) MADRS-15 item scores:

  • for LDN: decreased from 36.6±6.2 to 13.2±8.8.

  • for Placebo: decreased from 36.7±4.2 to 26.0±10.0.

(E) Clinical Global Improvement Scale-Severity (CGI-S) scores:

  • for LDN: decreased from 4.3±0.5 to 3.0±1.1.

  • for Placebo: decreased from 4.3±0.5 to 4.0±0.6.


  1. Clin Rheumatol. 2014; 33(4): 451–459.
  2. J Affect Disord. 2017 Jan 15;208:6-14.


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Dr. Harvinder Singh, M.D. (Admin)

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