Naltrexone could alleviate depression symptoms in patients who relapsed while taking antidepressants

The drug naltrexone is approved for use in the treatment of opioid use disorders and alcohol use disorders, but preliminary research suggests it could also aid the treatment of depression.

The double-blind, randomized study found that low dose naltrexone reduced depression severity in 12 depressed subjects who had relapsed on dopamine-enhancing antidepressants. The study will be published in the January 2017 issue of the Journal of Affective Disorders.

PsyPost interviewed the study’s corresponding author, David Mischoulon of Massachusetts General Hospital/Harvard Medical School. Read his explanation of the research below:

PsyPost: Why were you interested in this topic?

Mischoulon: Our group studies a wide variety of treatments for depression. We are especially interested in the underlying biology of antidepressants and mechanisms by which depression develops. This study of low dose naltrexone (LDN) was based on a model proposed by Bear and Kessler, originally for restless leg syndrome for which it was patented. During treatment of patients with RLS, they observed anecdotally that LDN seemed to benefit depression as well.

Because one of the apparent mechanisms of low dose naltrexone is through dopamine, which is a neurotransmitter associated with mood regulation, Dr Bear’s company, PharmoRx, was interested in funding a pilot study on this agent for people with depression who had relapsed on dopaminergic antidepressants. They spoke with us about running such a study at MGH, and we agreed to do it.

What should the average person take away from your study?

The main finding is that if you have depression and relapsed while taking a previously effective antidepressant that works primarily by dopaminergic mechanisms, addition of LDN could potentially alleviate the depression in combination with the original antidepressant.

Are there any major caveats? What questions still need to be addressed?

The main limitation of this work is the small patient sample. We only treated 12 patients and this is too few to draw firm conclusions. We need to replicate this work in a larger group of patients. The study included only antidepressants that work by dopaminergic mechanisms, and so we don’t know how well it would work with other types of antidepressants, such as those that are primarily serotonergic (e.g. SSRIs) or noradrenergic (e.g. tricyclic antidepressants).

Also, LDN may involve a range of different doses that are defined as “low,” and so a dose-finding study to determine the optimal “low” dose would also be valuable to do. Clinicians who wish to prescribe LDN for depressive relapse should realize that this is considered an experimental therapy, and should inform their patients about the risks of trying a relatively unproven therapy.

Is there anything else you would like to add?

While LDN is obtainable by prescription from a licensed physician, it cannot be bought in most drugstores, because commercially available forms of naltrexone come in much higher doses. To obtain LDN you will need to take your prescription to a compounding pharmacy where they can prepare it for you in the appropriate dosage form. Most insurance plans will cover it, however, so LDN should be accessible to most people.

In addition to Mischoulon, the study “Randomized, proof-of-concept trial of low dose naltrexone for patients with breakthrough symptoms of major depressive disorder on antidepressants” was co-authored by Lindsay Hylek, Albert S. Yeung, Alisabet J. Clain, Lee Baer, Cristina Cusin, Dawn Flosnik Ionescu, Jonathan E. Alpert, David P. Soskin and Maurizio Fava.