Does Naltrexone cause depression?


By Arnab Datta, MD 
Published on Feb 29, 2024

Here’s some information on whether Naltrexone causes depression. I don’t believe that it does. But there are some nuances around it.

Naltrexone is a mu opiate receptor blocker. It’s not a controlled-substance medication. There are overlaps between the dopamine and norepinephrine circuitry and the brain, which still remains largely undiscovered. These tracts were my focus while I was in the neuroscience lab during my postdoc at Albert Einstein College of Medicine in Bronx, New York. Some patients have reported something they perceive as depression. Here’s where I think it comes from:

Say somebody is drinking alcohol. Drinking alcohol releases endorphins and increases dopamine, norepinephrine, and even opiates circulating in the intrasynaptic space in the brain. Making them feel euphoric. It’s because of this euphoria that a lot of patients want to drink more alcohol or use the drug again. Either the drug lifts them up and makes them feel really high; that’s a good feeling for patients or the drug makes them stoned and really chilled out, which also makes them feel good. This is the reinforcing factor of these drugs. As a result, when you have a new opiate receptor blocker, you are naturally going to dampen these feelings of getting high or stoned. That’s why these patients sometimes say that they’re feeling depressed. 

Drug addiction and behavioral addiction have messed up the receptor morphology of these patients. And there’s no easy way to treat or cure behavioral or drug addiction. It’s going to be hard, no matter which way you approach it. That’s why, when I treat these patients, there’s always an element of psychotherapy. I get into their emotions and try to ascertain in what way they’re feeling depressed. They’re going to feel something different because they’re not on the drug anymore or because they’re trying to reduce the drug or behavior that used to make them feel a certain way that they liked. 

Clinical depression is a different thing. Clinical depression is marked by anhedonia. People will not enjoy doing what they used to really like to do. Somebody who really liked going out or singing might not want to do that anymore due to their depression. It’s hopelessness and helplessness that unfortunately dawn on the patient; it might be due to life stressors, or it might be due to a number of things. When patients take Naltrexone, they might not want to do the drug or behavior that they enjoy, but that’s a good thing. That’s what we’re trying to achieve. So it’s a really nuanced overlap.

In the end, it’s a risk-benefit ratio that we have to consider for each medication. I personally would rather have the patients not take the negative behavior or the bad drug. It’s going to cause some mood ups and downs, no matter how you look at it. That’s why psychotherapy is so integral to this whole process.

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