Naltrexone For Opioid Use Disorder and Alcohol Use Disorder

MOA: mu opioid receptor antagonist which prevents exogenous opioids from binding blocking the pleasurable effects of opioid use. Reduces alcohol consumption through modulation of the opioid system, blocking the reinforcing effects of alcohol. 

FDA Indications: alcohol use disorder (oral or injectable), Prevention of relapse to opioid dependence (injection)

Oral Dose: 50 mg/day 

Injection Dose: 380 mg/month 

Caution: patient must be opioid free for 7-10 days prior to starting, conformed with a negative urine 

For alcohol use disorder start with 50 mg/day or 380 mg/month for IM formulation (injection may be preferred because it eliminates the daily decision to take the medication) 

Side effects: nausea, vomiting, decreased appetite, dizziness, injection site reaction, life-threatening side effect is hepatocellular injury in overdose 

Who is it good for?: Those ready to abstain completely from alcohol and for binge drinkers. Good evidence for reducing heavy drinking days. There is some risk of apathy or loss of pleasure with chronic use. The combination of naltrexone and bupropion has been used as a treatment for obesity. 

Psychotropics: Acamprosate For Alcohol Use Disorder

I received a question asking me to discuss acamprosate as a medication and specifically to address any evidence to support its use to reduce urges to self-harm. I did the research, and this is what I found. 

Ketamine for Alcohol Use Disorder

In a previous post we discussed the details of Esketamine and the important things patients need to know about the medication. In this post I will discuss the experimental treatment for problematic drinking that involves a single infusion of ketamine. Now I know what you might be thinking. Here we go again, psychiatrists using a medication with potential for addiction on patients already struggling with addiction. It seems like we are just substituting on drug for another drug. Before we get too excited let’s look at the evidence. 

The study looked at 90 heavy drinkers, which all had a score greater than 8 on the Alcohol Use Disorder Identification Test but did not have a formal diagnosis of alcohol use disorder. Bottom line, the people in the study were drinking a lot but were not diagnosed with a use disorder. 

The study participants received a single dose of intravenous (IV) ketamine along with cognitive behavioral therapy (CBT) that focused on “maladaptive reward memories” (MRMs). The idea behind the combination of ketamine and CBT is that it works to reboot the brains reward pathway which has been overrun by excessive drinking. The ketamine infusion sets the stage for the CBT and allows the patient to relearn new more adaptive associations in relation to alcohol. In the study the combination of ketamine and CBT resulted in a 50% reduction in weekly alcohol consumption at 9 months. 

We know the reward system in the brain in suspectable to alterations and disordered function in the presence of substance use. Environmental triggers become associated with drug use, and these associations can be difficult to change. It’s essential to interrupt these reward memories and learn new healthy associations to prevent relapse. This is where the single ketamine infusion comes in. A promising method to break these associations is by interrupting the process of memory reconsolidation. These memories rely on N-methyl D-aspartate receptors (NMDAR) and ketamine acts as an antagonist (blocker) of these receptors. Theoretically ketamine should weaken the memories and make it easier to form new associations. Once the brain is susceptible to forming new associations the patient would be forming new associations with the help of the CBT protocol. Thus, the two therapies work in combination with each other. The ketamine acts as a primer setting the stage for new learning and the CBT helps to form new health associations.

My Take

I actually have some experience with the use of a single ketamine infusion in opioid use disorder along with transcranial magnetic stimulation, and a mindfulness-based CBT protocol. The concept was essential the same, just applied to opioid use disorder. I think treatments like this have potential. Clearly more studies are required before this treatment is available to larger patient populations. Alcohol remains a major cause of morbidity and mortality worldwide. We are looking for treatments that work and are going to enhance the lives of our patients. Time and more research will tell what impact this treatment has on addiction medicine, but it remains an exciting new approach. 

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