Less than 8% of the 18 million people in the United States with alcohol use disorder receive any form of treatment, despite the availability of safe and effective medications. By the end of this video from our course, Essentials of Addiction Medicine, you'll know when to choose naltrexone, acamprosate, or disulfiram and what side effects to look out for.
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Having made it through acute detoxification, the greatest mistake that we make as clinicians is to neglect to discuss and initiate maintenance pharmacotherapy prior to discharge. As I alluded to in an earlier Medmastery lesson, imagine if we treated diabetic ketoacidosis in a patient with newly diagnosed diabetes, and then just sent them on their way, hoping for the best. If you learn nothing else during this lesson, I hope you'll at least feel obliged to initiate maintenance pharmacotherapy for alcohol use disorder. So, let's review the menu.
We're going to focus on the three options that have been approved by the United States Food and Drug Administration or FDA. These are naltrexone, acamprosate, and disulfiram. Note that there are also several non FDA approved options whose use is supported by a good deal of evidence. Naltrexone is a full opioid antagonist that was initially approved for opioid use disorder, but was later approved for alcohol use disorder as well. It has both a once daily oral form and a 30 day long acting injectable form.
Now, you may be wondering, what is an opioid antagonist doing here in the chapter on AUD. Well remember that while we often focus on GABA and glutamate systems when we're talking about alcohol withdrawal, alcohol also triggers the release of dopamine throughout the mesocortical limbic system, as well as endorphins from the pituitary and hypothalamus. It's the dopamine and endorphins that reinforce drinking behavior and make it pleasurable. So for a person who's feeling kind of blah, when they drink alcohol, those endorphins are released, and they feel better. But if that same person took some naltrexone own beforehand, it will block those endorphins from acting and you've essentially uncoupled drinking and it's pleasurable response.
Over time, the hope is that patients drink less alcohol, and ultimately lose interest in drinking. Studies show that this medication works. Indeed, there have been over 50 well controlled studies involving over 10,000 patients, confirming that this medication is safe, well tolerated and effective for curbing heavy drinking. By comparison, naltrexone is more effective at curbing heavy drinking, then statins are at preventing heart attacks, or heparin is at preventing blood clots. That's really effective.
Many patients and providers prefer the 30 day long acting injectable form over the oral one, since it essentially guarantees adherence for 30 days at a time. The injection, which is 4 milliliters is injected into the upper outer quadrant of the buttocks. Side effects include nausea, which tends to go away after a few days, headache, and for the injectable form a rare injection site reaction. As you might imagine, this is not a drug you would give to a person who's on methadone or some other opioid.
The only other contraindication is decompensated cirrhosis, since naltrexone carries a rare risk of hepatotoxicity. To be clear, patients with less severe liver disease can absolutely take this medication. Child-Pugh class indicates the severity of chronic liver disease were class A means well compensated, class B means significant compromise, and class C represents decompensated disease. You can prescribe naltrexone to patients with Child-Pugh class A or B cirrhosis as long as you monitor liver function tests every month or two at first. In terms of timing, there are increasing data to support the idea that giving a shot of intramuscular naltrexone after an alcohol detox at the time of hospital discharge decreases returned to heavy drinking and hospital readmissions.
Our second FDA approved option is acamprosate. Its mechanism of action is complex, but ultimately involves stabilizing the disrupted GABA and glutamate neurotransmitter systems. Unlike the remarkably simple once daily dosing of naltrexone, acamprosate prescribed as 333 milligram tablets taken as two pills, three times a day. It's probably not the best choice for patients who have challenges adhering to medication regimens. Nonetheless, it has been studied in dozens of randomized controlled trials with many 1000s of patients and has been shown to be just as effective as naltrexone, particularly for those hoping to maintain abstinence. The most common side effect is diarrhea occurring in about one in eight people. An advantage of acamprosate is that it is renally rather than he hepatically cleared, so it can be used regardless of the extent of a patient's liver disease. Patients with a glomerular filtration rate or GFR between 30 and 50 need half the dose, and patients with a GFR less than 30 should get a different medication entirely.
And our last FDA approved option is disulfiram. Disulfiram is unique among medications in that it works as a deterrent. Let's look at the metabolism of alcohol first to understand disulfiram's mechanism of action. Alcohol is normally metabolized in the liver by the enzyme alcohol dehydrogenase, which breaks it down to its primary toxic metabolite acetaldehyde. Acetaldehyde is then quickly broken down by acetaldehyde dehydrogenase to acetic acid, which is readily excreted in the urine. Disulfiram blocks this second step where acetaldehyde is converted to acetic acid. This leads to the accumulation of toxic acetaldehyde which is very unpleasant to the patient. In essence, if a patient taking this medication drinks any alcohol, they're going to have a very bad day. Flushing, headache, nausea, vomiting, palpitations, it's miserable.
For patients who successfully avoid alcohol however, disulfiram is quite well tolerated with rare side effects. These can include headache, hepatotoxicity, and neuropathy. Disulfiram is taken as a 250 milligram pill, once daily, though, we often start with a 500 milligram loading dose for the first week. Since medication adherence can be challenging for medication that causes terrible symptoms, even the most motivated patient may be hesitant to take their morning dose from time to time. So this treatment is most effective when a patient has strong social support at home, helping to encourage them to take their dose. In such circumstances disulfiram is remarkably effective at maintaining abstinence, and can really be quite liberating for patients previously suffering from daily cravings. Having reviewed those three options, let's talk about when to prescribe them.
Maintenance pharmacotherapy should be offered to any patient with AUD, who is either actively drinking or is experiencing cravings to drink. That will certainly include patients admitted to the hospital for alcohol withdrawal, where it should be started before the patient gets discharged. Better yet, start them before your patient gets admitted. It can and should be offered by emergency room providers, hospitalists, primary care providers and psychiatrist. They're easy to prescribe and require no more training than having watched this video. We typically recommend at least three to six months of treatment with these meds, though there's no harm in continuing them indefinitely for patients who are still struggling or those with ongoing risk of relapse. Insurance policies cover each of these medications because they are effective, and they ultimately save the healthcare system money when patients take them. So, please prescribe them.