For your patients that you've screened and diagnosed with alcohol use disorder, you can manage symptoms with medications just like you would for many other chronic illnesses. We hope by this point, you don't believe the perpetuated myth that prescribing medications is trading one addiction for another. The medications you will learn about in this lesson help people manage intense cravings, help them reduce the amount people drink, or promote periods of no drinking or abstinence. Let's pause for a quick question. Which of the following medications have you heard about before? Naltrexone, Acamprosate, Disulfiram, Topiramate or Gabapentin? If you've heard of all of them, great. You probably have experienced working with this patient population. But if you haven't, that's totally fine too and we're going to go over them right now. The four FDA approved medications for alcohol use disorder include oral Naltrexone, injectable Naltrexone, Acamprosate, and Disulfiram. There are two additional medications, Topiramate and Gabapentin, that are worth mentioning as well. Please note that all of these medications can be prescribed in a general medical office. There no DEA restrictions as there are with medications to treat opioid use disorder. To date, Naltrexone and Acamprosate have the best available evidence and are considered first line treatments. So let's start with Naltrexone. Naltrexone has been associated with a reduced likelihood of return to drinking and with fewer drinking days overall. It's also thought to decrease that subjective experience of craving which are those strong often intrusive urges to drink. Oral Naltrexone was actually initially FDA approved to treat opioid use disorder but has also been discovered in clinical trials to decrease alcohol consumption through its action at the opioid receptors. Naltrexone is an opioid antagonist or a blocker, meaning it binds to and then blocks the activation of opioid receptors, effectively turning them off. It's important to tell patients about the opioid blocking effect. If a patient is currently taking opioids, Naltrexone may send them into precipitated opioid withdrawal which is very uncomfortable. If opioids become necessary in the future for surgery or an unexpected trauma, then Naltrexone may affect the patient's pain relief. Naltrexone is available in both a daily oral and monthly intramuscular injection. The recommended dose of oral Naltrexone is 50 milligrams daily. However, some people may require up to a 100 milligrams a day. For the long acting Naltrexone, the dose is 380 milligrams IM every four weeks. Naltrexone is generally well tolerated with some potential side effects that we're going to discuss here. The most common being nausea, dizziness, vomiting, diarrhea, and abdominal pain. Additionally, though the risk is very low, Naltrexone may affect liver function and this will more commonly occur in patients with other liver problems such as Hepatitis C, cirrhosis due to alcohol or other causes. Ongoing alcohol use is typically far more damaging to the liver than is Naltrexone though, and this becomes part of the discussion that you should have with your patients. When starting Naltrexone, it's important to check liver function tests prior to treatment and to monitor clinically throughout. For patients with significant liver problems, there's another evidence-based medication for alcohol use disorder called Acamprosate. Acamprosate is largely excreted by the kidneys and it's not metabolized through the liver. The exact mechanism of action isn't clear, but it may act through its effect at the glutamate receptors. The main treatment effect found in clinical trials was that it helped maintain abstinence in people who had achieved no drinking status, so they'd achieved abstinence. Acamprosate is effective in the treatment of alcohol use disorder at total doses around two thousand milligrams or two grams which is usually divided into 666 milligram tablets taken three times a day. So that's something to talk to patients about. Taking medications three times a day sometimes can be very helpful and reinforced motivation for patients, but other times, three times a day might be a burden. It's recommended to start as soon as abstinence is obtained and to continue it regardless of drinking status. So even if a person returns to drinking, just continue prescribing. The most common side effect for Acamprosate is diarrhea and since this medication is largely excreted by kidneys, you would want to check serum creatinine at baseline and then the dosing may need to be reduced in patients with kidney dysfunction. Another medication option is Disulfiram and it should be considered for patients who have a goal of abstinence, who've not responded to Acamprosate or Naltrexone, or for those who prefer it. Disulfiram is the oldest medication for treating alcohol use disorder and it's also known as Antabuse. It's been around for decades and it works by making people feel sick when they drink. Disulfiram inhibits the enzyme aldehyde dehydrogenase which breaks down the ethanol byproduct, Acetaldehyde. So when ethanol is consumed by somebody who's on Disulfiram, Acetaldehyde builds up or accumulates and it produces unpleasant sensations, a rapid heartbeat, flashing, headache, nausea, lowered blood pressure, and vomiting. Patients on Disulfiram develop anticipatory fear of using alcohol and therefore, it can help reinforce motivation toward abstinence. Before starting, you must make sure your patient understands the physiologic consequences of drinking alcohol while taking Disulfiram. They should not drink anything at least 12 hours before starting the medication. Reactions to alcohol can occur up to 14 days after stopping Disulfiram. Patients need to be warned that ethanol may be found in lots of things such as some cold and flu treatments, mouthwashes, hand sanitizers, food, and even other medications. Additionally, Disulfiram has been associated with mild increases in liver enzymes in up to one-quarter of patients. Although extremely rare, acute hepatotoxicity can occur sometimes, with life-threatening consequences. The rate is roughly one per 10 to 30,000 cases. Like Naltrexone, it's important to check liver function tests throughout treatment. So I've just told you the major risks of Disulfiram but I really want one of the take-home messages of this lesson to be that Disulfiram is an underutilized medication. Research has shown that Disulfiram is very effective on par or even outperforming other medications to treat alcohol use disorder particularly, when medication adherence is supervised by either a treatment team or by a significant other. Finally, we're going to discuss two medications that have some strength of evidence but that are not FDA approved. If your patient has given Naltrexone a try with little success, then consider Topiramate. Just because one medication isn't a good fit, it doesn't mean to give up. Topiramate has been shown to reduce cravings and it may help reduce post-withdrawal anxiety and low mood. Studies have shown that the effect size for abstinence is moderate and it also appears to reduce the number of heavy drinking days and cravings. The suggested schedule for Topiramate is 25 milligrams a day for a week and then increasing by 25 milligrams each week with a target dose of 200 milligrams. So it might take four to six weeks to reach an optimal dose. One important thing to note, Topiramate needs to be titrated slowly given its risk of cognitive problems such as word finding difficulty and other issues with memory or concentration. Other side effects may include weight loss so potentially consider this in patients with obesity. It also causes sedation and gastrointestinal side effects. Despite occurrences being rare, you will want to keep an eye out for metabolic acidosis, kidney stones and glaucoma. Assess baseline cognitive status and kidney function in these patients. Last but not least, let's review Gabapentin. Gabapentin is a medication often used for neuropathic pain but it's also been found useful for patients with alcohol use disorder to increase rates of abstinence, and to reduce heavy drinking, and help with cravings, mood, and insomnia. Gabapentin can also be used to adjunctively for alcohol withdrawal syndrome so you could initiate a patient when they're experiencing withdrawal and then titrate up for higher doses for craving. Effective doses range between 900 and 1800 milligrams daily. In studies, reported side effects were minimal with the most common side effect being fatigue, insomnia, and headache but the rates didn't differ from placebo. Gabapentin is excreted unchanged in the kidneys and dosing should be adjusted in patients with significant kidney disease. Be mindful also of patients who have other substance use disorders as there's increasing evidence that Gabapentin may be misused. All right. So we've discussed all of these medications but how might we decide on one medication versus the other? In general, it's recommended to start with one of the first line FDA approved medications for alcohol use disorder. So that's either Naltrexone or Acamprosate. But turning to Disulfiram, Topiramate, or Gabapentin should not be delayed if there is a good rationale such as a trial of Naltrexone or Acamprosate simply wasn't effective or a patient prefers one over the other. How you might decide on one medication versus another really does depend on the patient's treatment goals and other health-related factors. If a patient, for example, has a goal of complete abstinence, then we'll typically talk about Acamprosate or Disulfiram. On the other hand, if a patient doesn't have a goal of abstinence but wishes to take a medication only on days when heavy drinking are anticipated, then oral Naltrexone would be a good choice. Aside from the patient's treatment goals, sometimes we consider comorbid illnesses when choosing a medication. So for example, if a patient is currently prescribed long-term opioids for chronic pain, then Naltrexone is absolutely contraindicated and you're going to have to start with another medication. If someone has significant liver dysfunction, you may first trial Acamprosate which is not metabolized by the liver but excreted by the kidneys. Alternatively, if a patient has chronic neuropathic pain, then consider the Gabapentin because it can have a dual action. In someone with migraine headaches or obesity, you might think of Topiramate. Let's pause for some questions. In summary, there are for FDA approved medications and two promising alternatives. Each works slightly differently and can be recommended to patients depending on their medical history and their treatment goals. Try not to get discouraged if a medication does not appear to be working as there likely will be some trial and error to this. There's a chart you can download in the resource section containing each medication we covered and it's corresponding mechanism of actions, dose, side effects, and contraindications. These are just the basics to get you started and we recommend consulting the prescriber medication guide for complete details before prescribing these medications.
