Antabuse Antabuse (disulfiram) is an older drug that has been around since the 1950s. everybody calls this medication Antabuse, (the brand name); disulfiram is the chemical or generic name, and it is used in the treatment of alcohol addiction. Anyone who takes this medication and drinks alcohol while he or she is on it will become violently sick and can actually die. Antabuse interferes with the body’s metabolism (breakdown) of alcohol. When you drink, your body metabolizes the alcohol so you can process and ultimately excrete it. Alcohol is broken down into different chemicals, primarily in the liver, and these chemicals are then eliminated through urination and sweating. One of the steps of this breakdown is the production of an enzyme called aldehyde dehydrogenase. Antabuse inhibits this enzyme, interfering with the process of metabolism. So instead of continuing to break down the alcohol so it can be excreted, a toxic by-product called acetaldehyde builds up in the blood. High levels of acetaldehyde act directly on the heart and blood vessels, causing flushing, a racing heartbeat, and a drop in blood pressure that causes dizziness. Other extremely unpleasant symptoms include headache, shortness of breath, palpitations, nausea, and vomiting. This combination of reactions to alcohol is often called the “disulfiram reaction,” and is usually adverse enough to deter people from continuing to drink. Patients are well informed that when they take Antabuse, drinking will make them sick, and this deterrent often helps people avoid alcohol. Years ago, we would tell the patient to try drinking a small sip of alcohol while on the medication just to get a sample of what the reaction would be like. We don’t recommend that technique anymore. Now we just tell people what to expect if they take the medication and give them a brochure about the side effects. Some people actually wear a bracelet that says they’re on Antabuse in case something happens to them so that medical personnel will be prepared. Antabuse is remarkably free of side effects, although some people do get a skin rash or an upset stomach, but most people don’t. And if they stop their medication the side effect goes away quickly. Once you begin taking it, the effects of Antabuse last in the system about twenty-four to forty-eight hours and sometimes as long as seventy-two hours. Be aware that some people are very sensitive to Antabuse, and after they apply aftershave or cologne they start getting a rash. Even mouthwash can cause a reaction because many of these products also contain alcohol. Other people are not that sensitive and we have to double the dose. Antabuse comes as a 250 mg pill and also a 500 mg pill so we can start with the lower-dose pill and raise the dose to 500 mg per day if the weaker dose doesn’t work. It’s like an insurance policy. Some people take it around the holidays or if they’re going to go to a wedding and they don’t want to drink. They start taking this medication a few days before the event, and they know if they drink they’re going to get very, very sick. Some addicts actually plan their relapses. They know that they’re going to relapse at the end of the month so they stop taking it the prior week. Some legal enforcement programs actually require the patient to take Antabuse. And if someone is required to take it and he or she provides a urine sample that doesn’t come up positive for Antabuse, he or she may have consequences for noncompliance. Antabuse can also be used strategically. Addiction counselors working in outpatient treatment settings usually impress upon their clients that the first week of abstinence is not a very good time to go to a wedding or to a New Year’s party, and that they would be well advised to avoid places where a lot of alcohol is served. But some circumstances are extraordinary: “My daughter is getting married next week and I have to be there. I can’t not go just because alcohol will be available.” A counselor can help the client connect with an addiction medicine physician to be prescribed Antabuse and suggest that he or she start taking it a few days before the wedding and keep taking it. “You need to take it every day while you’re away for the wedding to keep you from drinking because if you have the urge to drink, you know that if you act on it, you’ll get violently ill and maybe wind up the hospital instead of enjoying your daughter’s wedding.” I had one patient who believed that visiting his mother was a relapse trigger for him so a few days before he went to San Francisco to visit her, he started taking Antabuse, and he continued to take it as long as he was there. when he got home and that stressor was gone, he stopped taking it. As useful as Antabuse can be, it’s not perfect. It is possible to die from this medication and some people develop a tolerance to it. I’ve had people say it doesn’t work very well, and some are able to drink around it. So some people are very sensitive to it and some people are less sensitive to it. Patients on Antabuse should have their liver function monitored through blood tests because occasionally people suffer adverse liver effects while on it. It’s somewhat paradoxical and frustrating because a lot of alcoholics already have liver problems, so their liver functioning is already abnormal. But if the choice is between such persons continuing to use alcohol and taking Antabuse, as a physician, I’d much rather they take the Antabuse. Naltrexone Naltrexone (brand name Revia) is another important medication in addiction treatment. Naltrexone is an interesting medication. It was originally developed as an opiate antagonist to be given to opiate addicts to block the euphoric effects of heroin. The neurochemistry is that when the effects of opiates are blocked, you don’t get the high, you don’t get the rush, and you don’t get the “feel good” experience. The thinking went that if those who used heroin didn’t get high, they would have little reason to use. However, in my practice of addiction medicine I have encountered addicts who stubbornly increased their dosage of heroin in an attempt to override the blocking effects of naltrexone. Unexpectedly, when naltrexone was given to heroin addicts who also had drinking “problems,” doctors began to notice that many of these patients lost their desire to drink. After observing this side effect, the pharmaceutical company that developed naltrexone realized that it could be used in alcoholism treatment as well. When people drink (or use any mind-or mood-altering substance) there’s a release of neurotransmitters in the brain, and among those neurotransmitters are the endorphins—the body’s naturally occurring opiates. This release of endorphins is part of the body’s automatic response to pain. If you run or do something similar in the way of exercise, your brain releases endorphins, which provide an experience of general well-being and greater calm. If you drink and you’re not getting a buzz and you’re not experiencing any sense of well-being from it, the theory is that you’ll stop drinking. Beyond not getting the benefits of the buzz from alcohol, many of those on naltrexone report a significant decrease in their cravings to drink.Naltrexone was approved for the treatment of alcohol dependence (addiction) in 1994. Some people have used this medication in an effort to drink “less,” and it has been used that way in other countries, though generally, I think this use of naltrexone is inadvisable. In the US, we prescribe it to block cravings and to block the reward that people will get from drinking in order to encourage abstinence. Naltrexone is an effective medication to treat alcohol addiction, especially if it is used in conjunction with traditional treatment and support groups. Multiple research studies have shown it to be effective in reducing relapse rates after abstinence (11). There is now an injectable form of naltrexone, known by the brand name Vivitrol, that lasts about thirty days per injection. It’s a long-acting, oil-based drug, and the patient comes in once a month to get his or her shot. Vivitrol is increasingly being used for opiate addicts, too. If the addict uses an opiate, he or she won’t feel the acute effects because the antagonist blocks them. The use of naltrexone has come full circle insofar as it was originally developed for opiate addiction and then used to help treat addiction to alcohol, whereas the long-lasting injectable form (Vivitrol) was initially used for alcoholism but is now utilized in the treatment of opiate/opioid addiction. A sister drug to naltrexone is Naloxone. Naloxone is an opiate inverse antagonist used to counter the effects of opiate/opioid overdose, for example, heroin overdose. Naloxone is specifically used to counteract life-threatening depression of the central nervous system and respiratory system. when people overdose on heroin or other opiates/opioids, often they are given Naloxone by medical personnel to reverse the effects, frequently saving their lives in the process. Campral Acamprosate (brand name Campral) is a relatively new medication used to treat alcohol addiction. Acamprosate’s mechanism of action in the maintenance of alcohol abstinence is not thoroughly understood, but it is believed to work by restoring the balance of neurotransmitters in patients who have used large amounts of alcohol. Chronic alcohol use disrupts the natural balance, or homeostasis, in our nervous system. Alcohol affects several neurotransmitter systems, but chronic use has a rather significant effect in altering the normal balance between neuronal excitation and inhibition. There is an imbalance between the GABA system, the chief inhibitory neurotransmitter, and the glutamate system, the chief excitatory neurotransmitter. We believe that Campral tends to correct that balance so that the neurons aren’t firing as much—they are dampened and calmed down. Research suggests that Campral works on the glutamate and GABA neurotransmitter systems and restores a more natural balance between them. One of the nice things about Campral is that it doesn’t get processed through the liver. Instead it goes through the kidneys, where it’s metabolized, so this is a medication that can be given to those with liver disease. who has liver disease? Addicts who are long-term alcohol-abusers or have hepatitis C. I have often used a combination of Campral and Antabuse, which I call the “carrot and the stick” (based on the idea that when you want a horse to move, you put a carrot in front of him, and if he doesn’t move, you whack him with a stick). This combination pairs an incentive with an adverse consequence. In this case, the carrot is the acamprosate, intended to help reduce the patient’s desire to drink, and Antabuse functions as the stick that whacks him or her in the event that he or she does use alcohol. At this point, hopefully the patient is also working with a therapist and going to mutual-aid/support group meetings. 10 Mala Szalavitz, “Hazelden Introduces Antiaddiction Medications into Recovery for First Time,” Time, November 2012. http://healthland.time.com/2012/11/05/hazelden-introduces-antiaddiction-medications-in- recovery-for-first-time/ (accessed February 8, 2013). 11 M. Srisurapanont and N. Jarusuraisin, “Opioid antagonists for alcohol dependence,” Cochrane Database of Systematic Reviews 1 (2005). http://www.ncbi.nlm.nih.gov/pubmed/15674887 (accessed January 4, 2013). 12 David A. Feillin, “Buprenorphine: effective Treatment of Opioid Addiction Starts in the Office,” American Family Physician 73, vol. 9 (2006): 1513–14. 99 This blog post is an excerpt from The therapist’s Guide to Addiction Medicine – A Handbook for Addiction Counselors and Therapists – by Barry Solof, MD, FASAM; Published by Central Recovery Press (CRP).