The National Council on Alcoholism and Drug Dependence fights the stigma and the disease of alcoholism and other drug addictions.

Interviews with the Experts

Robert Morse, MD on the Use of Pharmacology in Addiction Treatment

Robert Morse, MD, chair of the NCADD medical/scientific committee, recently retired from the world-famous Mayo Clinic where he was director of addictive disorders.

Q	Could you start by talking briefly about the concept of alcoholism as a brain disease?
A	Dr. Alan Leshner of NIDA (National Institute on Drug Abuse) coined the term "Addiction is a brain disease" a couple of years ago. Through its research in nicotine, cocaine, and opiate addictions (both in animals and in humans), NIDA found that there may be a core biochemical change that takes place in any addiction and has to do with the neurotransmitter dopamine and the nucleus accumbens (a center in the midbrain). In the early 1970s when the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and NIDA were made distinct entities, there arose an unscientific division between alcoholism and other addictions. Actually alcohol fits into the same addiction pathway. Its effects are mediated by several neurotransmitters, in contrast to other drugs that may be mediated by one or two, but it fits this common pathway of dopamine/nucleus accumbens as well. That's the basis of the disease theory as we see it today. Alcoholism has been called a disease for a long time, but we couldn't demonstrate the mechanisms of it like we can now.
Q	Explain the link between alcoholism and anti-depressants.
A	First of all, alcoholism itself can cause depression. One of the most important things to teach physicians is that an alcoholic who seems depressed, either while drinking or within the first couple of weeks after stopping, may be depressed just because he or she is alcoholic. That kind of depression may mimic what we call a major depression. You should wait at least four weeks after abstinence before you even consider using anti-depressant drugs. Then they should be as effective for abstinent alcoholics as for non-alcoholics. People who go back to drinking and are taking antidepressants often do poorly for a lot of reasons. The antidepressant itself is not going to be as effective when you're also taking a drug (alcohol) that can cause depression. Also it's very seldom that an alcoholic who is drinking will take the antidepressant regularly. There's also a concern with drinkers' faulty memories. They may either deliberately or unintentionally take an overdose, which can of course be fatal. You ought to try to get the drinking stopped before you go after the depression.
Q	How do prescription drugs to treat alcoholism work?
A	There are only two drugs approved in this country for alcoholism. One is naltrexone, and the other is Antabuse, or disulfiram. Naltrexone is an opiate antagonist and has been known for 20 years or more as a drug that would interrupt the opiate high. It was then discovered that naltrexone reduced the tendency to drink alcohol in alcohol-preferring rats. In humans and human alcoholics, it seemed to have a distinct positive effect. In a double blind study over three months, almost twice as many on the active drug remained abstinent as those on the placebo. We have good evidence that this is a helpful drug. It's not habit-forming. It has relatively few side effects. It seems to reduce craving in alcoholics. Disulfiram has been around since the early 1940s, when Scandinavian researchers who were looking for a cure for roundworm infection discovered it. They took disulfiram themselves (as some researchers do) and they found that they couldn't drink wine without getting sick. It was a serendipitous finding. Even though it didn't help with worm infections, they'd stumbled onto something that would help with drinking problems. There's a biochemical pathway by which alcohol is broken down in the liver. It goes through a series of steps, and disulfiram blocks one of the steps of metabolism, so a compound called acetaldehyde builds up in your bloodstream. Acetaldehyde is a compound that makes you sick if you drink alcohol. It works with virtually all people. If you're taking disulfiram and drink a little alcohol, you get a predictable reaction. It usually starts with flushing of the face and skin. You feel hot and may get a headache and dizziness. If you drink a lot, you may get very sick and have a drop in blood pressure. There have been a few life-threatening situations. It's very uncommon though, because most people will stop drinking as soon as they get the reaction, which occurs within about five minutes of starting to drink. What we've learned is that disulfiram works well as a deterrent if you can make sure the patient ingests it. Disulfiram's main drawback is that it comes in a tablet form. It's not yet available as a depo-injection that would last a long time. So you give a prescription to an alcoholic who may take it for a month or two and get the urge to drink, then have the choice between drinking or taking Antabuse. You know what happens! With our local patients at Mayo, we'll have them come in to our nursing station on a daily basis and take disulfiram in front of our staff. They know that they're taking it, and their family knows that they're taking it. If the drug is monitored this way, it is a very effective deterrent. Unfortunately most of the studies on its effectiveness were not done in that way. Therefore the literature on disulfiram does not look very helpful. There's an interesting drug available in Europe called Acamprosate. We think it will be approved in this country fairly soon. It's been studied with literally thousands of patients. It seems to act on one of the neurotransmitters, glutamate, which is activated by alcoholic drinking. One of the triggers to drinking in alcoholics is the overly anxious, stimulated feeling that comes in early sobriety, making it hard to slow down, sleep or rest. Acamprosate seems to reduce that kind of stimulation. In several double blind studies in Europe, it's been helpful. It's in the stages of being reviewed by our Food and Drug Administration (FDA), and some programs in our country are using it experimentally right now. So I think that will be the next thing on our horizon. I have hopes that there is going to be a kind of therapeutic breakthrough in the next decade. I hope we'll have more useful, safe drugs, and a treatment system that will accept them better.
Q	Would it be accurate to say that there's rarely a patient who would be helped with only drugs?
A	Yes, and the FDA rightfully approves naltrexone only for use with patients in alcoholism recovery programs. Naltrexone and disulfiram may be very helpful in keeping the patient abstinent. However medications do nothing about the psychosocial factors--a patient's emotional life, getting a patient's family back together, resurrecting a patient's job or getting a patient out of jail, for example. We're always going to need psychotherapy and psychiatric care for those who have mental disorders. Now we're approaching a time when we may be able to alter biology in order to speed up and enhance treatment. If I were a counselor or psychotherapist, I'd look forward to having a patient on a medicine that helped him or her stop drinking, so I could help the patient work with the psychosocial/emotional/cognitive issues of recovery. It's a matter of integrating biological, psychosocial and pharmacological approaches. All are helpful and necessary.

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