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Friday, 15.12.2017

Paul Devenyi MD, FRCP is former head of medical services Addiction Research Foundation, Toronto Ontario, Canada.

PHARMACOTHERAPY OF ADDICTIONS - NOT A SUCCESS STORY

By Paul Devenyi 

As an internist I somehow strayed to this website and got myself embroiled in some controversies about my view that addictions are not treatable diseases, perhaps not diseases at all, but self-induced irresponsible behaviors of choice. This point of view is not popular, of course, and not politically correct. Unless psychiatrists and behavioral scientists come up with some useful behavioral strategies, the future does not look promising. I came to this conclusion after 50 years of (wasted?) career in addiction medicine where I was involved more in the management of medical problems and complications than in addiction per se.  Since programs ranging from 12 steps to individual and group counseling did not produce overwhelming success, there was an increasing demand from public and professional circles, that we come up  with some viable pharmacotherapies, whereby the addicts go home with a prescription, take  it and presto, he is no longer an addict. I thought it would be appropriate to this website to briefly review the available pharmacotherapies, which so far have not been a success story.

The oldest drug therapy for alcoholism has been Disulfiram (Antabuse) with more than 60 years history and still going. The drug arrests alcohol metabolism at the intermediate acetaldehyde level and the accumulating acetaldehyde causes a variably unpleasant reaction. The idea is that the alcoholic voluntarily takes the drug and if he drinks on it, gets punished therefore he would be too scared to drink. Attempts were even made with involuntary administration such as by a concerned spouse or an employee health nurse; these attempts usually fail, because alcoholics are clever to cheat and wiggle out of the forced administration. Voluntary use of the drug, which is the standard today, is unsuccessful because the minority of alcoholics who accept it at all, don't take it long enough to be useful. I just mention in parenthesis that depot injection of disulfiram was abandoned, because the drug does not absorb reliably from depot sites.

For opioid addiction a feasible treatment appeared to be naltrexone, an opioid antagonist which - by blocking the receptors - would render the opioid ineffective, thus  wasteful. It was assumed that the narcotic addict would voluntarily protect himself from the pleasures of his drug, thus won't use it. Like with disulfiram, the trouble is that most addict won't take it and certainly not long enough to extinguish the dependency. A few years ago reports appeared that naltrexone, in a non-specific way somehow decreases alcohol craving, thus people would find it easier to abstain or would drink less. To my knowledge this did not catch on and I did not find a single alcoholic in my practice, to whom it did anything. Similar anti-craving effect has been claimed for acamprosate (Campral), long popular in Europe and relatively new in North America, which supposedly controls the alcohol craving of the already detoxfied alcoholic, thus he won't drink again.

In the 1980s Doug Teller and I ran a study on  bromocriptine,  for cocaine addicts, a dopamine antagonist which supposedly diminished cocaine craving, by decreasing the pleasure-causing effect of dopamine (Cocaine increases dopamine in the brain). We could not distinguish the effect from placebo.

Methadone, a long acting opioid is an old and more or less accepted drug substitute treatment for heroin and sometimes other opioid addiction. In my view, true and long lasting successes are not unheard of, but rare. Buprenorphine, a partial opioid agonist with a long half-life, has been used in the last few years for opioid dependence and withdrawal, preferred by some over methadone. I don’t know of any overwhelming success; personally I did not use it.    

Several drugs are used in addiction medicine for detoxification or drug withdrawal. “Cold turkey” withdrawal is inhumane and at times dangerous.

Depressant drugs are withdrawn gradually to avoid unpleasant and sometimes dangerous withdrawal symptoms. As such, it is a successful treatment. As to maintain a drug free lifestyle, withdrawal tapering seldom has a lasting impact. In principle you taper the same drug what the patent was using or a long acting equivalent, such as methadone for opioids and diazepam for benzodiazepines. Alcohol is an exception; you don’t use alcohol for its withdrawal, the commonly used drugs are benzodiazepines, thiamine to treat or prevent Wernicke encephalopathy and peripheral neuropathy, haloperidol for delirium tremens.

Non-depressant drugs, such as cocaine, cannabis, etc. do not require tapering.

A newer and intriguing approach to addictions - still in experimental phase - is immunization. At Cornell, they experimented with cocaine vaccine: cocaine, a small molecule that is complexed with a large protein (common cold virus), producing a cocaine antibody response when exposed to the drug and prevents cocaine to reach the brain and produce euphoria. The Chileans are working on an alcohol vaccine. This is an entirely new avenue to treat addictions and some animal experiments have been promising. One still has to doubt that this will be the panacea. It is not just the question that will it work, but whom, at what age, under what circumstances to vaccinate? The medical ethicists would have a field day.

Finally, a word about cigarette addiction. I am not a believer that the various pharmaceutical agents are that effective (Nicotine substitution, Zyban, Chamtix). A lot of people quit spontaneously and the major factor is social pressure:  education, propaganda, legal restrictions   -   the very factors that are mentioned in my first essay in controversies that can have more of an impact on addictions than drugs or individual treatment techniques.

Paul Devenyi
December 5, 2013