A Matter of Interpretation

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Columns - From the Addiction Physician

Written by Stuart Gitlow, MD, MPH, MBA

Friday, 27 May 2011 11:33

A group of six authors recently wrote the article, “Opioid Antagonists for Alcohol Dependence,” and saw it published as part of Wiley’s Cochrane Library. The article title appears to indicate that opioid antagonists might be useful in the treatment of alcohol dependence, and indeed the conclusion of the authors reads: Naltrexone appears to be an effective and safe strategy in alcoholism treatment.

The authors reviewed 50 studies with nearly 7,800 participants. The review summary indicates that more patients who took naltrexone were able to reduce the amount and frequency of drinking than those who took placebo. They continue by noting that one of nine patients taking naltrexone were helped by the drug. However, when one leaves the summary to read the actual results of the review, a different story is portrayed.

Naltrexone reduced the risk of heavy drinking to 83 percent of the risk of the placebo group. That risk ratio is not a particularly strong endorsement of naltrexone, but more importantly, the outcome measure is completely unimportant. No research has ever demonstrated that a reduction in heavy drinking frequency by patients with alcohol dependence results in any improvement in morbidity or mortality. There are studies demonstrating that alcohol intake, if reduced in non-alcohol dependent individuals, has a benefit, but it is a long leap to presume that such benefit would also be present for alcohol dependent patients, who have very different morbidity/ mortality curves when compared with the general public.

Naltrexone was noted to reduce drinking days by 4 percent. If an alcohol dependent patient reduces the number of drinking days within a 100-day timeframe from a 50- to 48-day timeframe, would you consider that to be an improvement?

The big finding in the review comes when the authors note that the effects of naltrexone on return to drinking missed statistical significance. That is, the impact of naltrexone failed to show any difference from placebo in terms of leading the alcohol dependent patient to maintain sobriety. Since sobriety, abstinence, and recovery are our goals for the treatment of addictive disease, naltrexone is demonstrated here not to work.

Importantly, this is not a harm reduction versus abstinence discussion. There is no evidence that naltrexone results in harm reduction either. For that to be present, one would first have to demonstrate that alcohol dependent patients have a reduction in morbidity or mortality secondary to either a 4 percent drop in drinking days or an almost negligible, though statistically significant, alteration in frequency of heavy drinking days. Note, for example, that an individual who decreases drinking days and days of drinking heavily might still actually be drinking a larger volume of alcohol over a period of time than he or she was imbibing prior to the change.

The authors’ conclusion, that naltrexone is an effective strategy in alcoholism treatment, is neither supported by the data nor by the authors’ own study results,but there is one more problem. The authors speak of alcohol dependence in their article title, as do the authors of the many studies included in the overall review. They then speak of alcoholism in their conclusion. Alcoholism is not alcohol dependence.Alcohol dependence is a specific diagnostic entity described and defined in the APA’s diagnostic manual,

DSM-IV. Alcoholism is a specific disease entity described in consensus documents published at various times over the past several decades. The biggest difference between the two is that alcoholism addresses use of drugs cross-tolerant with alcohol. Alcohol dependence does not, with the APA utilizing the term sedative dependence for all other drugs that work in the brain as alcohol does. The result of these differences is that studies looking at alcohol dependence specifically do not generally look closely, if at all, at the use of benzodiazepines, barbiturates, and other similar drugs. This introduces an enormous variable since a patient can switch from alcohol to diazepam and look as if he is improving on an alcohol-only consideration basis. In fact, there has been no improvement at all or we could stop all alcoholism in its tracks by simply substituting pills for drink. Note that by definition, if we substituted pill for drink, we really would be stopping all alcohol dependence.

The opioid antagonists article was picked up by various media and circulated widely among newsgroups with interest in the addiction field. The summary which I saw most frequently focused on the authors’ conclusions without any associated commentary. The actual results of the study were not incorporated into the distributed information. There are significant risks likely to be associated with the use of a useless drug:

1. There are economic costs associated with pharmacotherapy.

2. There are potential side effects associated with pharmacotherapy.

3. There are risks of delaying beneficial treatment.

4. There are risks of leading the patient to believe that a pill or injection can save them from an illness where that patient mistakenly has believed that problems can be cured by taking something.

Entirely missed in the review is all the evidence indicating that we have quite effective approaches available in the treatment of those with alcohol dependence. The approaches are so effective that physicians and other healthcare providers are able to return to their work, as are airline pilots and military personnel, after a short period of initial treatment and with ongoing treatment. Most longterm studies demonstrate that over 75 percent of these treatment participants are able to remain abstinent and unlimited in their occupational capacity. In the study reflected above, the authors noted a comparison between naltrexone and placebo, but failed to even mention that standard treatment without utilizing any drug is better yet.

I urge readers to look very closely at the actual evidence behind statements regarding pharmacotherapeutic treatments of alcohol dependence.

Stuart Gitlow, MD, MPH, MBA, a psychiatrist, is a member of the American Medical Association’s Council on Science & Public Health, and an officer of the American Society of Addiction Medicine. This column represents his personal opinion and does not imply any position or policy taken by either the AMA or ASAM.

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