Letters

From the April 1997 issue

(Page 2 of 5)

The article fails to accurately describe the toxicity of narcotics. The author states that "compared to other pharmaceuticals, opioids are remarkably safe: The most serious side effect of long-term use is usually constipation, whereas over-the counter analgesics can cause stomach, kidney, and liver damage." In fact, opioids are lethal. As the book The Pharmacological Basis of Therapeutics says: "By the time he is seen by the physician, the patient who has taken an overdose of an opioid is usually asleep or stuporous. If a large overdose is taken, he cannot be aroused and may be in a profound coma. The respiratory rate is quite low (sometimes only 2 to 4 per minute), and cyanosis may be present. As the respiratory exchange becomes poorer, blood pressure�falls progressively.�If hypoxia persists untreated, however, there may be capillary damage, and measures to combat shock may then be required.�Urine formation is depressed. Body temperature falls, and the skin becomes cold and clammy. The skeletal muscles are flaccid, the jaw relaxed, and the tongue may fall back and block the airway. Frank convulsions may occasionally be noted.�When death occurs, it is nearly always due to respiratory failure�or as a result of complications such as pneumonia or shock that develop during the period of coma."

As a wide variety of drugs are classified as opioids, crucial reactions may vary over the class. Nonetheless, the toxicities of the commonly used drugs such as morphine, meperidine, and codeine include respiratory depression, nausea, vomiting, dizziness, mental clouding, dysphoria, urinary retention, and hypotension. Frequently prescribed opioids like propoxyphene (used in Darvon) can have additional effects such as convulsions and toxic psychosis.

Finally, there is the addictive potential of these drugs. The consensus is that with proper use, rates are not high but they are significant. Unfortunately, adequate studies are hard to find. However, the rates are sufficiently high that a significant number of patients will experience addiction. Thus, the drugs need to be used with strict supervision in the appropriate setting to minimize addiction with its debilitating consequences.

The author fails to understand how the conditions of use can affect the addictive potential of the drug. His initial anecdotes concern treatment of chronic pain in outpatients. He also reflects on the use of these drugs by patients with terminal cancer and quotes health care professional in regard to these patients without drawing a clear distinction. He further muddies the waters by mixing the acute treatment of pain in the hospital with that of chronic pain patients. As an example, he cites 11,882 hospitalized patients treated, with only 0.034 percent becoming addicted. Later in that paragraph he cites 38 chronic pain patients of which two became addicted. The difference between the two groups is compelling: The hospitalized patients had an addiction rate of 0.034 percent, whereas the chronic pain patients had a rate of 6 percent. Thus, the two groups differ almost 200-fold in potential for addiction. The ramifications of an addictive rate of 6 percent are catastrophic and unacceptable. (To some extent I am playing the author's game here by over-interpreting data on a population that is too small for statistical significance and is poorly characterized clinically and demographically.)

A rational reader without prior medical training could easily draw unreasonable conclusions from this article. The information in it can lead the untrained reader to conclude that narcotic analgesics are safe -- even safer than aspirin or acetaminophen (Tylenol), the "over-the- counter analgesics [which] can cause stomach, kidney, and liver damage." The reader might reasonably act on this information and substitute these "safe" (opioid) medications for aspirin or acetaminophen for headache relief. The consequence to the unsuspecting reader could easily be addiction, if not the acute toxicities noted above. I can only hope that one of your readers does not take the medical information in your article seriously and suffer consequences because of it. If nothing else this untoward potential should alert you to the care necessary when you indulge in writing medical articles. That care was not taken in this case. Thus, the article does a disservice to its readers because of an unintended but potentially lethal medical consequence.

The regulations and intimidation cited in the article are a good example of what happens when medical decisions are left to those not trained in medicine. Let us not conclude that the consequences of these regulations and our abhorrence of them indicate that the drugs they regulate are benign. The regulations are not benign and neither are the drugs. The author should have stuck to the issue of regulatory intimidation and not strayed into interpretation of medical data.

William Vine, M.D., Ph.D.
San Diego, CA

Jacob Sullum replies: I thank Mr. O'Hara and Mr. Weiner for their letters. The responses to my article, including several private communications from physicians, have been uniformly positive, with the exception of Dr. Vine's lengthy complaint. I am a bit puzzled by his condescending attitude, especially since he seems to agree with my thesis. I plead guilty to the crime of using anecdotes "to create empathy"; lock me up, along with every other journalist. As for the rest of the charges�

Dr. Vine accuses me of using "intellectually bankrupt methods," yet he fails to cite a single inaccuracy, logical fallacy, or piece of countervailing research. By using scare quotes, he insinuates that my sources are not really experts, but he does not explain the basis for that judgment. He says I used their comments "out of context," but he does not offer any examples.

When he gets down to specifics, Dr. Vine objects to my statement that, "compared to other pharmaceuticals, opioids are remarkably safe: The most serious side effect of long-term use is usually constipation, whereas over-the-counter analgesics can cause stomach, kidney, and liver damage." I was referring to long-term use of high doses for the treatment of chronic pain. In this context, opioids generally are preferable to aspirin, acetaminophen, and ibuprofen. Some patients treated with narcotics experience side effects other than constipation, including those cited by Dr. Vine, but these are either unusual or less serious. More important, opioids do not cause organ damage, even in people who take large doses every day for years.

Dr. Vine notes that "opioids are lethal," but so is any drug (including aspirin) in a large enough dose. In discussing the long-term safety of narcotics for the treatment of chronic pain, I assumed, not unreasonably, that doctors would not prescribe lethal doses and that patients would follow their instructions. Since I described the case of a patient who failed to do so and died as a result (and also referred to "doses of narcotics that would kill the average person"), the risk of overdose should have been plain even to readers who had never heard that opioids can be fatal.

My article was about the impact of drug policy on pain treatment; it was not intended as a guide to the advantages and drawbacks of narcotics. The notion that my passing comment about long-term toxicity might lead someone to take (illicit?) opioids instead of Tylenol the next time he gets a headache is a bit of a stretch, I think. And for the reasons outlined below, it is misleading to say that the result of such a decision "could easily be addiction." Even so, Dr. Vine's concern that I did not pay enough attention to the hazards of narcotics is reasonable. In an earlier draft of the article, I noted that some patients, including David Covillion, experience severe (though not life-threatening) side effects from opioids. That passage was eliminated during the editing process. Had space allowed, I would also have discussed the risk of respiratory depression, which can complicate the treatment of patients who are near death (though it is not an issue for chronic pain patients like Covillion).

Dr. Vine claims that I do not describe a single painkiller addict. I take it he does not count my references to addiction among Civil War veterans and patent medicine consumers, or my discussion of Mary Tyrone in A Long Day's Journey into Night (a character modeled after Eugene O'Neill's mother). Nor did he notice my description of drug abuse by one of William Hurwitz's patients. I suppose I could have thrown in Johnny Cash, and maybe Michael Jackson too, but somehow I doubt that would have satisfied Dr. Vine.

I never denied that some patients treated with narcotics continue taking them for non- medical reasons. I simply reiterated what appears to be the consensus among pain experts (in my reading and interviews, I did not come across any who disagreed): that such outcomes are rare. This conclusion, which Dr. Vine seems to concede, is supported by substantial research during the past few decades, including, but not limited to, the reports I cited.

Dr. Vine is correct that different studies in different contexts have found different rates of "addiction" or "drug abuse" that could be traced to pain treatment. It stands to reason that a patient who takes a narcotic for many years is more likely to get psychologically hooked on it than someone who gets a dose or two after surgery. But even in the study of chronic pain patients to which he refers, both individuals who developed problems had histories of drug abuse (as did Johnny Cash). This is an important fact, because it illustrates that addiction is not simply a drug effect; circumstances and personality play crucial roles in determining an individual's relationship with a given substance. That's why talking about a drug's "addictiveness" can be misleading. As former National Institute on Drug Abuse Director Charles Schuster, no wild-eyed drug legalizer, put it, "We have endowed these drugs with a mysterious power to enslave that is overrated."