THE SCAR HYPOTHESIS
Was anxiety, depression, or any other psychic problem the cause of Lee’s pain? Or was her pain making her miserable?
It is generally estimated that between one-third and one-half of people who suffer from chronic pain also have a major depressive disorder. Conversely, pain is a frequent complaint in the psychiatric clinic: a Stanford University study of major depression found that almost half of those who are depressed also suffer from chronic pain. But the relationship between pain and depression turns out not to be one of those pointless chicken-and-egg questions.
A review study led by Dr. David A. Fishbain at the Leonard M. Miller School of Medicine at the University of Miami examined eighty-three studies that explored the relationship between the quality and extent of pain and the depths of depression among patients suffering from a variety of painful conditions (headache, spinal cord injury, cancer, angina, back pain, and so forth).
The majority of studies that tested what he calls the antecedent hypothesis—the idea that depression preceded pain—found it to be untrue, while all of the studies testing the consequence hypothesis, that depression follows pain, found it to be true. Moreover, the more severe the pain, the greater the depression. For patients who suffered from intermittent pain, the periods of depression echoed the periods of pain. The same was true of suicide: thoughts of suicide, suicide attempts, and completed suicides occurred far more frequently in those suffering from pain than in the general population and increased directly in proportion to the severity of pain.
Naturally, we might say: pain is depressing, disheartening, dispiriting. Who needs a study to understand that? But pain and depression turn out to be far more profoundly linked than is commonly understood: they are biologically entwined diseases with a common pathophysiology stemming from a common genetic vulnerability.
Chronic pain sufferers are more likely to have suffered from a depressive episode in the past and to respond to the onset of pain with a recurrence of depression. Dr. Fishbain analyzed studies that examined what he calls the scar hypothesis: that a genetic predisposition to recurrent depression is correlated with one for chronic pain. Depression is known to have a strong genetic component: sufferers frequently have family members or relatives who are or have been sufferers as well. And pain and depression are known to involve overlapping neural circuitry. Brain imaging scans reveal similar disturbances in brain chemistry in both chronic pain and depression.
There is increasing evidence that both conditions involve abnormalities in the neurotransmitters serotonin and norepinephrine, which play a role not only in mood disorders but in the gate-control mechanisms of pain. Increasing serotonin in rats engenders pain relief, while depleting serotonin increases their pain responses to electric shock. Pain decreases available serotonin (by increasing the rate at which it is reabsorbed), which weakens the pain-modulation system, creates more pain, and creates depression. Thus, we can see that anxiety and depression are not merely cognitive or affective responses to pain; they are physiologic consequences of it.
Pain causes depression just as reliably as difficulty breathing triggers panic. Thus the Nice Doctor’s decision not to prescribe opioids for Leigh because she seemed “tense” makes no more sense than “not rescuing someone who is drowning because they’re having a panic attack!” exclaimed Dr. William Breitbart, chief of the psychiatry service at Memorial Sloan-Kettering Cancer Center. “Serotonin facilitates descending analgesia” (the brain’s ability to modulate pain in the spinal cord by stopping incoming pain messages), “and chronic pain uses up serotonin, like a car running out of gas. If the pain persists long enough, everybody runs out of gas.”
Stressful events naturally enhance pain in those with a biological predisposition to it. “If we started putting sugar in the water, it would affect the diabetics first—pain patients respond to stress with increased pain,” explained Dr. Scott Fishman, who trained as a psychiatrist as well as a pain specialist. But to make stress reduction a primary strategy for pain treatment is like counseling a drowning person to relax.
“Dr. Carr finally threw me a rope,” Lee said.
OPIOID ADDICTION AND PSEUDO-ADDICTION
The misunderstandings that surround opioids have made doctors increasingly reluctant to prescribe them. In much of China and Africa, opioids are largely unavailable or prohibited. Opioids are stigmatized in the Muslim world on theological grounds; like alcohol, they are often considered a toxin that is prohibited by the Koran. Cheap opiates, such as morphine, that are no longer under patent are one of the few effective medical drugs that every country could afford. Yet the cultural acceptance of pain is such that few use these drugs. Most of the people in sub-Saharan Africa, for example, have no access to treatment for cancer (no chemotherapy, no radiation, no surgery), but if they had opioids, at least cancer sufferers could die without pain. And even in countries with high rates of infant mortality and obstetric complications, women could have access to painkillers.
In China, cultural taboos prohibit both opioids and the acknowledgment of the need for them. Decrying a nation of addicts, Mao banned opium (although he was not above growing and selling it to fund his army); today the cultural prohibition against opiates in China remains strong enough that their use is largely restricted to the elite—even for postsurgical pain. Surgeries in China are still sometimes performed using acupuncture alone, which sometimes controls pain and sometimes fails. Dr. Carr recalled observing some gruesome surgeries where the patients screamed in agony. Yet when he visited the patients in the hospital afterward, they assured him they did not suffer excessive pain during or after the operation. (Sometimes they had been given ketamine, a drug that affects memory, including memory of pain.)
Opiates are often portrayed as genies—trickster figures offering to do your bidding only in order to ultimately enslave you to theirs. Baudelaire lamented that opium was like a woman—“and like all mistresses, alas! prolific in caresses and betrayals.” But in truth, opioids are neither the snake in the garden nor the Milk of Paradise. For a variety of reasons, as will be discussed later, the drugs do more harm than good for many people with chronic pain. They are much less effective against neuropathic than acute pain. A 2003 study led by Dr. Kathleen Foley at Memorial Sloan-Kettering Cancer Center in New York City found only a 36 percent reduction in pain among patients with chronic neuropathic pain receiving high-dose opioid therapy, and only a 21 percent reduction among patients receiving the low dose.
But if opioids are less efficacious for chronic pain than commonly believed, they are also less addictive. Studies of opioid addiction vary, but a recent analysis that appeared in Pain Medicine—of twenty-four studies involving more than twenty-five hundred patients with chronic non-cancer pain on long-term opioid therapy—put the average risk of addiction at slightly above 3 percent. But for chronic pain patients with no history of addiction, the rate was extremely low (0.19 percent).
The disease of addiction usually manifests itself early, when people are first exposed to addictive substances. Patients who have no previous history of drug or alcohol abuse are unlikely to become addicted to pain drugs, especially when they are elderly. It is undeniable, however, that if doctors started prescribing more opioids, the drugs would be more widely abused because some patients would conceal addiction histories or feign pain in order to solicit drugs for resale. A 3 percent abuse rate of a widely prescribed drug translates into a lot of addicts. The question for society, then, is not, Does treating pain risk feeding addiction (because it obviously does that) but, To what extent should that risk influence pain treatment? What are the moral implications of denying opioids to patients who are likely to benefit from them?
“Are we really going to allow the fact of substance abusers to deny others pain medication?” asks Dr. Daniel Carr. “Are we going to ban alcohol because of drunk driving or ration food because some people are overweight?” In The Culture of Pain, David Morris argues that withholding pain medication is nearly
the moral equivalent of inflicting pain.
“We live in a medical society that would rather prevent one addict from being formed than treat a hundred suffering,” Dr. Scott Fishman observes. “The war on drugs hurts the war on pain.” Yet the eradication of pain is a more winnable cause.
Dr. Russell K. Portenoy, chairman of the Department of Pain Medicine and Palliative Care at Beth Israel Medical Center in New York City, pioneered the use of opioids to treat non-cancer pain. Dr. Portenoy recalls how, when he was a fellow being trained in pain management, it was widely accepted to treat cancer patients with high doses of opioids, while patients who did not have cancer but were just as disabled by chronic pain would not be offered opioids until many other treatments had failed. “Why is this treatment so accepted for one kind of pain and not the other?” he wondered.
One source of pervasive confusion about opioids lies in the difference between dependence and addiction. Everyone who takes opioids becomes physically dependent on them, such that abruptly stopping them produces withdrawal symptoms like trembling, headache, sweating, and nausea. But withdrawal symptoms can generally be avoided through gradually tapering doses. People with the disease of addiction, however, find themselves unable to taper their drug usage, not because of the unpleasant side effects of withdrawal, but because they experience an overwhelming craving. This craving differs not just in intensity but in character from ordinary withdrawal symptoms and stems from psychological, social, and genetic factors that are not fully understood.
Moreover, it requires a skilled physician to distinguish addiction from pseudo-addiction. Patients who are prescribed opioids that are inadequate to treat their pain may demand, beg, or even attempt to surreptitiously obtain more medication in a way that arouses fears of addiction in their physicians. Sometimes these behaviors lead to the patients’ having their medication terminated, when in fact they should simply have been given a different or greater prescription.
Patients who admit to prior histories of addiction are rarely prescribed opioids. Yet the abuse of drugs, including alcohol, marijuana, and even opioids, can be a misguided form of self-medication or a manifestation primarily of addiction, but nonetheless driven by the stress or discomfort associated with pain. Dr. Portenoy tells the story of an alcoholic to whom he gave the benefit of the doubt. He made the right decision, for “it turned out the patient’s pain was driving his drinking,” and when the pain was treated, he stopped drinking. But treating addicts requires greater monitoring; it is not only more time-consuming for the doctor, it is also risky. In the current political climate, in which physicians have reason to fear repercussions if a patient abuses drugs, many are increasingly unwilling to try.
Perhaps the trickiest aspect of opioids is that there is no fixed proper dose. Opioids have extraordinarily various effects on different people. Dr. Portenoy explains that while most people receiving chronic opioid therapy take a daily dose of less than 180 mg of morphine or its equivalent (such as 120 mg OxyContin), he and other pain specialists have patients who require the equivalent of more than 1,000 mg of morphine per day!
Dr. Portenoy says that many patients who take opioids have long periods of stable dosing but intermittently experience a flare-up of pain that justifies an increase in the dose to maintain pain control (the medical term for this is titrating to effect). As long as the balance between pain relief and side effects remains favorable, he argues, the new dose should be continued. Over a long period of time, these events may lead to doses gradually being adjusted upward to very high levels. Dr. Portenoy recalls a talk show he was once on, in which he asked some elderly female patients of his to join him; the elderly women explained blithely to the audience that they were taking doses of opioids that would asphyxiate a football player. “There is no ceiling dose on opioids,” Dr. Portenoy says—a concept even many physicians find difficult to grasp.
Once a person has become tolerant of the dangerous effects of an opioid, particularly respiratory depression, a high dose can be safely given. (In this respect, the side effects of opioids are unlike those of other drugs, such as Tylenol, where the liver never becomes tolerant of high doses.) If a high dose of opioids were given to an “opioid-naïve” person, it would put her in her grave (hence the high rate of deaths from accidental overdoses of recreationally used opioids, like heroin).
In 2007, guidelines for primary care physicians were issued in the state of Washington that warned them not to prescribe doses higher than 80 mg of oxycodone or OxyContin for chronic pain. Patients who required higher doses (as would be the case for most chronic pain patients) were supposed to be referred to pain specialists. Yet the same state agency offers a list of only fifteen such specialists. And—as recent prosecutions of physicians indicate—doctors who dissent have much to fear.
PROSECUTING PRESCRIBERS
The opioid backlash began in the late 1990s, when a rise in prescriptions of OxyContin led to an increase in abuse, particularly in small towns in Maine, Massachusetts, and Appalachia, where other recreational drugs were hard to come by. OxyContin is a new preparation of an old opioid, oxycodone (also used in Percocet), reformulated with a time-release mechanism designed to allow patients to avoid the typical peaks and troughs of pain relief associated with opioids, which had enslaved patients’ schedules to the drugs’ periods of peak efficacy. OxyContin’s maker, Purdue Pharma, aggressively marketed the drug to ordinary physicians, claiming that OxyContin was less subject to abuse than other opiate drugs. But this turned out not to be true: addicts quickly learned that all they had to do to get high was to crush the tablets to destroy the time-release mechanism and then snort or inject the powder.
During the George W. Bush administration, the Drug Enforcement Administration (DEA) expanded the war on drugs by creating an action plan on OxyContin. Purdue was prosecuted, the company and its top executives pleaded guilty to misrepresenting their product and misleading physicians, and Purdue paid more than $600 million in fines. For the DEA, the addicts—often kids filching pills from their parents’ medicine cabinets—were petty targets. But the prescribing physicians were not; if a criminal case is brought against a doctor, the DEA and local investigators are entitled to seize the physician’s assets (on the grounds that they are drug profits). Moreover, the addicts could be compensated for their cooperation: if a physician is convicted in a criminal court, his or her patients may be able to win a civil case (with a lower standard of proof) against the physician for feeding their addictions!
It takes only a few lawsuits—or simply the threat of DEA oversight and regulation—to exert a chilling effect on prescribing practices. “Doctors feel damned if they do and damned if they don’t,” commented Dr. Scott Fishman. One day, brain imaging may develop to the point of being able to provide objective documentation of pain for each patient. But at the moment, a doctor can always be fooled by a patient who is feigning pain in order to misuse drugs. “You have to be willing to make mistakes,” Dr. Carr said, “and you have to accept that some patients will take advantage of you, and your feelings will get hurt.”
Hurt feelings are one thing; the threat of imprisonment is quite another. Of course there have always been physicians who actually are drug dealers—who sell prescriptions for money or sex and are appropriate targets for criminal indictments. But never before have physicians been held responsible for drug abuse that they did not know about or profit from.
The case of Dr. Ronald McIver, a sixty-five-year-old South Carolina pain specialist who received a thirty-year sentence for drug trafficking in 2005, is particularly striking. The government based its prosecution on a few patients who feigned pain to get prescriptions because they were addicted or wanted to sell the drugs. Dr. McIver took the precaution of requiring his patients to sign an opioids contract, stating, among other restrictions, that they would not ask for early refills of the medication and would bring their pills in at each appointment to show that they had the right number left. He became suspicious of two of his patients
(one of whom he stopped treating after the patient altered a prescription to get an early refill) and wrote a letter to the state’s Bureau of Drug Control asking them to investigate. Instead the DEA later used his letter as proof that he had knowledge of the diversion of pills he had prescribed!
After the verdict, for an article in The New York Times Magazine, Tina Rosenberg interviewed jury members who told her that they felt the dosing levels were too high. One juror thought his sister-in-law had become addicted to pain pills; another said that she had once been given opioids for a minor ailment, so she believed she knew what a standard dose was and Dr. McIver’s dose was too high. None of the jurors appeared to grasp the idea that there is no ceiling dose for opioids. Still, they seemed shocked to find out that Dr. McIver had been sentenced to thirty years in prison (since they were not part of the sentencing phase of the case).
Since Dr. McIver did not profit from his patients’ drug trafficking, the prosecutors had to come up with a motive to prove their contention that he intentionally prescribed drugs he knew would not be used for pain treatment. They proposed that he prescribed the drugs so that the patients would come to his office and then he could bill them for other treatments, such as injections and chiropractic adjustments. The fact that Dr. McIver’s income was unusually low for a physician (indeed, his previous practice had ended in bankruptcy), because the procedures he performed were not, in fact, lucrative and he typically spent a full hour or more with patients, did not sway the jury.
Dr. McIver stated that his goal was to reduce his patients’ pain to a 2 on a 10-point scale (with 10 representing the worst pain the patient can imagine) so that his patients could return to their previous levels of activity. The pain specialist who served as the government’s expert witness at Dr. McIver’s trial testified that he personally believed that 5 was a more reasonable goal. I wonder if the expert witness revealed to his own patients that he would be content to leave them halfway to the worst pain they could imagine. Had the expert witness ever experienced pain? Would he want to be cared for by a doctor who shared his philosophy?
The Pain Chronicles Page 16
