The title of this article originates in the 1821 drug memoir of Thomas De Quincey, who at age nineteen (in 1804) became addicted to Laudanum, a preparation of opium dissolved in alcohol prescribed for rheumatic pain. In his Confessions of an English Opium-Eater, he wrote, “Oh, heavens! what a revulsion! what an upheaving, from its lowest depths, of inner spirit! what an apocalypse of the world within me!” (33). Although De Quincey began his opium habit to relieve pain, drug-induced euphoria transformed him into a recreational user. As he fell into addiction, he began to suffer cycles of intolerable intoxication and physical misery, particularly stomach agony.
This article evaluates the current opioid overdose crisis in the United States through the eyes of a physician. This epidemic has become so severe in recent years that it has led to a decrease in average life expectancy. It has produced more annual fatalities than those attributed to suicide or homicide, to recent wars, or to epidemics involving infectious agents. In 2019, the number of opioid-related fatalities will likely reach 50,000, the same as the number of AIDS-related deaths in the peak year of that epidemic in 1995. During the past fifteen years, more than 200,000 Americans have died of opioid overdoses. About one-fifth of this group once suffered from chronic pain (and most likely addiction complications) that doctors usually treat in office settings. Statistical evidence shows that since 2012 there has been a slow but steady decline in opioid prescription, explained partly by doctors resisting the pressure of patient demands for relief of pain (CDC 2019). Psychiatrists were hopeful that this trend and the recent success of skilled intervention applied to groups of vulnerable persons signaled an end to this crisis, but the national overdose death toll has not declined during this period, probably because of large increases in heroin and fentanyl use (Madras 2017).
I must confess that my own efforts have been bedeviled by unexpected thorny limitations and complications. We physicians were not fully aware of the new problems created by broad solutions and failed to sufficiently recognize the individual vulnerabilities of unique patients. This article explores the misunderstanding.
First, we should remember that opioids have successfully alleviated severe pain for thousands of years (Offit 2017); sometimes there are also mood benefits. I prescribed buprenorphine as a last resort to help a forty-year-old patient, a stockbroker who suffered from a severe suicidal depressive disorder. He had recently terminated twenty years of unsuccessful psychoanalysis. Conventional antidepressant medication management was of no help either. Usually happy in a long marriage, he lost sexual interest in his partner and felt constantly helpless and despondent. Ordinarily trifling self-esteem challenges were interpreted as catastrophes, and he made major mistakes in his business dealings. The extraordinary severity of symptoms merited a different treatment approach—opiates. To the surprise of both of us, he has experienced relief of major depressive symptoms for the past ten years while continuing to take moderate amounts of buprenorphine and has not developed tolerance to the medicine. At least in some circumstances, opioids do have benefits beyond relief of physical suffering.
For readers who are not medical specialists, I will review salient details of the current science of opioids. These biochemical neuropeptide substances can nullify pain and alter moods, including depression. They are almost always addicting and lead to higher doses over time because of consequent states of euphoria, transitory well-being, and even grandiosity. As documented above, deaths are caused by overdoses. Opioid effects mimic beta endorphins, substances naturally occurring in the human body. These exert their biochemical, medical, and mind-altering influence at so-called “Mu receptor sites” in the body that are selectively responsive to their stimulation. When exposed to medicinal or recreational long-term use of high-dose opioids that generate addiction, neural structures sensitive to beta endorphins can suffer damage that is difficult to undo or reverse.
Most of the chemicals involved with the current opioid crisis are natural opiates found in the resin of the opium poppy, papaver somniferum. They include about two dozen alkaloids, of which morphine and codeine are the most familiar pain remedies. A number of other common opioids might be familiar to readers. The semi-synthetic opioids hydrocodone, hydromorphone, oxycodone, oxymorphone, and codeine are also chemically modified derivatives of the poppy plant. Fully synthetic drugs such as Darvon (propoxyphene) and Demerol (meperidine) are slightly more potent pain remedies. Oxycontin is a slow-release form of oxycodone and is a modification of the opiate alkaloid thebaine (paramorphine) found in opium. This medicine has been proven highly addictive and is often fatal in uncontrolled doses. Its manufacturer, Purdue Corporation, has paid almost a billion dollars in legal penalties because of misleading marketing. Tramadol is a synthetic non-opioid agent that is a weak analgesic rarely causing dependence.
The seedpod of the opium poppy plant, modified by a half-dozen common chemicals, is also the source of heroin. This notorious, illegal-today drug was first produced in 1898 in Germany and offered as a safe “wonder” medicine for cough and pain. The inventor, Heinrich Dreser, developed an easily reproducible process of acetylation of morphine that enormously elevates its potency—heroin is about fifty times as powerful as morphine. Heroin dependence often starts with routine office remedies for pain, and it is estimated that as many as 80 percent of heroin users started their addiction with prescription opioids (Compton et al. 2016). Even more dangerous than heroin are synthetic substances such as fentanyl and carfentanil, a drug used to tranquillize elephants. Fentanyl is fifty to 100 times more potent than morphine; more often than heroin, it kills many addicted persons who lived for years while routinely using less-potent opioid drugs (Mather 1983). It was responsible for over a third of the 72,000 U.S. overdose deaths in 2017 (NIH 2019). It is critical to remember that opioid-misuse death only rarely takes place secondary to a single drug. Cocaine, amphetamines, alcohol, or benzodiazepines almost always complicate the clinical opioid danger (Seth et al. 2018). This danger severely limits the outcome of even the best outpatient addiction and pain treatment efforts directed primarily toward opioids.
Roughly 60 percent of older Americans on Medicaid have been reported to have chronic non-cancer-related pain (Olfson et al. 2017). This aged population is heavily afflicted by opioid dependence, and its members frequently have an accompanying diagnosis of an opioid-use disorder. Research on other large populations such as U.S. Department of Veterans Affairs (VA) patients (Bohnert et al. 2011), jail and prison inmates (Troilo 2018), and large groups of Florida’s inhabitants who were prescribed opioids in outpatient and inpatient settings identified in official morbidity-mortality reports (Florida Department of Law Enforcement 2017) all point to significant opioid dependence in older Americans. On the basis of the best available research I could identify, this past year I compared three major possible intervention strategies for such populations (Barglow 2018). I included data and commentaries from outcome reports of large treatment efforts to lower fatality rates for drug-addicted patients in several European countries, the Philippines, and China. Each intervention type has been found to have clear advantages, risks, and dangers. All three have major expert advocates as well as equally persuasive scholar opponents.
A demand reduction strategy responds to the difficulty of curtailing access to opioids by modifying the human motivations that result in overuse. The urgent demand for relief of suffering is counteracted by “behavioral immunity” induced through forcefully enhancing risk aversion. The stigma of addiction, illustrated for example by derogative terms to describe addicts, triggers shame and keeps many patients from seeking treatment. But it has not become a major deterrent to drug overuse. Junkie zombie was the term for stumbling addicts in the early twentieth century who supported their habit by collecting and selling scrap metal. Less colorful terms such as dope fiend, stoner, pothead, street addict, and dirt are still widely used today, even by some members of the addiction-treatment community. Urine tests showing the presence of illegal drugs are still customarily labeled “dirty” while a “clean” sample is negative for drugs. These pejorative images fuel widespread public opposition to efforts to ameliorate opioid overdose risks. For example, legalization of needle-exchange sites to provide clean needles is vociferously opposed, despite evidence showing that such publically designated areas are proven to reduce overdose risk and disease transmission.
Pain-relief treatment using opioids varies across geographic locations in the United States. Nearly 10 percent of adults in rural settings receive opioid prescriptions—about twice as many as in large metropolitan counties (Garcia et al. 2019). On an international scale, countries differ massively in the amounts of opioids consumed. American opioid use is many times higher than that in other developed countries; Americans consume almost all the world’s production of hydrocodone and similar agents. Variations in cultural attitudes and history across these different locations play a crucial role in generating tolerance to emotional or physical pain, with differences often expressed by capacity to tolerate suffering or exhibit a kind of stoicism. Thus physicians in Japan prescribe opioids for pain relief much less often, and in smaller doses, than American physicians do. Few contemporary experts believe that use of addictive drugs involves very much choice (Angell 2019). Libertarian scholars and journals with their traditional belief in free will have been the most fervent advocates of the demand reduction approach. But the persistent lethal toll of opioids over many years, along with scientific findings, has converted many of their healthcare scholars to acceptance of supply-limitation and legal remedies (Hart 2017).
A supply reduction strategy attempts to decrease the availability of addictive drugs. This approach targets the supply of high-potency medications such as fentanyl and illegal agents such as heroin. Considerable evidence prior to 2012 indicated that high prescription dosage levels were directly related to opioid overuse death. However, even tight regulation efforts do not always succeed, as shown by Florida’s efforts to restrict prescription of these substances (Florida Department of Law Enforcement 2017).
The problem with this approach is that draconian restriction of opioid access driven by moral condemnation can have its own harmful effects. In a study of a large VA health system, I found that between 1993 and 1998, twenty-two of fifty-three officially reported suicides were opioid overdose deaths. Most in this group of patients perished after ill-advised efforts to rapidly detoxify from opioid prescribed agents (such as methadone) for pain or addiction (Barglow 2004). It is certainly true that some persons simply cannot survive prolonged opioid use, and in these instances the supply must be zero. One of my patients was eighteen years old and diagnosed with a bipolar disorder. For him even tiny amounts of opioid inevitably triggered a dangerous mood swing; here, zero tolerance was mandated. In general, however, abrupt and complete restrictions on opioid use can be very dangerous.
Given the frequent inadequacy of traditional supply limitation methods, imprisonment is the most common solution mandated by both American law enforcement agencies and many influential political leaders. Forced separation of a drug-dependent prison group from their habitual drug agents has high success during incarceration but a dismal record of abstinence after discharge (Binswanger et al. 2013). Concerns about racial injustice profiling of black Americans have motivated some scholars to avoid harsh curtailment of drug availability. Black criminals historically and currently are more likely to be incarcerated for longer periods of time than white criminals. Early in the opioid overdose epidemic, public attention and funding for treatment was assigned primarily to Caucasian populations. However, in 2017 black victims made up 12 percent of overdose deaths (twice the number of 2015), many involving fentanyl. Opioid overdose deaths in this ethnic group might have been overlooked within the U.S. penal system (James and Jordan 2018). Black scholars and researchers tend to be especially loath to advocate for harsh forced supply reduction interventions requiring imprisonment for long periods. Incarceration treatment proposals find much opposition in Native American communities as well (Shihipar 2019).
A harm reduction perspective maintains that abstinence might not be realistic for many users. Too rapid or sharp a dose reduction can actually increase the social, psychological, and medical damage of addictive substances. This approach informs policies, programs, and practices that attempt to reduce the negative consequences of sustained drug use. Originating in Australia, the United Kingdom, and the Netherlands in the early 1990s, this kind of intervention was initially designed to impede the spread of AIDS among injection drug users. Harm reduction focuses on reducing the consequences of opioid misuse through effective treatment, promotion of safe-use practices such as needle exchanges, substitution of lower-risk medications such as methadone or buprenorphine, and provision of opioid antagonists such as naltrexone or naloxone.
A major challenge to this strategy is that the natural human opioid system is also a common pathway for antidepressant effects, including natural and placebo responses. Many pain sufferers are also quite depressed. The use of a potent drug to reverse or avoid opioid overdose, such as naltrexone, therefore may nullify antidepressant medicine capacities such as those of the promising new drug ketamine (Heifets et al. 2018). In addition, these methods are all quite expensive. Dr. Marcia Angell, a former editor of the New England Journal of Medicine, has been particularly active in efforts to allocate the funding to enable optimal use of this approach. In her recent review article about opioids, she writes, “Economic misery resulting from ‘grotesque inequality’ in America is responsible for ‘deaths of despair’” (Angell 2019, 18).
From 2000 to 2010, one-fifth of U.S. patients with non-cancer-related pain were prescribed opioids in an outpatient office setting. The major recent difference in my own practice is my effort to reduce the danger of opioids for pain through prescribing methadone or buprenorphine. These medications are synthetically produced therapeutic substitute opioids, which are now very widely prescribed in the United States. Substituting them for more potent opioids assists weaning patients off of heroin and other opioid agents. Buprenorphine is safer than methadone because it produces minimal euphoria, interferes little with cognitive functioning, and minimally jeopardizes respiration. Neither agent produces overdoses if used without co-drugs and under supervision of medical specialists. But to cease their use or to diminish dosage is difficult for most persons.
A patient of mine—a teacher, wife, and mother of three thriving children—had steadily reduced her buprenorphine dose. The medication had replaced addiction to large amounts of hydrocodone initiated after minor heart surgery. Beginning at 20 mg/day, after six months she was taking only 8 mg/day. However, she had saved the unused tablets (which I failed to collect). Unexpectedly, one day during a psychotherapy session she announced, “Doctor, I had to go back up to 20 mg of my medicine.” “Why?” I inquired. It turned out that her uncle planned to divorce, and this news was “terribly distressing.” So a trivial incident had triggered relapse to a much higher dose. Alas, patients rarely are able to cease use of such substitute therapeutic agents. For me, this reduction failure is a warning that Epidiolex, an FDA-approved marijuana substitute medicine (June 2018 for treatment of convulsions in children), will likely not ameliorate the opioid overdose crisis.
Mistakes in using any of the above three interventions may provoke suicidal depression, all-pervasive obsession with drugs, or distressing withdrawal symptoms. The research of Krebs et al. (2018) even claimed—mistakenly—that there was little benefit from opioids for chronic orthopedic pain. Like most doctors, I have been under heavy social and political pressure to not overprescribe opioids. But I am more convinced by the arguments against severe curtailment of pain medication voiced by so many patients and their advocates (Leonhardt 2019).
In conclusion, we must remain skeptical of most contemporary generalizations about ending opioid overdose risks. Awareness by the public of their limitations and constant reminders to physicians that they must flexibly individualize pain and addiction treatment are vital. Experts are no longer as baffled by opium’s influence as De Quincey was two centuries ago. Still there is much more we can learn from further clinical research studies.
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