Richard Smith reviews Empire of Pain: The Secret History of the Sackler Dynasty and concludes that the US opioid epidemic could not have happened without doctors and the whole medical establishment playing a part

The half a million and still rising deaths from opioid overdoses in the US, together with increasing numbers in other countries, is surely medicine’s biggest failure. I tried to think of what might match it. The mass incarceration and abuse of people who are mentally ill over centuries? The infection of patients with hepatitis B and HIV? The deaths and suffering that result from 10% of all patients admitted to hospital suffering an adverse event and 1% dying? The torturing of the dying? The many unnecessary operations? The widespread overtreatment? Healthcare’s considerable contribution to ecological disaster and climate change? Ivan Illich would say the destruction of cultural mechanisms for responding to the suffering, pain, death, and grief that are part of being human, but the burgeoning epidemic of deaths from opioids must rank high.

Patrick Radden Keefe tells an important part of the story of the epidemic in his magnificent book, Empire of Pain: The Secret History of the Sackler Dynasty, a family saga that reads like a great novel, reminding me of Thomas Mann’s Buddenbrooks and Elizabeth Jane Howard’s Cazalet Chronicles. The book convincingly makes the case for the greed of the Sackler family being the main driver of the epidemic, and from the beginning of the book you are fascinated to know if the family will get the punishment it deserves. The answer is essentially no legally, but yes in terms of reputation. No Sackler has been to prison, and they still have their billions—but their name is disgraced and removed from art galleries, museums, and universities.

At the end of his book Keefe acknowledges that blame for the crisis could also be made against other pharmaceutical companies, the US Food and Drug Administration, “the doctors who wrote prescriptions, the wholesalers that distributed the opioids, and the pharmacies that filled the prescriptions.” There are other books to be written about the role of these different players, and I look forward particularly to reading the one on the role of doctors and the whole medical establishment. Some of the elements of that book can be extracted from Keefe’s book, and that’s what I want to do in this article. But first I want to summarise the role of the Sacklers and their drug company Purdue.

The family saga begins with the three Sackler brothers Arthur, Mortimer, and Raymond, who were born in Brooklyn between 1913 and 1920. The family, particularly Arthur, had the entrepreneurial energy and drive of immigrants, and all three sons overcame poverty to graduate as doctors.

Arthur, who died in 1987 before the opioid epidemic began, was in many ways brilliant and invented much of the pharmaceutical marketing that has become so familiar: glossy rather than sober advertising; drug representatives performance managed to sell; hiring doctors to promote drugs (key opinion leaders or KOLs in the jargon); dubious scientific studies that exaggerate the problem, downplay side effects, and advocate new conditions for which the drugs will work; free trips for doctors; conferences featuring well paid speakers; medical newspapers filled with promotional material; incestuous relationships with regulators; and databases that identify high prescribing doctors. His achievements earned him a place in the Medical Advertising Hall of Fame.

The Sackler brothers owned a medical advertising company (and secretly its main competitor), a medical newspaper, and a database company. They used this formidable marketing capacity to power the sales of Librium then Valium, asserting that the drugs were effective in a huge range of conditions, had no side effects, and were not addictive. It was their success in peddling these minor tranquillisers that made them the millions that they began to give to museums, art galleries, and universities, always insisting that their family name was attached. From the beginning they were adept, in contrast, at separating the family name from their ever proliferating companies.

The logical next step was for the family to buy a pharmaceutical company, which they did in 1952. Purdue Pharma was a sleepy company selling laxatives, but the Sacklers longed to create a company with a “blockbuster,” a drug that makes billions. Eventually they came up with the idea of a controlled-release opioid: MS Contin containing morphine was released in1984 and Oxycontin containing the more powerful oxycodone in 1996. Purdue Pharma argued that these controlled-release formulations were not addictive because there were no peaks and troughs—the cause, they argued, of addiction. Fewer than 1% of those taking the drugs became addicted, according to the company, and those who did become addicted did so because they were prone to addiction not because the drugs themselves were addictive. This, as Keefe points out, is the same argument as that used by the gun lobby—the people, not the guns (or drugs), are the problem.

Purdue Pharma used all the tactics developed by Arthur to market the drugs, including publishing studies on the high prevalence of chronic pain and targeting deprived communities where the prevalence was especially high. Somehow the Sacklers and the many leading doctors who worked with them managed to shift medical thinking in the US to regard opioids as essentially non-addictive and suitable for treating non-malignant pain. That was a remarkable achievement and, as far as I can tell, has not happened in Britain. The result of the marketing was a rapid rise in prescriptions, soon followed by a rapid rise in deaths that resulted from both use and abuse of the drugs and addicted people moving to illegal opioids.

Much of Keefe’s book is devoted to the proliferation of legal cases against the company and eventually the family. The family has always refused to accept that they have done anything wrong and, by Keefe’s account, have used high charging lawyers and political connections to avoid justice. None of the family would talk to Keefe when he was writing his book, and they tried to stop the book.

All three of the Sackler brothers were doctors, and several of the later generations also trained as doctors, although few of them saw patients. They had great respect for the medical profession, and Arthur was comfortable with the doublethink that allowed him to see the success of his marketing and at the same time argue that “doctors were unimpeachable.” “It was laughable,” he asserted, “to suggest that a physician might be seduced by a glossy layout in a medical journal in the same manner that a housewife might be swayed by a slick ad in a magazine.” (Such sexism was, of course, normal at the time.) Yet, as Keefe quotes: “The doctor is feted and courted by drug companies with the ardor of a spring love affair…The industry covets his soul and his prescription pad because he is in a unique economic position; he tells the consumer what to buy.”

The epidemic of opioid deaths could never have happened without doctors prescribing the drugs in large amounts. Some doctors were clearly culpable in that they ran “pill mills,” where they prescribed huge quantities of drugs to anybody, knowing that many of the drugs would find their way onto the black market. Many of those doctors went to prison, but just as gambling companies make much of their profits from addicted gamblers so Purdue made much of its profits from these “pill mills” and from the “high prescribing” doctors, who weren’t doing anything illegal but were not practising good medicine. These doctors were known as “whales” to the salespeople.

Crucially important in stoking the opioid epidemic were the leading doctors who promoted MS Contin and Oxycontin. Purdue funded many such doctors, and often they spoke to other doctors in expensive resorts where the attending doctors had all their expenses paid. One doctor, Russell Portenoy, a neurologist who was called “the King of Pain,” argued (not incorrectly) that the medical establishment had not taken pain seriously. Opioids were, he said, a “gift from nature” and he co-authored an influential paper that highlighted “the possibility of long-term pain relief from opioid therapy, without the development of . . . serious adverse effects, including drug abuse.” He also spoke at a conference at the University of Toronto organised by Purdue where many doctors preached the benefits of treatment and downplayed the risk of addiction. 

David Haddox, a pain doctor, was employed by Purdue and a strong advocate of the wider use of MS Contin and Oxycontin. He advanced the argument that problems arose not from the drugs but from the patients: “If I gave you a stalk of celery and you ate that, it would be healthy. But if you put it in a blender and tried to shoot it into your veins, it would not be good.” Haddox developed the concept of “pseudo-addiction,” which “seems similar to addiction, but is due to unrelieved pain.” The treatment he advocated was to increase the dose of opioid.

The New England Journal of Medicine features in this sorry saga. It carried many of the ads for Librium and Valium produced by Arthur’s company and was, Keefe says, making “more than $2 million a year” in the late 60s (about $15m in 2021) from advertising, most of it from drug companies. Much more troublesome is a seven line letter published in the journal in 1980 headed “Addiction Rare in Patients Treated with Narcotics.” The letter was used extensively by the drug reps of Purdue, and their sales materials summarised the study as saying “a survey of more than 11 000 opioid-using patients, taken over several years, found only four cases of documented addiction.” The drugs reps must as well have quoted the last sentence of the letter, which reads: “We conclude that despite widespread use of narcotic drugs in hospitals, the development of addiction is rare in medical patients with no history of addiction.” This plays to the idea popular with those at Purdue Pharma that the only people who become addicted are those who are prone to addiction.

The New England Journal of Medicine has come under pressure to retract the letter but has not done so. Instead, it has attached to the letter: “‘Editor’s Note’ (added May 31, 2017): For reasons of public health, readers should be aware that this letter has been ‘heavily and uncritically cited’ as evidence that addiction is rare with opioid therapy. Leung et al. describe its history.” The letter by Leung et al analyses 608 citations of the letter and shows that most (72%) cited it as evidence that addiction was rare in patients treated with opioids. The authors also analysed the citations over time and classified them as affirmative (supporting the conclusion that addiction is rare), negative, or other. The citations peaked in 1996, the year Oxycontin was launched, and were almost all positive with no negative citations. Indeed, there were no negative citations until 1999, when there was one.

I’m sure that the editors of the journal published the letter in good faith, but a combination of the prestige of the journal, its high circulation among American doctors, and particularly the extensive use of the letter by the drug reps of Purdue must have played a prominent part in the change of attitude towards opioids among the medical establishment.

Doctors, unlike pharmaceutical companies, tend to get a positive press: they are the “good guys.” But the catastrophe that has struck the US could not have happened without doctors prescribing the opioids and prominent doctors and journals promoting them. 

Doctors and the healthcare system have probably not matched SARS-CoV-2 with the deaths and suffering they have caused, but if we were to add to the deaths and suffering caused by the opioid crisis the others caused by doctors and the healthcare system that I listed in the first paragraph they might come close. And the harm from SARS-CoV-2 will eventually dwindle away whereas the harm from doctors and healthcare continues.

Richard Smith was the editor of The BMJ until 2004.

Competing interests: none declared.