The Sacklers paid little attention to the developments about Ebola or the scattered accounts of unexplained illnesses afflicting visitors to Africa. As doctors, they were naturally interested in the emergence of any new pathogen, but that was tempered by the knowledge that it did not present them any business opportunity. Purdue never had a product targeting infectious diseases. The immense research costs had made that field the province of much larger drug firms. Even Arthur’s big pharma clients had shifted their scientists away from antibiotics and to new, more profitable classes of medications that targeted chronic diseases.
In 1978, the Sacklers rolled out Napp Chemicals in the U.S. and Pharma Technologies in the U.K. (no family member was listed as an owner on the incorporation papers).1 The following year, they opened Mundipharma in Germany, the tenth country for the Mundi brand since its launch in Switzerland in 1957.I2
While Mortimer and Raymond worked on the family’s pharma components, Arthur was busy helping Roche scramble to figure out how to reverse the first ever drop in Valium sales.3 Arthur was, as his brothers and colleagues knew, a blunt realist when it came to business. He did not sugarcoat Valium’s prospects to Roche. Its past success was now part of its problem. An estimated 20 percent of all American adult women were regular users. Although revenue had declined in 1976, almost two billion pills had been prescribed.4 Even without the Controlled Substances Act restrictions and the FDA limits, he contended, Valium had so saturated the market that it might be nearing its natural maximum penetration.5
Since there were still eight years left on Valium’s patent, Sackler said, it would be foolish not to make every effort to stop it from slipping further. The upside to the aura around Valium meant it had crossed into popular culture and had a hold on the American psyche. It was, according to one medical writer, “one of the most praised drugs in history and one of the most maligned.”6 A decade after the Rolling Stones had sung about it, there were references to the drug in Neil Simon plays and Woody Allen films. A group of Upper East Side New Yorkers dubbed themselves the Valium Girls Club. Comedian Rodney Dangerfield boasted it was part of his daily regimen.
Valium’s high profile also worked to its detriment whenever it figured in any much publicized story of celebrity addiction or overdose. Elizabeth Taylor admitted she was addicted to Valium and Jack Daniel’s. Tammy Faye Bakker, half of an evangelical empire, claimed her reckless financial decisions were the result of her daily affection for a customized Valium nasal spray. Television producer Barbara Gordon’s harrowing story of how she landed in a mental asylum after quitting Valium cold turkey became a best-selling book.7
When forty-two-year-old Elvis Presley died in August 1977, his autopsy was a toxicological snapshot of the era’s most abused drugs: Valium was mixed with “significant” quantities of codeine, Quaaludes, Ethinamate, a popular sedative-hypnotic, and a barbiturate never confirmed but reportedly phenobarbital. He also had painkillers Demerol and morphine, another tranquilizer, Placidyl, and the antihistamine Chlorpheniramine.8II
Valium’s sales stumbled. It was an opportunity for competitors to introduce new benzodiazepines they claimed had all of its benefits without the downsides. Arthur knew that Roche had a “better and improved” product, Klonopin (clonazepam). It was one of the “backup benzos” developed by Leo Sternbach, the scientist who had discovered Librium and Valium. Roche had patented it in 1964 and put it on the shelf. After Roche had both Librium and Valium on the market within three years of each other, it held back on releasing Klonopin for fear of cannibalizing the big sales of its first two benzos. With Valium under increasing attack, however, Roche agreed with Sackler. Thirteen years after the drug’s discovery, Roche set aside $20 million for a national rollout of Klonopin in the U.S.9
Its release made other drug companies rush their competing benzos to market. Wyeth released Ativan in September 1977. It was a versatile benzo that was effective for insomnia, anxiety, and seizures. One dosing advantage it touted over Valium was a much shorter half-life, reducing the hangover effect about which some patients complained.10 Warner Lambert followed in a month with Prazepam, another short-acting, antianxiety benzo.
Sackler adjusted Valium’s advertising strategy. Data gathered by IMS showed that doctors were more inclined to write prescriptions for a premium pharmaceutical firm they judged to be at the forefront of research and development of a drug category.11 As a result, Roche emphasized Valium’s long history and the millions of case studies that demonstrated how safe and effective it was when used correctly. Did physicians want to gamble with their patients’ health by dispensing newcomers that looked good in clinical trials but had little real-world experience?12
Valium sold a record 2.3 billion tablets the following year, 1978.13 It became the first drug in the history of the pharmaceutical industry to surpass a billion dollars in accumulated sales.14 That was the same year former first lady Betty Ford checked herself into rehab for an alcohol and Valium addiction.15 Senator Ted Kennedy announced hearings before his Health Subcommittee to address the “nightmare of dependence” Valium had created for millions of Americans.16 III 17
Sackler, however, could not rescue Valium. It was not ultimately possible to reverse the “health risk” story line that had reshaped the public’s perception. He managed to delay its final reckoning, though. By 1980, Valium’s annual prescriptions had fallen in half to 30 million. That was still enough to keep it in the top ten selling prescription drugs in America. Arthur had told Roche executives that if they wanted to revive the glory days when their benzos dominated the mild tranquilizers, the answer was to be found in their own labs.18 Roche had hoped Klonopin might be the replacement but it did not have Valium’s blockbuster appeal.
There were a couple of benzos in the FDA pipeline that Sackler thought were commercially very promising, but neither was a Roche product. Both were from Upjohn Laboratories in Kalamazoo, Michigan. Upjohn thought it had developed a Valium killer in a benzo it named Halcion.19 It was fast acting and left no hangover. In small doses it was a good sedative and in higher strengths acted as a hypnotic tranquilizer. Upjohn submitted it to the FDA for approval in May 1976, as the tide against Valium was under way. The FDA review office had concerns about some efficacy claims but mostly about some adverse effects, including mental confusion, amnesia, and rebound insomnia in which abrupt discontinuation of a drug worsens a patient’s sleeping problems.20 Although the FDA’s Psychopharmacologic Agents Advisory Committee recommended in 1977 that it be approved for sale, the FDA decided to order additional clinical testing. Halcion would not get approved for another five years (November 1982).
Upjohn had another drug, alprazolam, on which it had obtained a patent in 1971. It had intended to market it originally as a sleep aid. Additional clinical trials showed it was also effective in reducing anxiety, had promise as an antidepressant, and reduced panic attacks. Upjohn submitted the drug to the FDA only after Halcion’s delay. And to Upjohn’s surprise, in November 1981, alprazolam got approved while Halcion was still undergoing more testing. Upjohn put alprazolam on the market under the brand name Xanax.21
Arthur Sackler had been right. Valium’s final denouement would not be because its large base of loyal patients became skittish about it; he had predicted they would leave for a medication they perceived as better. Xanax was a hit. As with Halcion, Xanax also metabolized in the body in about half the time required of Valium. Upjohn promoted it as the benzo that would not leave patients drowsy the next day. They also got lucky on another front. A year before the FDA gave Xanax a green light, the third edition of the DSM (Diagnostic and Statistical Manual)—the bible for diagnosing and treating psychiatric disorders—added “panic disorder” for the first time.22 It was the first update of the DSM since 1968.
Although most researchers assumed that the other benzos—Librium, Valium, Klonopin—would probably be just as good in treating panic disorders, Upjohn was the only firm that had tested their drug for that condition and demonstrated its effectiveness.23 When the FDA approved Xanax as the first ever drug to treat the disorder, some competitors sarcastically dubbed it “the Upjohn illness.” No pharma rival underestimated the achievement in formally medicalizing panic disorder.24 Xanax sales skyrocketed.25 Into the mid-1990s, Xanax alone provided about a quarter of Upjohn’s worldwide sales; that was no small feat considering it also had three other commercially successful drugs in unrelated categories.26 IV 27
Upjohn had done more than create the drug that knocked Valium off its pedestal; by converting a DSM anxiety diagnosis and getting FDA approval for a biological solution on which it had a patent, it set the template rivals would follow. The 1980 edition of the DSM, which some Freudian psychiatrists criticized as “capitulation to computers and insurance company requirements,” increased the number of recognized mental illnesses from 182 to 265.28 A much wider range of emotional complaints suddenly seemed to have a DSM listing, making them subject to insurance coverage. Harvard psychiatric professor Arthur Kleinman thought the new DSM belittled the misery of people with serious mental illnesses at the cost of “medicalizing ordinary unhappiness.”29 Author and psychiatrist Peter Kramer dubbed it “diagnostic bracket creep.”30
The DSM III separated depression from anxiety. It then provided a list of separate stand-alone mental illnesses under anxiety. It put Upjohn’s panic disorder alongside generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), social phobias (SAD), and post-traumatic stress disorder (PTSD).
Vietnam vets and their advocates had lobbied hard for the inclusion of PTSD. A leading mental health journal estimated that upward of 700,000 of the three million who served in Vietnam had the disorder.31 A later federal study thought the real number of vets suffering from PTSD was closer to 1.5 million, 85 percent of whom had been in combat. In a couple of years, PTSD was an increasingly common diagnosis for victims of domestic violence, rape, and child abuse.
Several pharmaceutical firms launched research to develop drugs that treated the new mental disorders in the DSM. By the end of the decade, some of the most dramatic results would be evident with the introduction of Prozac, a new class of antianxiety and antidepressant medications called serotonin reuptake inhibitors.
America’s love-hate relationship with Valium was never more evident than in two quite different events in 1982. The inventor of the benzodiazepine class, Leo Sternbach, won the John Scott Legacy Medal for his pioneering work. That prestigious award, presented annually since 1816, is for an invention that “enhanced the comfort, welfare, and happiness of humankind.” Previous winners included Marie Curie, Jonas Salk, Thomas Edison, and Nikola Tesla. At the same time Sternbach got that accolade, Ralph Nader’s Health Research Group published Stopping Valium, a searing indictment that claimed Valium and its chemical cousins in the benzo class were responsible for an “unparalleled addiction and health crisis.”32
Arthur Sackler found nothing incongruous about the Sternbach award and the Nader broadside. Nader focused on the worst statistics and assigned blame widely, all part of expanding his influence as a consummate consumer advocate. Nader and others blamed the pharmaceutical companies for discovering and then aggressively marketing their drugs. The more successful a drug, the more blame it got. In Sackler’s view that was too simplistic. He agreed with Sternbach, who was asked by a reporter if he would have changed the drug were it possible to go back in time? “I can’t get the feeling to be responsible for the drug’s use. I’m responsible for the class of compounds.… But for its use, I mean, everything can be abused. So you cannot create things that will be abuse proof.”33
Arthur clipped Gilbert Cant’s famous New York Times Magazine 1976 cover story titled “Valiumania” The final paragraph read, “If Valium is a major reliance in what moralists and some sociologists complain is a hedonistic, sybaritic culture, losing its git-up-’n’-git-drive and seeking nirvana in a little bottle of tablets, its use is a symptom rather than a cause of this condition. Properly used by the medical profession, it has only medicinal properties. A drug has no moral or immoral qualities. These are the monopoly of the user or abuser.” Arthur underlined the last two sentences. It not only applied to Valium, Sackler thought, but was true about drugs in general.34
I. In 1978 one of the family’s longest-serving attorneys, Martin Greene, opened a solo practice. The New York State Bar Association listed his address as 15 East 62nd Street in Manhattan and his telephone number as (212) 832 7900. That was the same address and number as a number of new Sackler-owned companies, including Terramar Research, Angiology Research Foundation, and the Raymond and Beverly Sackler Foundation. Listed next door at 17 East 62nd Street was the Mortimer D. Sackler Foundation, the Sackler Lefcourt Center for Child Development, the Sackler Family Foundation, and the U.S. office for the Sackler School of Medicine in Tel Aviv. Although some of the companies had changed over time, 15 and 17 East 62nd Street were the same addresses highlighted by the Kefauver subcommittee investigators in 1960 as “components of the Sackler empire… cloaked in secrecy.”
II. Years later, Valium lost some of its notoriety when much more powerful street drugs made a resurgence. In 1993, River Phoenix, the twenty-three-year-old actor that Hollywood had dubbed “the next James Dean,” went into convulsions outside a West Hollywood nightclub. When his brother made a panicked call to 911, he said, “I’m thinking he had Valium.” He died at the hospital of a heroin and cocaine overdose.
III. Valium earned a dubious footnote in American history in March 1980 when a psychiatric outpatient tried assassinating Ronald Reagan. John Hinckley had been on a 15 mg daily dose of Valium. He took an additional 20 milligrams only hours before he shot Reagan. One of Hinckley’s lawyers charged that giving more Valium to Hinckley was like “throwing gasoline on a lighted fire.”
IV. Not even adding Xanax to Schedule IV of the Controlled Substances Act slowed its sales. In 1988 it was the world’s top selling pharmacological drug. It dominated the more than one hundred benzodiazepine drugs on the market in the 1990s.