When researchers began tinkering with a class of tranquilizer drugs called benzodiazepines in the 1950s, they felt they had uncovered a solution to modern anxiety and insomnia. Benzodiazepines worked quickly and effectively to quell racing heartbeats and dismiss spinning thoughts. The dozen or so different types — including Xanax, Valium, Ativan and Klonopin — became the most frequently prescribed drugs around the world, even as concerns arose about their potential side effects and addictive properties.
“Patients themselves, and not the medical profession, were the first to realize that long-term use of benzodiazepines can cause problems,” wrote Dr. Heather Ashton, a British psychopharmacologist.
She said that patients who had been on the medications for months or years would come to her with fears that the drugs were making them more ill. Some continued to have symptoms of depression or anxiety. Others had developed muscle weakness, memory lapses, or heart or digestive issues.
Ashton would dedicate much of her career to listening to hundreds of patients’ experiences and rigorously collecting data.
The result of her work, in 1999, was “Benzodiazepines: How They Work And How To Withdraw.”
Now known simply as “The Ashton Manual,” it has become a cornerstone for those looking to quit the drugs safely. Addiction researchers worldwide still cite it in studies on benzodiazepines. And patient support groups have translated and distributed it in about a dozen languages.
Ashton died on Sept. 15, 2019, at her home in Newcastle upon Tyne, England. She was 90.
Her death, which had not been widely reported, was confirmed by her son John.
“Heather was a remarkable person,” Nicol Ferrier, an emeritus professor of psychiatry at Newcastle University who worked closely with Ashton, said in an interview. “She was very upset by this problem of benzodiazepine dependence that was essentially caused by doctors overprescribing the medications, and she took it upon herself to help patients struggling to withdraw from them.”
From 1982 to 1994, Ashton ran a benzodiazepine withdrawal clinic at the Royal Victoria Infirmary in Newcastle, tailoring her tapering schedules for each patient. She acknowledged that benzodiazepines could be useful in the short term, but said that they should not be taken for longer than two to four weeks. Long-term use, she found, often led to physical dependence. The brain adapted to the sedative effect of the drugs to the point where patients would pop a calming pill just to treat the symptoms of withdrawal since the previous dose. Patients who tried to quit cold turkey faced extreme restlessness, irritability, insomnia, muscle tension, racing heartbeats and other debilitating symptoms.
Ashton concluded that people needed to slowly reduce the dose of their medication, sometimes over the course of six months or more. She explained this strategy in her manual, using examples from patients she had treated herself.
“Her work both honored her patients and turned out to be more helpful than any randomized, controlled trial,” said Dr. Anna Lembke, an associate professor of psychiatry and behavioral sciences at Stanford University, where she leads the school’s Stanford Addiction Medicine Dual Diagnosis Clinic.
Ashton’s work was also timely. Scientists were starting to realize that patients who became dependent on benzodiazepines often misused opioids as well. One study found that the overdose death rate among patients taking both benzodiazepines and opioids was 10 times higher than among those who only took opioids.
But unlike opioid prescriptions, which started declining after 2012, benzodiazepine prescriptions continued to rise. Doctors still had limited awareness of benzodiazepines’ addictive potential and some patients could continue on the same steady dose for years without exhibiting any symptoms or obvious changes in behavior.
“If patients take them only as prescribed by their doctor, then they don’t meet criteria for addiction, because addiction involves behaviors that correspond to compulsive drug-seeking,” Lembke said. “But really, if you look at what’s happening in the brain, it’s probably not that different.”
In 2013, the British National Formulary, which advises doctors on prescribing practices, updated its guidelines to recommend benzodiazepines for short-term use only and to suggest a withdrawal schedule based on Ashton’s manual. In 2018, it revised its recommendations again to suggest an even slower withdrawal, based on evidence that Ashton and other researchers had collected.
The United States followed suit, with the Food and Drug Administration requiring that all benzodiazepines carry a so-called black-box warning about the drugs’ side effects, and that doctors check their state’s prescription drug monitoring program to see whether a patient had been given any federally controlled and addictive medications in the past 12 months.
“Basically, we now recommend using the same kind of interventions that are used to address the opioid crisis to address the benzodiazepine overprescribing crisis,” Lembke said. “Dr. Ashton was the vanguard of that change.”
Chrystal Heather Champion was born on July 11, 1929, in Dehradun, India, to Harry Champion, a forester, and Chrystal (Parsons) Champion. Her parents sent her to boarding school in England when she was 6, but in 1939, during World War II, she and her older brother, Jim, were among millions of children evacuated from Britain to live with relatives and foster families overseas.
The two ended up in the care of John and Obi Marshall in West Chester, Pennsylvania. They became a second family, and Heather remained in close touch with the Marshalls for the rest of her life.
She returned to England in 1945 and went on to study medicine at the University of Oxford. After graduating, she married John Ashton and moved to London, where he worked as an economist for the Ministry of Agriculture. They moved to Newcastle in 1964, when John was appointed a professor of agricultural economics at Newcastle University. Heather Ashton was hired by the university’s department of pharmacological sciences, where she developed her expertise in psychoactive drugs.
In addition to benzodiazepines, she conducted several studies on the effects of nicotine and cannabis in the brain, and was among the earliest researchers to use electroencephalography to understand changes in neural activity.
She took great pains to avoid any conflict of interest that might undermine people’s trust in her work or profession. She scrupulously declined support of any kind from the pharmaceutical industry.
Even after she retired, Ashton continued publishing original research, seeing patients and teaching medical students. She also remained active on the executive committee of the North East Council on Addiction and would answer requests for advice on benzodiazepine dependence that poured in from around the world.
As she aged, she relied on her son John to help her type responses to emails.
“She always put the interests of patients before everything else,” he said.
In addition to John, she is survived by two other sons, Jim and Andrew; a daughter, Caroline Ostler; and six grandchildren. Her husband died in 1986.