Dr. Donald F. Klein, whose research into panic attacks, depression, childhood anxiety disorders, and related areas reshaped how such conditions are thought about and treated, died on Aug. 7 in Manhattan. He was 90.
His wife, Rachel Klein, said the cause was cardiopulmonary arrest.
In the 1950s, Dr. Klein, a psychiatrist with a background in biology, brought a new rigor to the study of whether some psychiatric problems might have a biological basis that could be treated with drugs. Psychotherapy was the go-to tool for treating depression and other problems at the time, and the use of medications was somewhat haphazard.
“Donald Klein began his research career at a time when psychiatry was struggling to find its footing in the broader scientific and medical community,” Dr. Daniel Pine, chief of the Section on Development and Affective Neuroscience at the National Institute of Mental Health, said by e-mail. “One of his most significant contributions was to extend approaches to psychiatry from other areas of medicine.”
Since psychiatric problems aren’t easily measured the way, for instance, a heart rate is, methods to gauge a medicine’s effects were needed. These included clinical observation, a patient’s own reports, and statistical analysis.
“Dr. Klein applied this approach to virtually all of the most impairing mental-health conditions of the last 50 years,” Pine said, “including problems with mood, anxiety, and psychosis.”
His work helped refine the definitions of certain psychiatric disorders and establish the legitimacy of treating them with drugs — a field known as psychopharmacology — along with traditional psychotherapy.
Dr. Harold Koplewicz, president of the Child Mind Institute, a nonprofit organization devoted to children with mental health disorders where Dr. Klein was the senior research adviser, put it simply:
“Don Klein was essentially the father of psychopharmacology.”
Donald Franklin Klein was born in New York City on Sept. 4, 1928. His father, Jesse, sold orthopedic shoes, and his mother, Rose (Bogachik) Klein, was a homemaker. He grew up in the Bronx and earned a bachelor’s degree at Colby College in Maine in 1947 at the age of 18.
Despite excellent grades, “I couldn’t get into medical school,” he said in an oral history recorded in 1994 for the American College of Neuropsychopharmacology, “probably because the vets had all come back then, but also anti-Semitism for medical school admission was very real.”
Instead he enrolled in the graduate program in biochemistry and physiology at New York University. After a year there he enrolled at the State University of New York School of Medicine, earning his M.D. in 1952.
He did an internship with the Public Health Service and then a first-year residency at the Creedmoor Psychiatric Center in Queens before returning to the Public Health Service for a stint at the Narcotic Hospital, a somewhat infamous institution in Lexington, Ky., for addicts — some of them prisoners, some there for treatment.
Working under Abraham Wikler, who was exploring the relationship between physiology, neurology, and addiction, Dr. Klein conducted several drug studies. After two years he returned to Creedmoor. In the late 1950s he joined Zucker Hillside Hospital in Queens, which was known for psychiatric research.
There, working under Max Fink, Dr. Klein became increasingly interested in psychopharmacology, collecting data on the effects of drugs on various conditions. He noticed that when patients with a particular type of panic disorder that included agoraphobia (fear of the open or crowded places) were given Thorazine, which was thought to be an anti-anxiety drug, they actually got worse. But when they were given Tofranil, an antidepressant, their panic attacks subsided.
“It struck everyone as very strange you would have an antidepressant drug knock out panic, the worst form of anxiety, and make it possible for patients who were afraid to leave a room to go out by themselves,” Dr. Klein said in the oral history.
He did additional studies and came away with a much more nuanced view of both depression and anxiety, as well as the notion that medicines could be used not only to treat but also to help figure out what was wrong to begin with.
“I came up with this idea of pharmacological dissection,” he said, “putting people together with a similar pattern of response to medication to see if there was something in their baseline state you could use diagnostically.”
That spirit of rigorous inquiry continued when Dr. Klein moved to Columbia University’s College of Physicians in 1976 and became director of research and chief of the Division of Therapeutics at the New York State Psychiatric Institute. He studied depression, panic disorder, the relation between childhood anxiety and problems in adulthood, and much more. And as a teacher, Koplewicz said, he was “an extraordinary mentor and trained generations of psychiatric investigators.”
Dr. Klein wrote or co-wrote several books, including “Understanding Depression: A Complete Guide to Its Diagnosis and Treatment,” with Dr. Paul Wender, another important figure in psychiatry. That book, published in 1993 and reissued in 2005, was aimed not only at physicians but also at patients and members of their families.
“A striking gap has grown between what is known by clinicians and researchers and what is known by the public,” they wrote.
“The public has been subjected to a bewildering flood of books explaining the origins of unhappiness — including depression — and other forms of human misery,” they added. “Most of these books have one thing in common: the positions they advance are not supported by scientific data.”
Dr. Klein’s first marriage, to Estelle Raben, ended in divorce. He married Rachel Kravetz, now a noted researcher in areas like attention-deficit hyperactivity disorder, in 1967. She survives him, along with five daughters, Dr. Beth Klein, Geri Armine-Klein, Dr. Hilary Klein, Dr. Erika Klein, and Michelle Gittelman; and eight grandchildren.
Pine said that Dr. Klein had stayed engaged with advancements and trends in the field even late in life. He was a proponent of the open science movement, which encourages the sharing of research and ideas, a philosophy he had long advocated in his teaching.
Once, Pine related, a student wanted to test a “particularly good idea” — the student’s words — and before telling Dr. Klein what it was, asked him to promise not to spread it around for fear that another student would steal it.
“So I want to make sure I understand,” Dr. Klein is said to have told the student. “You only want me to share your bad ideas?”