Klein, Donald F.

   (1928–)

   One of the pioneers of psychopharmacology and nosology in the United States in the 1960s and after, Klein was born in New York City. He trained at Creedmoor State Hospital and served from 1953 to 1958 at the U.S. Public Health Service Narcotics Hospital in Lexington, Kentucky. From 1959 to 1976, he was a research psychiatrist at Hillside Hospital in Glen Oaks, New York, in the department of experimental psychiatry that Max Fink had founded in 1956, advancing to director of research and evaluation. In 1974, Hillside Hospital merged and became the Long Island Jewish-Hillside Medical Center. In 1976, he became professor of psychiatry at Columbia University medical school and director of research at New York State Psychiatric Institute. Although a candidate at the New York Psychoanalytic Institute between 1957 and 1961, Klein’s interest, as he put it, "turned to other, more promising, directions."

   In 1962, Klein and Fink at Hillside found in a placebo-controlled randomized trial that depressed patients benefited from chlorpromazine, a phenothiazine-class antipsychotic medication, just as well as patients treated with imipramine, the first tricyclic antidepressant. This finding, published in the Archives of General Psychiatry, further challenged* the distinction then forming between "antipsychotics" and "antidepressants." Two years later, in an article in Psychopharmacologia in 1964, Klein suggested on the basis of a double-blind placebo-controlled trial that "anxiety" was not a single affect. Spontaeous panic and anticipatory anxiety could be distinguished on the basis of response to medication. Hospitalized agoraphobic patients had their spontaneous panic attacks remit during imipramine treatment but maintained high levels of anticipatory anxiety and phobic avoidance. Furthermore, these patients did poorly on chlorpromazine, which was then considered a powerful agent in psychotic anxiety, as psychosis was then considered due to extreme anxiety.

   The article marked the beginning of the emergence of panic disorder as an independent disease entity. Moreover, it opened a new chapter in psychopharmacology with "the use of patterns of drug response as dissecting tools" in delineating diseases. One of the earliest textbooks in the uses of psychotropic drugs, Diagnosis and Drug Treatment of Psychiatric Disorders (1969), was co-authored by Klein with John M. Davis (1933–), who was then a psychopharmacologist at the National Institute of Mental Health.

   In 1974, Klein proposed in the Archives of General Psychiatry "endogenomorphic depression," a diagnosis that cut across the reactive vs. endogenous distinction, as a revision to the depression nosology. Although the diagnosis was not taken up in DSM-III, the core criteria of loss of interest and pleasure were accepted. It also led to research in "atypical depression." (See Depression: Recent Concepts: atypical depression (revived) [1979].) At the New York State Psychiatric Institute, which is linked to the department of psychiatry of Columbia University, Klein was the senior figure in a group of researchers including Frederic Quitkin (1937–) and Michael Liebowitz (1945–). They devised innovative ways of looking at depressive and anxiety disorders, including "social anxiety disorder." They also called attention to the benefits of the then neglected monoamine oxidase inhibitor class of antidepressant drugs. (See Iproniazid.)