Founding Papers of Psychopharmacology: Cade on Lithium (1949), Delay, Deniker and Harl on Chlorpromazine (1952), Kuhn on Imipramine (1957)

Summary

This record brings together three short clinical papers that began the modern era of drug treatment in psychiatry. Before them, patients with severe mental illness were often confined for years in crowded hospitals, and the available physical treatments, such as sedation, insulin coma and electroconvulsive therapy, were limited or dangerous. In 'Lithium salts in the treatment of psychotic excitement', published in the Medical Journal of Australia in September 1949, John Cade described giving lithium to patients at a repatriation mental hospital near Melbourne. He had been searching for a toxic substance in the urine of manic patients and noticed that lithium made guinea pigs calm. Several of his ten patients with mania, some ill for years, improved strikingly and were able to leave hospital. Fears about lithium's toxicity delayed its acceptance until the Danish psychiatrist Mogens Schou and others tested it rigorously in the 1950s and 1960s. In 1952 Jean Delay, Pierre Deniker and J.-M. Harl of the Sainte-Anne Hospital in Paris reported in the Annales Médico-Psychologiques on the use of a new phenothiazine compound, numbered 4560 RP and later called chlorpromazine. The drug had been made by the Rhône-Poulenc company and used by the surgeon Henri Laborit to calm patients before operations. Given alone in steady doses, it quieted agitation and reduced hallucinations and delusions in psychotic patients without putting them to sleep. Within a few years chlorpromazine was used around the world, and hospital populations began to fall. In 1957 Roland Kuhn reported in the Schweizerische Medizinische Wochenschrift that an iminodibenzyl compound, G 22355, later named imipramine, relieved depression in many of his patients at Münsterlingen. The Geigy company had developed it as a possible treatment for psychosis; Kuhn, observing his patients closely, noticed its effect on depressed mood. Imipramine became the first tricyclic antidepressant. All three discoveries came from careful clinical observation rather than from theory, and each raised new questions about the brain and about the risks and limits of medication.

Top Lessons

• Observation in the clinic

  All three discoveries came from physicians watching their patients closely. Careful attention to individual patients remains essential in medicine.

• Benefits and risks

  Each drug brought great relief but also side effects and dangers. Medicine always weighs benefits against harms.

• Changing institutions

  The new drugs helped many patients leave hospitals, but closing institutions without adequate community care caused new problems.

• For the Christian reader

  The Gospels show Christ caring for those tormented in mind. Christians can welcome medicines that relieve such suffering while also attending to the whole person, body, mind and soul, and to the community that should surround the sick.

Verified Quotes

Medical Lens

The three clinical reports that introduced lithium, the first antipsychotic and the first tricyclic antidepressant.

• Cade (1949)

  Lithium salts used to calm mania.

• Delay, Deniker and Harl (1952)

  Chlorpromazine given for psychotic agitation.

• Kuhn (1957)

  Imipramine found to relieve depression.