1952: Chlorpromazine and the Psychopharmacology Revolution (1952)

Before 1952, the treatment of schizophrenia and other psychoses was limited to physical restraint,
hydrotherapy, insulin coma therapy, and lobotomy. Psychiatric hospitals were custodial institutions
housing hundreds of thousands of patients with no expectation of improvement or discharge.

Chlorpromazine's discovery emerged from work on antihistamines. French chemist Paul Charpentier at
Rhône-Poulenc synthesised chlorpromazine in 1950 as a compound to potentiate anaesthesia. Surgeon
Henri Laborit noted its profound calming effect in surgical patients and encouraged psychiatrists
to try it in psychotic patients. On 19 January 1952, psychiatrists Jean Delay and Pierre Deniker
at the Sainte-Anne Hospital in Paris administered chlorpromazine to their first schizophrenic
patient, a severely agitated 24-year-old man who responded dramatically after three weeks of
treatment. Their 1952 publications established chlorpromazine as the first antipsychotic drug.

The drug reached the US market in 1954 as Thorazine and was almost immediately adopted by
state psychiatric hospitals. The US psychiatric hospital population, which had peaked at over
550,000 in 1955, began declining sharply—primarily attributable to chlorpromazine. This
deinstitutionalisation, though imperfectly executed, transformed psychiatry's entire model
of care.

Chlorpromazine's mechanism—dopamine D2 receptor blockade—was identified in the 1970s by Arvid
Carlsson and others. This finding established the dopamine hypothesis of schizophrenia, guided
the development of all subsequent antipsychotics, and contributed to Carlsson's 2000 Nobel Prize
in Physiology or Medicine.