The discovery of chlordiazepoxide and the clinical introduction of benzodiazepines: Half a century of anxiolytic drugs

The clinical introduction of chlordiazepoxide half a century ago was one of the major breakthroughs in the history of psychopharmacology, as it opened the door for the benzodiazepine saga, the pharmacological family par excellence in the treatment of anxiety disorders. This review analyses the discovery of this drug, which was filled with chance events, and numerous chemical and clinical errors of approach. Chlordiazepoxide, initially called methaminodiazepoxide, was patented in 1958 and introduced in clinical treatment in 1960 under the brand name Librium®. The benzodiazepines became the most widely prescribed drugs worldwide, provided truly effective treatment for “minor forms” (neuroses) of mental disorders for the first time, increased the quality of scientific methodology in clinical research, and enabled the development of new etiopathogenic theories for anxiety disorders, especially after the discovery in 1977 of their high-affinity receptor complex.

Research highlights
► The discovery of the benzodiazepines is closely linked to Leo Henryk Sternbach.
► Chlordiazepoxide consolidated the treatment of anxiety disorders.
► Thousands of benzodiazepines have been synthesised since 1960.
► Benzodiazepines were the most widely prescribed drugs in the world.
► The benzodiazepines’ discovery made considerable progress in neurosciences.