Surprising origin of antipsychotic drugs | Andrew Scull and Lex Fridman
Andrew Scull explains how chlorpromazine, an antihistamine synthesized in the 1880s, was accidentally discovered to have psychiatric applications in the 1950s through French Navy lieutenant Alain Laborit's experiments. The drug's rapid adoption was driven by pharmaceutical companies' aggressive marketing to politicians and hospital administrators rather than by psychiatrists' initial enthusiasm, transforming it from a 'major tranquilizer' into the first 'antipsychotic' drug.
Summary
The discussion traces the surprising origin of antipsychotic drugs to the post-World War II era when pharmaceutical companies, enriched by antibiotic discoveries like penicillin, began investigating new drug applications. French company Rhône-Poulenc possessed chlorpromazine, an antihistamine originally synthesized in 1880s Germany, but had no clear market for it. In an era with no regulatory controls on drug testing, the company distributed the compound to various doctors to explore potential uses—from treating car sickness and eczema to serving as an anesthetic potentiator.
The pivotal moment came when French Navy lieutenant Alain Laborit tested chlorpromazine as an anesthetic potentiator and noticed it made presurgical patients stop being anxious. He wrote to relatives working in Paris mental hospitals comparing the effect to a 'chemical lobotomy.' This led psychiatrists Delay and Deniker at Sainte-Anne's hospital in Paris to test it on psychiatric patients. By increasing dosages, they found that agitated patients became calmer, stopped violent behavior, and became less mobile while maintaining consciousness. The drug was initially marketed as a 'major tranquilizer' due to its sedating effect, and hospitals saw it primarily as a behavioral control tool.
The drug's adoption in North America came through Quebec psychiatrist Hans Lehmann, who conducted early uncontrolled trials on 15 patients. When Rhône-Poulenc sought to sell the rights to American companies, the first two pharmaceutical firms rejected it, but Smith Kline & French recognized its commercial potential. The company employed sophisticated marketing strategies, targeting state legislators with moving pictures showing agitated patients becoming calm, effectively creating what would become known as 'big pharma' marketing. Within two years of FDA approval in 1954, two million Americans were taking the drug.
Scull notes that the drug's success sparked the emergence of 'minor tranquilizers' like Miltown (promoted by television star Milton Berle as 'Uncle Miltown') in 1955, followed by Valium and Librium in the 1960s. Notably, Freudian psychiatrists resisted these drugs, but hospital psychiatrists embraced them. In the early 1960s, the terminology shifted from 'major tranquilizers' to 'antipsychotics,' suggesting the drugs attacked underlying psychosis rather than merely controlling behavior. Scull clarifies that antipsychotics effectively reduce positive symptoms (hallucinations, delusions, and agitation) in many patients but have little effect on negative symptoms (apathy, social withdrawal, poverty of language, lack of initiative), which remain equally devastating.
About this episode
Lex Fridman Podcast full episode: https://www.youtube.com/watch?v=s7d2d8FhevU Thank you for listening ❤ Check out our sponsors: https://lexfridman.com/sponsors/cv10064-sb See below for guest bio, transcript, links, and to give feedback, submit questions, contact Lex, etc. *GUEST BIO:* Andrew Scull is a historian of psychiatry. *Transcript:* https://lexfridman.com/andrew-scull-transcript *CONTACT LEX:* *Feedback* - give feedback to Lex: https://lexfridman.com/survey *AMA* - submit questions, videos or call-in: https://lexfridman.com/ama *Hiring* - join our team: https://lexfridman.com/hiring *Other* - other ways to get in touch: https://lexfridman.com/contact *EPISODE LINKS:* Andrew's Website (UCSD faculty page): https://sociology.ucsd.edu/people/faculty/emeritus/andrew-scull.html Desperate Remedies (book): https://amzn.to/4vmBquI Madness in Civilization (book): https://amzn.to/3SZhd0I *SPONSORS:* To support this podcast, check out our sponsors & get discounts: *Wispr Flow:* AI-powered voice dictation app. Go to https://lexfridman.com/s/wispr_flow-cv10064-sb *Fin:* AI agent for customer service. Go to https://lexfridman.com/s/fin-cv10064-sb *LMNT:* Zero-sugar electrolyte drink mix. Go to https://lexfridman.com/s/lmnt-cv10064-sb *Shopify:* Sell stuff online. Go to https://lexfridman.com/s/shopify-cv10064-sb *BetterHelp:* Online therapy and counseling. Go to https://lexfridman.com/s/betterhelp-cv10064-sb *Perplexity:* AI-powered answer engine. Go to https://lexfridman.com/s/perplexity-cv10064-sb *PODCAST LINKS:* - Podcast Website: https://lexfridman.com/podcast - Apple Podcasts: https://apple.co/2lwqZIr - Spotify: https://spoti.fi/2nEwCF8 - RSS: https://lexfridman.com/feed/podcast/ - Podcast Playlist: https://www.youtube.com/playlist?list=PLrAXtmErZgOdP_8GztsuKi9nrraNbKKp4 - Clips Channel: https://www.youtube.com/lexclips *SOCIAL LINKS:* - X: https://x.com/lexfridman - Instagram: https://instagram.com/lexfridman - TikTok: https://tiktok.com/@lexfridman - LinkedIn: https://linkedin.com/in/lexfridman - Facebook: https://facebook.com/lexfridman - Patreon: https://patreon.com/lexfridman - Telegram: https://t.me/lexfridman - Reddit: https://reddit.com/r/lexfridman
Key Insights
- Chlorpromazine was an 1880s antihistamine with no known market application that was distributed to doctors in an uncontrolled fashion to find any possible therapeutic use, including treatments for car sickness, eczema, and as an anesthetic enhancer.
- Alain Laborit discovered the psychiatric potential of chlorpromazine by accident when testing it as an anesthetic potentiator and observing that presurgical patients stopped experiencing anxiety, leading him to describe it as a 'chemical lobotomy.'
- Pharmaceutical companies, not psychiatrists, drove the adoption and marketing of antipsychotics by targeting politicians and state legislatures with compelling visual demonstrations of the drug's calming effects on agitated patients.
- Smith Kline & French rejected by two larger pharmaceutical companies, acquired chlorpromazine rights and transformed from a small operator into a major pharmaceutical company, with two million Americans taking the drug within two years of 1954 FDA approval.
- Antipsychotics effectively reduce positive symptoms of schizophrenia (hallucinations, delusions, agitation) but have little to no effect on negative symptoms (apathy, social withdrawal, poverty of language, lack of initiative), which are equally devastating to patients.
Topics
Transcript
[0:02] The war I think greatly accelerates again World War II greatly accelerates things not least because we discover a real magic bullet called penicillin and then the other antibiotics that we subsequently come across. Penicillin had been observed by Alexander Fleming in his famously in his lab in some tube petri dishes where bacteria had been killed. Later was one of the co-winners of a Nobel Prize and made a lot of capital out of that discovery. It was [0:36] really Harold Florey and his team at Oxford who developed the therapeutic potential of penicillin and actually Florey flew some of it in his jacket across the Atlantic to America and it was Americans that solved the critical thing.…
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