Clozapine is an antipsychotic medication that was first synthesized in 1956, but didn't reach clinical recognition for its ability to treat psychosis until the 1970s.
During that time, chlorpromazine had changed the way chronic psychosis was medically approached. Patients were now able to be treated for a condition that previously could only be offered custodial care. However, physicians were also finding that that 10-20% of patients did not respond to chlorpromazine or similar medications. These patients were referred to as treatment resistant.
In 1975 a brief letter was published in Lancet, a well-known medical journal. In the letter, the two key researchers reported that after clozapine was marketed in Switzerland, Austria, and West Germany, reports of agranulocytosis occurred. Agranulocytosis is a condition where patients have few or no neutrophils, a type of white blood cell that helps fight off infections. Patients with the condition can die due to overwhelming infection.
The 2 researchers reported "the occurrence of an alarmingly high number of cases in Finland within a short time" and their recommendation that patients receiving clozapine be carefully monitored. By 1977, further studies reviewed that the occurrence of agranulocytosis could be 20x higher within certain populations, and reported that likelihood could not be easily tracked using simple family pedigrees for genetic data.
Fast forward 50 years, and clozapine is now a widely used psychiatric medication for patients with treatment resistant psychosis However, patient monitoring has also co-evolved into a national system to help ensure that this potentially lethal medication can also be prescribed, dispensed, and monitored safely.
During the 20th century, nearly all current psychotropics were developed or refined. However, I consider clozapine a watershed innovation in psychiatry because it reminded a relatively new medical field that "medications for thoughts" can have systemic and serious effects that demand the careful practice of medicine.
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