The Evolution of Clozapine in Schizophrenia Treatment

What is clozapine?

Not only is clozapine the gold standard medication for treatment-resistant schizophrenia, it is also one of the most unique drugs used in psychiatry.

It was synthesized 1958, only eight years after chlorpromazine, the first antipsychotic drug, was created. At that time, researchers tested for antipsychotic properties by taking various compounds and testing to see if lab mice developed dystonia and catalepsy. When researchers tested clozapine, they found that it did not cause dystonia, but instead made the mice sleepy. Because of this, clozapine was almost missed entirely as an antipsychotic medication. Eventually, however, clozapine was found to be more successful than other antipsychotic drugs.

By the 1970s, Austria, Germany, and Finland had produced positive data on clozapine proving its efficacy. However, clozapine was also found to have caused severe neutropenia in sixteen patients in Finland, and even caused the death of eight of those patients. For this reason, clozapine did not enter the United States until it was approved by the FDA in 1989.

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