Following the introduction of the first neuroleptics in the 1950s, pharmaceutical companies continued screening compounds for psychoactive properties. In 1959, at Wander Laboratories (ultimately purchased by Sandoz), researchers were surprised to discover a chemical similar to tricyclic antidepressants that had antipsychotic properties. They named it clozapine. But the drug initially received little attention. It was called a “defective” or “atypical” molecule by the people developing theories about what properties made a neuroleptic work, and neuroleptic dogma held that a compound could only be effective as an antipsychotic if it produced extrapyramidal symptoms (EPS). Besides all that, the early studies were published in German, and not too many people read them. But in the early 1970s, Stille and Hippius produced data showing that clozapine worked, and it was released in Europe, only to be recalled after a 1974 study in Finland raised the specter of agranulocytosis. We know what became of the drug, but what about its moniker? The term “atypical” has come to represent different things to different people: drugs that don’t produce EPS, drugs that improve negative as well as positive symptoms, drugs that cost the health care system large amounts of money. It may be time for a change, but it’s a sticky term; we at TCR tried last year to switch to “second-generation antipsychotics,” but somehow the old term keeps creeping back.

Source: J Clin Psychiatry 1999; 60[suppl 12]:22-23