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Clozapine was synthesised in 1958, and first clinical trials were carried out in the 1960s. These trials already showed that the typical motor side-effects did not occur under clozapine treatment. Although the antipsychotic effect was recognised early, the manufacturer was reluctant to propose the introduction of clozapine as an antipsychotic agent, as it did not meet the “psychopharmacologic dogma” that antipsychotic effect could not be expected without extrapyramidal motor effect [1]. In 1972, clozapine was introduced in Austria, Switzerland, and Germany, within the following 5 years in 30 other countries. More than 100000 schizophrenic patients had been treated with clozapine, antipsychotic effect and tolerance were shown in 13 double-blind controlled studies [2among others]. The rapid increase in the distribution of clozapine dramatically stopped in 1974, when 16 patients developed agranulocytosis under clozapine treatment and eight of them died [3]. In many countries clozapine was withdrawn from the market, while in the German speaking countries, due to the intervention of several renowned psychiatrists, it was not withdrawn and since then is prescribed under precautionary restrictions. Pharmacological and clinical research on clozapine increased after Kane et al. [4] were able to prove the special effect of clozapine on treatment-resistant schizophrenics. That study led to the (re-)introduction of clozapine in most countries. |
