The history of clozapine and its emergence in the US market: A review and analysis

Department of Psychiatry, University of Rochester, School of Medicine and Dentistry, 300 Crittenden Blvd, Rochester, NY 14642, USA.
History of Psychiatry (Impact Factor: 0.26). 04/2007; 18(1):39-60. DOI: 10.1177/0957154X07070335
Source: PubMed


Clozapine is known as the first 'atypical' medication and is effective in people who have treatment-resistant schizophrenia. Its 1990 emergence in the USA was marked by considerable controversy over its high cost, due in large part to having been both the first new antipsychotic medication to come to market in over a decade and the need for comprehensive safety monitoring within a decentralized health system. This paper traces the history of clozapine's discovery and development in Europe, its part in the 1975 Finnish agranulocytosis scare, and its subsequent volatile emergence in the USA. Analyses examine peripheral forces at the time, particularly the influence of political, corporate, medical and societal forces which shaped its market course.

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    • "Clozapine was first introduced in Europe in 1971, and was approved by the FDA to treat refractory schizophrenia in 1989.52 It acts as a 5-HT2A, 5-HT2C, and 5-HT3 antagonist and, to a lesser extent, as a D1 antagonist.9 "
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    • "The era of " atypical " or " second generation " antipsychotic medications is a long and circuitous one dating back to the late 1950s (Crilly 2007; Hippius 1999), but systematic study of the effects of second generation antipsychotic medications on the neuropsychological deficits in schizophrenia began in the early to mid-1990s. The subsequent decade brought some suggestions that second generation antipsychotic medications might partially improve certain aspects of neurocognitive functioning (Harvey and Keefe 2001; Keefe et al. 1999; Meltzer and McGurk 1999; Woodward et al. 2005). "
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    • "Antipsychotic medications were developed to treat schizophrenia and related conditions (e.g., schizotypal and delusional disorders) (Crilly, 2007), and their use is label trial showed that olanzapine was effective as an antiemetic and well tolerated by cancer patients (15 out of 16 patients completed the protocol with 87% of them having no vomiting episodes) (Passik et al., 2004). These findings were further confirmed as the use of olanzapine was tested at maximum tolerated dose (no vomiting episodes in 8 out of 10 patients receiving highly emetogenic chemotherapy and in 17 out of 20 patients receiving moderately emetogenic chemotherapy) (Navari et al., 2005) as well as in combination with other agents (no vomiting episodes in 6 out of 8 patients receiving highly emetogenic chemotherapy and in 23 out of 32 patients receiving moderately emetogenic chemotherapy) (Navari et al., 2007). "

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