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.
"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 "
[Show abstract][Hide abstract] ABSTRACT: Tourette syndrome (TS) is a neuropsychiatric disorder with typical onset in childhood and characterized by chronic occurrence of motor and vocal tics. The disorder can lead to serious impairments of both quality of life and psychosocial functioning, particularly for those individuals displaying complex tics. In such patients, drug treatment is recommended. The pathophysiology of TS is thought to involve a dysfunction of basal ganglia-related circuits and hyperactive dopaminergic innervations. Congruently, dopamine receptor antagonism of neuroleptics appears to be the most efficacious approach for pharmacological intervention. To assess the efficacy of the different neuroleptics available, a systematic, keyword-related search in PubMed (National Library of Medicine, Washington, DC) was undertaken. Much information on the use of antipsychotics in the treatment of TS is based on older data. Our objective was to give an update and therefore we focused on papers published in the last decade (between 2001 and 2011). Accordingly, the present review aims to summarize the current and evidence-based knowledge on the risk-benefit ratio of both first and second generation neuroleptics in TS.
"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). "
[Show abstract][Hide abstract] ABSTRACT: Application of a neuropsychological perspective to the study of schizophrenia has established a number of important facts about this disorder. Some of the key findings from the existing literature are that, while neurocognitive impairment is present in most, if not all, persons with schizophrenia, there is both substantial interpatient heterogeneity and remarkable within-patient stability of cognitive function over the long-term course of the illness. Such findings have contributed to the firm establishment of neurobiologic models of schizophrenia, and thereby help to reduce the social stigma that was sometimes associated with purely psychogenic models popular during parts of the 20th century. Neuropsychological studies in recent decades have established the primacy of cognitive functions over psychopathologic symptoms as determinants of functional capacity and independence in everyday functioning. Although the cognitive benefits of both conventional and even second generation antipsychotic medications appear marginal at best, recognition of the primacy of cognitive deficits as determinants of functional disability in schizophrenia has catalyzed recent efforts to develop targeted treatments for the cognitive deficits of this disorder. Despite these accomplishments, however, some issues remain to be resolved. Efforts to firmly establish the specific neurocognitive/neuropathologic systems responsible for schizophrenia remain elusive, as do efforts to definitively demonstrate the specific cognitive deficits underlying specific forms of functional impairment. Further progress may be fostered by recent initiatives to integrate neuropsychological studies with experimental neuroscience, perhaps leading to measures of deficits in cognitive processes more clearly associated with specific, identifiable brain systems.
"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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