Vol 2 n° 4 - Schizophrenia: General Findings
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Chlorpromazine, which was discovered in 1952, has an exhaustively characterized efficacy/safety profile compris- ing serious limitations: effectiveness in the field failing to match  efficacy  in  trials,  residual  symptoms  in  50%  of patients, a 20% relapse rate in compliant patients, and worrisome extrapyramidal side effects, including tardive dyskinesia in 5% per year. Second-generation “atypical” antipsychotics bypass these effects by having less affinity for the dopamine D2 receptor and affinities for other neu- roreceptors. Clozapine, the lead atypical antipsychotic, was followed in the mid 1990s by risperidone, olanzapine, and quetiapine,  which  now  account  for  over  half  of  new antipsychotic prescriptions in North America. The debate over their relative efficacy involves the potential well-being of millions of schizophrenics and billions of dollars. Atypi- cal antipsychotics are considerably more expensive; evi- dence for their superiority is highly variable and often inadequate, largely confined to short-term regulatory stud- ies. Their effects on long-term outcome (particularly neg- ative symptoms), relapse prevention, social and vocational functioning, suicide prevention and quality of life, and family and caregiver burden are largely unknown. The National Institute of Mental Health’s Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project is a com- bined efficacy–effectiveness trial that aims to answer these questions in a broad range of patients with schizophre- nia and Alzheimer’s disease. The modern era of treating psychotic disorders began in 1952 with the discovery that the compound chlorpromazine possessed antipsychotic properties and produced symptomatic improvement in patients with schizophrenia. Initially, chlorpromazine was termed a neuroleptic drug (derived from the Greek neuron and lepsis, meaning to “take hold of the nervous system”) to describe its effects of psychomotor immobilization.The implication was that the therapeutic antipsychotic prop- erties  and  adverse  motor  effects  were  inextricably linked.Thus, chlorpromazine and the numerous antipsy- chotic compounds that followed were initially consid- ered to belong to a class of neuroleptic drugs in which therapeutic    effects    were    inseparable    from    the extrapyramidal side effects (EPSs) they produced.1 Conventional antipsychotic drugs Conventional antipsychotic drugs or neuroleptics are known to be efficacious in treating psychotic symptoms. However, almost half a century of experience with con- ventional antipsychotic drugs has revealed their sub- stantial limitations. To varying degrees, all conventional antipsychotics carry the risk of side effects, including EPSs, hyperprolactinemia, and the neuroleptic malignant syndrome.2 The most worrisome form of EPS, tardive dyskinesia (TD), can be irreversible and its incidence has been estimated at about 5% a year.3 These medication Comparative effectiveness of antipsychotic drugs in schizophrenia T. Scott Stroup, MD, MPH; Jeffrey A. Lieberman, MD; Marvin S. Swartz, MD; Joseph P. McEvoy, MD Author affiliations: Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA (T. Scott Stroup, Jeffrey A. Lieber-man); Duke University School of Medicine, Durham, NC, USA (Marvin S. Swartz, Joseph P. McEvoy)

Keywords: antipsychotic drug; atypical antipsychotic drug; conventional antipsy-chotic drug; cost-effectiveness; schizophrenia; side effect

Address for correspondence: T. Scott Stroup, MD, MPH, Department of Psychiatry, C.B.# 7160, University of North Carolina, Chapel Hill, NC 27599-7160, USA
(e-mail: sstroup@css.unc.edu)

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