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Novel antipsychotics: issues and controversies. Typicality of atypical antipsychotics
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Abstract
En 中文
The typicality of atypical antipsychotic drugs remains debatable. Preclinical studies and findings from randomized, controlled and open trials of clozapine, olanzapine, risperidone, quetiapine, sertindole, ziprasidone and a substituted benzamide were examined. A MEDLINE search was conducted using key words, including extrapyramidal side effects, cognition, schizophrenia and the generic drug names. Over 140 articles from peer-reviewed journals were reviewed, some of which were based on a meta-analysis. New-generation neuroleptic agents were found to have greater efficacy on the negative symptoms of schizophrenia and to cause fewer unwanted extrapyramidal side effects (EPS) than the traditional antipsychotic drugs. On one hand, atypical neuroleptic agents could be strictly defined as any neuroleptic agent with antipsychotic effects at a dosage that does not cause extrapyramidal side effects. Thus, clozapine is regarded as the standard atypical antipsychotic drug. On the other hand, typicality is about dimension rather than category, and we suggest the use of the term spectrum of atypicality. For example, an emphasis is placed on quetiapine to illustrate where a new compound fits in this spectrum. Although dose-related, atypicality may be more a question of prescription attitude than of a specific characteristic of a compound. The degree to which a new compound is clinically superior to another atypical antipsychotic drug, in terms of improving positive, negative or affective symptoms, cognitive function and long-term outcome, will require further a priori hypotheses based on conceptual frameworks that are clinically meaningful. In addition, the results from industry-sponsored trials should be more comparable to those obtained from investigator-leading trials. Finally, the patient characteristics that define a patient's response to a specific antipsychotic drug are unknown.
Keywords:
antipsychotic agents
clozapine
cognition
receptors
dopamine
risperidone
schizophrenia
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