PubMed · 12668398
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Karen P Hayhurst, Petra Brown, Shon W Lewis. 2003. Postcode prescribing for schizophrenia.. https://doi.org/10.1192/bjp.182.4.281
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Common adverse effect measures in psychiatric trials are typically analysed with repeated measures ANOVA, despite having distributions which violate key assumptions of that method; moreover, some adverse effects may be concentrated in vulnerable subgroups of participants. For testing treatment differences in adverse effects, we propose use of Kendall's taub as a summary measure of within-participant trends in adverse events, in conjunction with a weighted modification of a rank test proposed by Conover and Salsburg. Data on extrapyramidal side effects from a controlled clinical trial conducted in persons with treatment resistant schizophrenia was used to compare the proposed analysis to repeated measures ANOVA using mixed models and alternate tests for treatment differences in taub trend scores.
With the introduction of atypical neuroleptics, the therapy of schizophrenia has been improved by a group of antipsychotic substances characterized by better tolerability concerning extrapyramidal side effects and higher efficiency against negative symptoms. However, these atypical antipsychotics are not a homogeneous class of drugs but rather represent a group of substances with very different neurobiologic, pharmacologic, and clinical features. This fact and the growing variety of available atypical neuroleptics illustrate the difficulty in choosing the "right" antipsychotic drug for each patient. The aim of this investigation was to evaluate preliminary empirical data for possible differential indication of atypical neuroleptics by a questionnaire-based survey of 192 physicians in ten psychiatric hospitals active in the biological psychiatry work group of the German Federal Directors' Conference.
The treatment of schizophrenia has evolved over the past half century primarily in the context of antipsychotic drug development. Although there has been significant progress resulting in the availability and use of numerous medications, these reflect three basic classes of medications (conventional (typical), atypical and dopamine partial agonist antipsychotics) all of which, despite working by varying mechanisms of actions, act principally on dopamine systems. Many of the second-generation (atypical and dopamine partial agonist) antipsychotics are believed to offer advantages over first-generation agents in the treatment for schizophrenia. However, the pharmacological properties that confer the different therapeutic effects of the new generation of antipsychotic drugs have remained elusive, and certain side effects can still impact patient health and quality of life. Moreover, the efficacy of antipsychotic drugs is limited prompting the clinical use of adjunctive pharmacy to augment the effects of treatment. In addition, the search for novel and nondopaminergic antipsychotic drugs has not been successful to date, though numerous development strategies continue to be pursued, guided by various pathophysiologic hypotheses. This article provides a brief review and critique of the current therapeutic armamentarium for treating schizophrenia and drug development strategies and theories of mechanisms of action of antipsychotics, and focuses on novel targets for therapeutic agents for future drug development.