First- versus second-generation medications A major focus of research over the past decade has been to establish the relative merits of first- and second-generation antipsychotics. With that, psychiatry has seen the completion of several large, government-funded
trials, which attempted to apply some of the principles of effectiveness studies to complement data derived from more traditional efficacy Inhibitors,research,lifescience,medical research. Before providing an overview of these results and discussing their implications, it will be useful to set the stage for the shift in prescribing practices and the ensuing costeffectiveness questions that emerged in the 1990s. In the 1970s and 1980s, considerable effort went into solidifying our knowledge of the indications for and benefits and risks of long-term pharmacotherapy in schizophrenia. A large series of relapse-prevention studies were conducted demonstrating Inhibitors,research,lifescience,medical the ability of continuous antipsychotic drug administration to significantly reduce the risks of psychotic relapse and rehospitalization Inhibitors,research,lifescience,medical in comparison with placebo.1 Neurologic adverse effects At the same time, increasing
concern had developed regarding the potential of antipsychotic drugs to produce a variety of neurologic adverse effects, ranging from acute dystonic reactions to akathisia, parkinsonism, and tardive dyskinesia. Each one of these conditions were the subject of epidemiologic, treatment, and outcome studies which are beyond the scope of this review. Tardive dyskinesia became a particular concern because of its potential severity, persistence, and psychosocial as well as medicolegal consequences. A number of
prospective studies Inhibitors,research,lifescience,medical were conducted to determine the incidence Inhibitors,research,lifescience,medical and risk factors for tardive dyskinesia.2-4 In general, the risk of new cases of tardive dyskinesia was found to be 5% per year of cumulative drug exposure, with age and early occurring extrapyramidal side effects being two important risk factors. In elderly individuals (though with a different spectrum of diagnoses) receiving antipsychotic medications for the first time the incidence was generally fivefold higher.5 With the development of clozapine, the scientific and clinical community became convinced that it was possible to Tofacitinib concentration separate (-)-p-Bromotetramisole Oxalate the therapeutic effects of antipsychotic medications from their neurologic extrapyramidal effects. Although it took many years after these early observations before clozapine was used on a wide scale for treatment-refractory patients,6 the awareness of its lack of propensity to cause extrapyramidal effects provided considerable impetus in drug development and served as a model for “atypicality” (a concept which has outlived its usefulness, but did serve a useful heuristic function).