ABSTRACT
This chapter will build on the foundation established in the previous chapter, where we reviewed the discovery of chlorpromazine and the many first-generation antipsychotics that followed, all of which were marked by varying degrees of neurological and physiological side effects secondary to their blockade of multiple cell receptors. We noted the shift to high-potency first-generation agents and the ongoing concerns about neurological side effects and the lack of any significant advances in efficacy, despite the remarkable increase in costs. We then reviewed the discovery of clozapine, the first second-generation antipsychotic; the debate over its efficacy in treatment-resistant schizophrenia; its approval for treatment of suicidality; its affinity for serotonin receptors; and its lack of neurological side effects, all of which led to the rapid development of olanzapine, risperidone, and other second-generation drugs. In this chapter, we will examine the seemingly paradoxical increase in the mortality and morbidity of psychiatric disorders and, in some instances, a fall-off in outcome. We shall also examine the data showing few differences in outcome when the older drugs are compared with second-generation agents, despite the very high initial costs.
