Background/objective: Schizophrenia is a chronic and disabling psychiatric disorder that requires lifelong medication. The past 15 years led to the introduction of a number of new drugs ('atypical') that have dramatically displaced the older drugs ('typical'), at least in Western markets. As the dust settles on this period and substantial data, as well as practical prescribing experience, are available, we examine what has been gained and what can be learned.
Methods: Information available from various medical database resources: MEDLINE, EMBASE, Cochrane Database, ClinicalTrials.gov (a registry of federally and privately supported clinical trials) and schizophreniaforum.org--Drugs in Clinical Trials for Schizophrenia.
Results/conclusion: It seems that the clinical benefits of the newer second-generation antipsychotics are modest, the greatest advantage being a reduction in motor side effects. The earlier hope that these agents have a primary effect on negative and cognitive symptoms is harder to sustain. Clozapine remains superior, even to other atypical antipsychotics, in treating refractory schizophrenia. On a mechanistic level, it seems that dopamine D(2) blockade is necessary and even sufficient for antipsychotic response (at least in some), though other receptors may contribute in ways that are not yet well understood.