Conventional versus novel antipsychotics: changing concepts and clinical implications

Novel antipsychotics represent a significant advance in the treatment of sc hizophrenia after many years of few developments. The conventional antipsyc hotics are potent D-2 antagonists, but fail to achieve a response in about 30% of cases. They are also associated with a high rate of extrapyramidal s ide effects. The greater and broader spectrum of efficacy combined with the reduced short- and long-term side effects of the new drugs such as quetiap ine, risperidone, olanzapine and ziprasidone, contribute to a fresh optimis m for the pharmacotherapy of schizophrenia. These novel agents are now driv ing further advances in schizophrenia research through a growing understand ing of their pharmacological and clinical profiles. Clozapine, the first no vel antipsychotic, has relatively low activity at D-2 receptors, a high aff inity for D-4 receptors and a greater 5-HT2 (serotonin) than D-2 antagonism . Hence, clozapine and other novel antipsychotics can be classified as such by this latter characteristic. However, some of these drugs have D-2 occup ancy greater than 60% (the clinical response threshold), while others have a lower D-2 occupancy. The novel antipsychotics according have also been cl assified according to their activity on different neurotransmitter systems. While more effective, novel antipsychotics are not a panacea; they have li mitations and side effects. In clinical practice, the American Psychiatric Association recommends either a conventional or novel antipsychotic for ini tial treatment of schizophrenia, whereas Canadian guidelines recommend nave l agents. These agents should also be considered for treatment of refractor y schizophrenia. Patients whose schizophrenia does not respond to one of th ese agents may respond to another. Future research should involve longer cl inical trials, given the long periods needed to establish efficacy, and sho uld address many remaining questions about the novel agents.