How effective are the second generation antipsychotics?

The past five years have witnessed a period of intense drug development for the treatment of schizophrenia. Second generation antipsychotics such as clozapine, risperidone, olanzapine, quetiapine and sertindole are now replacing the conventional antipsychotics in the treatment of schizophrenia at each point along its illness course. While there are few studies comparing these drugs, available evidence and clinical experience suggest that their different neuroreceptor affinity profiles translate into different benefits within specific clinical situations. Their relative efficacy in treatment- refractory schizophrenia and in the management of negative symptoms is of particular importance. While clozapine is currently the treatment of choice in treatment-refractory schizophrenia, there are some data to suggest that risperidone, olanzapine and sertindole are also effective in these patients, although higher doses may be required for the treatment of patients with severe schizophrenia. The benefit of second generation antipsychotics over conventional agents in the treatment of negative symptoms is more established. However, their relative efficacy on primary and secondary negative symptoms appears to differ. Thus, although the advantages of the second generation antipsychotics over conventional agents are acknowledged, there is a clear need for head-to-head comparisons to determine their relative efficacy in treatment-refractory schizophrenia and in the control of negative symptoms.