The clinical use of clozapine and risperidone is reviewed. Traditional
antipsychotic drugs are effective for treating the positive symptoms
of schizophrenia but have little or no effect on the negative symptoms
of this disease. Newer antipsychotic agents, such as clozapine and ri
speridone, are effective for treating both positive and negative sympt
oms in acutely ill and treatment-resistant patients. Clozapine and ris
peridone also have a lower incidence of extrapyramidal symptoms (EPS)
than traditional antipsychotic drugs.Three hypotheses have been propos
ed to account for the newer agents' ability to relieve negative sympto
ms: (1) Improvement in negative symptoms may be linked to improvement
in positive symptoms. (2) Negative symptoms may improve in the absence
of the EPS often caused by traditional agents. (3) The newer antipsyc
hotic agents may directly affect the neural circuits that trigger nega
tive symptoms.