Clozapine treatment for negative signs and cognitive impairment in schizophrenia

Early studies of the effect of clozapine on negative symptoms from the early 70‘s till mid 90‘s pointed an efficacy of the treatment on negative symptoms. These findings established clozapine as the only pharmacotherapy available for those patients. However, in recent more detailed studies clozapine had found to have limited or no added value to other antipsychotics. In contrast, clozapine effect on cognition seems to have mixed results. Recent evidence suggests that clozapine metabolites might have a role, specifically N-desmethylclozapine (NDMC). Treatment with clozapine potential for positive impact on cognition might be linked to the NDMC level rather than to the clozapine’s. In this chapter, we will describe the evidence for the effect of clozapine on negative symptoms and cognitive impairment in schizophrenia.