Annals of Clinical Psychiatry

The effectiveness of clozapine in the treatment of the negative symptoms of schizophrenia remains controversial, as improvements in negative symptoms are invariably accompanied by improvements in positive symptoms and neurological side effects. We examined the effectiveness of treatment with clozapine on negative symptoms in a cohort of patients with minimal positive symptoms. Improvements in positive and negative symptoms were measured by BPRS ratings in a subgroup of schizophrenic patients (n=17, from a state hospital cohort of 75) with minimal positive symptoms, who had received clozapine for 6 months. In this subgroup, significant improvements were noted by a composite score on the three negative symptom items of emotional withdrawal, blunted affect, and motor retardation. Positive and depressive symptoms remained unchanged. The remaining cohort (n=58) showed improvements in overall psychopathology including positive, negative, and depressive symptoms. Interestingly, nearly 50% of each group were discharged from the hospital. These findings suggest that clozapine may be beneficial in the treatment of core negative symptoms, even in the absence of other improvements in psychopathology. This effect of clozapine may be a function of its unique pharmacological profile.