Clozapine is an atypical antipsychotic agent with a unique therapeutic profile: in contrast to conventional neuroleptics, clozapine is more effective in decreasing positive and negative symptoms in treatment-refractory schizophrenic patients and causes fewer extrapyramidal side-effects (EPS) and tardive dyskinesia. It has been found to produce greater improvement in negative symptoms than typical neuroleptics. Meltzer (1990, 1991) observed that negative symptoms improved independently of change in positive symptoms in schizophrenic patients treated with clozapine; he noted that clozapine differed from conventional neuroleptics in this regard. The question of whether the observed greater efficacy of clozapine in treating negative symptoms is related to its greater efficacy in treating positive symptoms in this population of schizophrenic patients or whether the clozapine-associated reduction in negative symptoms occurs independently of such improvement has obvious pathophysiological
and clinical importance. To study this question, we assessed positive and negative symptoms in a sample of 40 schizophrenic patients before and about 8 weeks after
an open clinical trial of clozapine.
Results Both positive and negative symptoms improved significantly (p < .01) with clozapine treatment (Table 1). Use of the BPRS “ANER” factor (emotional withdrawal, motor retardation, and blunted affect) instead of the SANS sum of global scores to define negative symptoms did not alter the findings. Change in negative symptoms was significantly correlated to change in positive symptoms (Fig. 1).
Change in negative symptoms was significantly correlated to change in positive symptoms
These data indicate that clozapine is similar to typical neuroleptics with regard to improvement in negative symptoms and their covariance with positive symptoms. In com-parison to typical neuroleptics, the apparent greater efficacy of clozapine in treating negative symptoms may be related to its greater efficacy in treating positive symptoms in treatment-refractory patients and its lower propensity to cause EPS.