Covariance of Positive and Negative Symptoms during Treatment with Typical Neuroleptics and Clozapine

Although poor response to neuroleptics has traditionally been considered a characteristic feature of negative schizophrenic symptoms, several recent studies have documented significant improvement in negative symptoms in schizophrenic patients treated with neuroleptics. The question of whether neuroleptic-induced improvement in negative symptoms is linked to concomitant improvement in positive symptoms or occurs independently of such improvement is unresolved; it is also unclear if this profile is similar during treatment with clozapine and typical neuroleptics. To address these issues, we studied 120 RDC/DSM-III-R schizophrenic inpatients at drug-free baseline and after 3-4 weeks of treatment with clinically-determined doses of typical neuroleptics. We also studied 40 RDUDSM-III-R schizophrenic patients before a trial of clozapine and after 4-6 weeks of initiating clozapine treatment. Positive and negative symptoms were assessed by the BPRS “THOT” factor and the SANS sum of global scores, respectively. During treatment with typical neuroleptics, there was significant improvement in both positive symptoms (15.6k2.9 to 10.2k3.2) and negative symptoms (12.5k4.2 to 8.6k3.4); the change in positive symptoms was highly correlated to the change in negative symptoms (~0.60; p<O.OOl). During treatment with clozapine, both positive symptoms (from 16.of 3.6 to 12.4f3.5) and negative symptoms (from 13.8f4.5 to 10.5f4.1) improved significantly; change in positive symptoms was again significantly correlated to change in negative symptoms (1=0.63; p<O.Ol). Although there are sample differences between the two groups making comparisons difficult, these data indicate that negative symptoms improve along with positive symptoms in the course of initial neuroleptic treatment, both with typical neuroleptics and clozapine. Clozapine’s apparent greater efficacy on negative symptoms may bc related to its greater efficacy on positive symptoms (in otherwise treatment-refractory patients) and its lower propensity to cause EPS.