Abstract
It has been established that clozapine is more effective in decreasing both the negative and positive symptoms of schizophrenia than standard antipsychotics. In addition to having positive and negative symptoms, however, persons with schizophrenia have multiple deficits on neuropsychological exams. Some of these deficits have been shown to be mediated by functioning in the dorsolateral prefrontal cortex, and have been found to be correlated with prominent symptoms of schizophrenia such as conceptual disorganization and the deficit syndrome. These prefrontal deficits seriously impair the learning of new material, ability to problem-solve, and attentional functioning. Whether clozapine ameliorates these underlying deficits is not known as the literature in this area presents a mixed picture. The current study tested the hypothesis that some neuropsychological measures known to be impaired in schizophrenic patients both on and off standard medication would improve with clozapine treatment. The Neurological Exam Scale (NES) is a 26-item test covering three functional areas: integrative sensory dysfunction, motor incoordination, and impaired sequencing of complex motor acts. The NES was administered to 8 patients with chronic schizophrenia when they were on stable doses of standard antipsychotics (Time I) and after they were stabilized on clozapine (Time II). A paired t-test was utilized to examine change in the NES factor measuring prefrontal functioning (three items testing complex motor sequencing plus memory) from Time I to Time II. There was a statistically significant improvement in scores on this factor (t(7)=4.25 p<.005) even though changes across time on the Brief Psychiatric Rating Scale and the Negative Symptom Assessment did not reach significance in this small sample. Analysis of each individual item showed that no item by itself improved significantly. This finding indicates a generalized improvement in cognitive function in patients on clozapine. Results suggest that either standard medications impair performance on these tests or that clozapine actually improves some areas of cognitive functioning. Either explanation holds hope for improved outcomes for patients on newer antipsychotics.
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Funderburg, L., True, J., Velligan, D. et al. Neurological changes with clozapine treatment. Neuropsychopharmacol 11, 269 (1994). https://doi.org/10.1038/sj.npp.1380149
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DOI: https://doi.org/10.1038/sj.npp.1380149