Relation of Serum Anticholinergicity to Cognitive Status in Schizophrenia Patients Taking Clozapine or Risperidone

Background: A potential beneficial outcome of treatment with certain of the atypical neuroleptics is the reduced risk of cognitive impairment, stemming from purported low affinity for cholinergic receptors. In vitro experiments have shown that clozapine is highly anticholinergic and risperidone is minimally so. In vivo tests of the anticholinergic burden imposed by these medications and its potential cognitive consequences are needed. This study examines anticholinergic burden in schizophrenia patients taking clozapine and risperidone and tests whether this burden is associated with cognitive deficits.

Method: Serum anticholinergic levels were determined in a sample of 22 chronic schizophrenia patients using the radioreceptor assay method of Tune and Coyle (1980). Fifteen patients received clozapine; 7 received risperidone. Mean±SD age of the sample, comprising 12 men and 10 women (68% white), was 44.7±8.4 years. Mean±SD age at onset of schizophrenia illness was 23.5±7.4 years. Two anticholinergic assays based on blood samples collected 1 week apart were available on each patient.

Results: Data indicated that clozapine patients had significantly (p<.001) higher anticholinergic levels at both collection points, and levels for both drugs remained stable over time. The clozapine and risperidone patients had essentially equivalent scores on the cognitive measure.

Conclusion: These data suggest that anticholinergicity distinguishes clozapine and risperidone in vivo but that this effect is not associated with differences in global cognitive functioning. Results suggest that clozapine, despite producing moderately high in vivo serum anticholinergic levels, still holds clinical advantage over standard neuroleptics in terms of cognitive side effects. Reasons for this lowered risk of cognitive impairment are discussed.