Effects of Clozapine on Neurocognitive Functions in Schizophrenia: A Naturalistic Comparison to Non-clozapine Antipsychotics

OBJECTIVE: While clozapine is recognized as the most effective antipsychotic for individuals with treatment-resistant schizophrenia, its effects on neurocognition remain unclear. This study aimed to compare the neurocognitive effects of clozapine treatment to those of non-clozapine antipsychotics in patients with schizophrenia and to examine the role of anticholinergic burden on cognitive impairments. DESIGN: This was a naturalistic study. Cross-sectional data were drawn from participants with chronic schizophrenia in two clinical trials assessing cognition. Cognition was evaluated using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB). Anticholinergic burden was calculated for each medication using the Anticholinergic Cognitive Burden (ACB) scoring system. We stratified the participants treated with non-clozapine antipsychotics into high ACB score versus low ACB score groups. RESULTS: One hundred and seventy participants were enrolled and treated with clozapine (n=58) or non-clozapine antipsychotics (n=112). We observed no significant differences in the MCCB T-scores between the clozapine and the total non-clozapine groups for the cognitive composite score and the seven domain scores. However, the non-clozapine high ACB group showed significant impairments in processing speed and attention/vigilance, in contrast to the non-clozapine low ACB group (p