A systematic review and meta-analysis of the effect of clozapine on cognitive functions in patients with treatment-resistant schizophrenia

This study aimed to conduct a systematic review and meta-analysis on cognitive performances of patients with treatment-resistant schizophrenia (TRS) after clozapine treatment and to examine the potential effect of follow-up duration and clozapine dosage. Five electronic databases were searched and studies were included if treatment-resistant schizophrenia patients were treated with clozapine and with baseline and follow-up cognitive functions assessments. Cognitive measures were categorised into six domains based on DSM-5-TR. Random-effect model analysis was used to pool the effect estimates. Moderator effects of clozapine dosage, follow up duration, duration of illness, age, years of education and change in positive symptoms severity were examined with meta-regression. Nineteen articles were included with 50 cognitive measures reported. Systematic review found inconsistent results. Twelve cognitive measures were included for meta-analysis and found overall improvement of cognitive performances after clozapine treatment SMD = 0.11 [95 % CI 0.02, 0.20] (p = 0.021). Patients with younger age, more years of education and improvements in positive symptoms are more likely to improve in cognitive performances. Subgroup analysis found significant improvement in studies with follow-up periods of 6-months or longer but not for studies with shorter follow-up periods. Clozapine may improve some domains of cognitive function, particularly over a longer period. However, the overall inconsistent results suggest that more studies with larger sample size and standard cognitive function assessments would be needed to enhance our understanding of the impact of clozapine on the cognitive functions in the TRS patients.