Long-term benzodiazepine use is associated with poorer cognitive function in schizophrenia: findings from the SALT-C cohort

The association between long-term use of benzodiazepines (BDZs) and cognitive function in patients with schizophrenia has not been fully characterized. This study aimed to investigate the relationship between long-term BDZs use and cognitive function in schizophrenia.

Data were derived from an observational study of treatment with atypical antipsychotics in Chinese patients with schizophrenia (SALT-C). Fifty-seven patients with long-term use of BDZs (≥60 days) were included, and 57 BDZs non-users were matched using propensity scores for age, sex, disease duration, and atypical antipsychotics received. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA); psychotic symptoms, illness severity, and psychosocial functioning were assessed with the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression-Severity (CGI-S) scale, and the Personal and Social Performance (PSP) scale. Between-group comparisons were performed using independent-samples t-tests or Mann–Whitney U tests. Spearman correlation analysis was performed to assess the association between benzodiazepine dose and MoCA total scores among BDZ users.Factors associated with MoCA total scores were examined using multiple linear regression models.

The long-term BDZs user group showed a significantly lower total MoCA score [16.02 (6.69)] than the BDZs non-user group [19.33 (7.11)] (FDR-adjust p = 0.048). No significant between-group differences were observed in total scores on the PANSS, CGI-S, or PSP (all p > 0.05). No significant association was observed between benzodiazepines dose and MoCA scores (r = −0.098, p = 0.466). Multiple linear regression revealed that long-term BDZs use (β = −0.182, p = 0.008), PANSS total score (β = −0.217, p = 0.003) and anticholinergic burden (β = −0.199, p = 0.008) were independently associated with poorer cognitive performance, whereas years of education showed a positive association with cognitive performance (β = 0.460, p < 0.001).

Long-term BDZs use is associated with poorer cognitive performance in patients with schizophrenia, suggesting that cognitive function should be monitored and prolonged treatment avoided.