Efficacy, acceptability and tolerability of second-generation antipsychotics for behavioural and psychological symptoms of dementia: a systematic review and network meta-analysis.

Background: Behavioural and psychological symptoms of dementia (BPSD) are highly prevalent in people living with dementia. Second-generation antipsychotics (SGAs) are commonly used to treat BPSD, but their comparative efficacy and acceptability are unknown.

Methods: The standard mean difference (SMD) was used to pool the fixed effects of continuous outcomes. We calculated ORs with corresponding 95% credible intervals (CI) for the categorical variable. Efficacy was defined as the scores improved on the standardised scales. Acceptability was defined as the all-cause dropout rate. Tolerability was defined as the discontinuation rate due to adverse effects (AEs). The relative treatment rankings were reported with the surface under the cumulative curve. The AE outcomes included mortality, cerebrovascular adverse events (CVAEs), falls, sedation, extrapyramidal symptoms and urinary symptoms.

Results: Twenty randomised controlled trials with a total of 6374 individuals containing 5 types of SGAs (quetiapine, olanzapine, risperidone, brexpiprazole and aripiprazole) with intervention lengths ranging from 6 weeks to 36 weeks were included in this network meta-analysis. For the efficacy outcome, compared with the placebo, brexpiprazole (SMD=-1.77, 95% CI -2.80 to -0.74) was more efficacious, and brexpiprazole was better than quetiapine, olanzapine and aripiprazole. Regarding acceptability, only aripiprazole (OR=0.72, 95% CI 0.54 to 0.96) was better than the placebo, and aripiprazole was also better than brexpiprazole (OR=0.61, 95% CI 0.37 to 0.99). In terms of tolerability, olanzapine was worse than placebo (OR=6.02, 95% CI 2.87 to 12.66), risperidone (OR=3.67, 95% CI 1.66 to 8.11) and quetiapine (OR=3.71, 95% CI 1.46 to 9.42), while aripiprazole was better than olanzapine (OR=0.25, 95% CI 0.08 to 0.78). Quetiapine presented good safety in CVAE. Brexpiprazole has better safety in terms of falls and showed related safety in sedation among included SGAs.

Conclusion: Brexpiprazole showing great efficacy in the treatment of BPSD, with aripiprazole showing the highest acceptability and olanzapine showing the worst tolerability. The results of this study may be used to guide decision-making.