Comparative efficacy and safety of quetiapine versus other atypical antipsychotics for behavioral and psychological symptoms in Alzheimer’s disease: a systematic review and meta-analysis

Background The management of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer’s disease (AD) remains a significant challenge. While atypical antipsychotics are used, their comparative efficacy and safety, particularly for quetiapine, are not well-established within a homogeneous AD population. This meta-analysis aimed to directly compare the efficacy and safety of quetiapine versus other active pharmacological agents (primarily risperidone and olanzapine) for BPSD specifically in patients with AD. Methods A systematic search of PubMed, Embase, Cochrane Library, Web of Science, CNKI, and WanFang databases was conducted up to March 15, 2024, for randomized controlled trials (RCTs). The primary efficacy outcome was treatment failure (lack of clinical improvement). Safety outcomes included specific adverse events. Data were pooled using random-effects models to calculate odds ratios (ORs) with 95% confidence intervals (CIs). Results Twenty-five RCTs involving 2143 participants were included. The pooled analysis of 16 studies (n=1384) demonstrated that quetiapine was associated with significantly lower odds of treatment failure compared to other atypical antipsychotics (OR 0.66, 95% CI 0.49 to 0.89, P = 0.006). In pre-specified subgroup analyses, quetiapine showed significant superiority over risperidone (OR 0.50, 95% CI 0.33 to 0.75, P = 0.0009) and a non-significant trend favoring quetiapine over olanzapine (OR 0.90, 95% CI 0.58 to 1.38, P = 0.62). Regarding safety, quetiapine was associated with a substantially and significantly lower risk of extrapyramidal symptoms (EPS) (OR 0.17, 95% CI 0.09 to 0.33, P<0.00001). No significant differences were found for other common adverse events such as somnolence, dizziness, or constipation. Conclusion This meta-analysis suggests that quetiapine may offer a potential efficacy advantage for alleviating BPSD in patients with AD, particularly when compared to risperidone, while demonstrating comparable overall effectiveness to other atypicals. Its most distinguishing feature is a substantially lower risk of extrapyramidal symptoms. Interpretation of these findings must be tempered by the moderate risk of bias in constituent trials, the necessary harmonization of disparate efficacy metrics, and the scarcity of long-term safety data. Quetiapine may serve as a neurologically better-tolerated option when non-pharmacological strategies are insufficient, pending careful, time-limited use.