Alzheimer’s disease is a neurodegenerative disorder that progressively impairs behavioral and cognitive functions, being characterized by neuropsychiatric symptoms, that may include agitation, apathy, psychosis, delusions and hallucinations. Atypical antipsychotics are used to treat NPS in AD, but there are concerns about the cognitive impact and the long-term safety of them.

We searched PubMed, Embase and Cochrane Library to identify randomized controlled trials (RCTs) comparing atypical antipsychotics with placebo in patients with any NPS in AD, with no restrictions on time of follow-up. The protocol was registered in PROSPERO (CRD42024544024). We assessed the severity and frequency of agitated behaviors through Cohen-Mansfield Agitation Inventory (CMAI), as the primary outcome. The secondary outcomes were the degree of cognitive impairment through Mini-Mental State Examination (MMSE), the occurrence of serious adverse events (SAEs) and all-cause mortality. Statistical analysis was performed using RevMan 8.7.0. Heterogeneity was assessed with I² statistics.