Atypical Antipsychotics for Neuropsychiatric Symptoms in Alzheimer’s Disease: A Systematic Review and Meta-Analysis
Letícia Saldanha1, Giovanna Salema Pascual2, Pedro Henrique Reginato3, Vinicius Castro4, Gabriel Mantovani5, Leonardo Pipek4
1Federal University of Ceará, 2University of Bologna, 3Federal University of Paraná, 4University of São Paulo, 5Clinical Hospital of Porto Alegre
Objective:
To evaluate the use of atypical antipsychotics in the treatment of neuropsychiatric symptoms (NPS) in patients with Alzheimer’s disease (AD).
Background:
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.
Design/Methods:
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.
Results:
This study included a total of 17 RCTs with 5.018 patients, of whom 3.093 (61,64%) received either aripiprazole, brexpiprazole, olanzapine, pimavanserin, quetiapine or risperidone. Atypical antipsychotics were associated with significant improvement in CMAI (MD = -3.24; [-4.66, -1.82]; p<0.00001; I²=0%). On the other hand, there was no statistically meaningful difference between groups in MMSE (MD = -0.29; [-0.71, 0.12]; p=0.16; I²=54%), SAEs (OR = 1.19 [0.92 , 1.54]; p=0.20; I²=0%) and all-cause mortality (OR = 1.39 [0.90 , 2.15]; p=0.14; I²=0%).
Conclusions:
Our findings indicate that atypical antipsychotics can be used for management of NPS in patients with AD, reducing the severity and incidence of agitation, without increasing SAEs and all-cause mortality. However, these drugs were not associated with the improvement in cognitive impairment.
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