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Research paper
Pharmacological treatment of neuropsychiatric symptoms in Alzheimer's disease: a systematic review and meta-analysis
  1. Jun Wang1,
  2. Jin-Tai Yu1,2,
  3. Hui-Fu Wang2,
  4. Xiang-Fei Meng1,
  5. Chong Wang1,
  6. Chen-Chen Tan1,
  7. Lan Tan1,2
  1. 1Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China
  2. 2Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China
  1. Correspondence to Dr Jin-Tai Yu, Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No.5 Donghai Middle Road, Qingdao, Shandong Province 266071, China; yu-jintai{at}


Background A wide variety of pharmacological agents are used in the management of neuropsychiatric symptoms, which are common in Alzheimer's disease (AD), but results from randomised controlled trials (RCTs) on the efficacy and safety of these agents are conflicting.

Objectives To quantify the efficacy and safety of pharmacological treatment on neuropsychiatric symptoms in AD patients.

Methods Systematic review and meta-analysis of RCTs comparing pharmacological agents with placebo on Neuropsychiatric Inventory (NPI) and safety outcomes in AD patients with neuropsychiatric symptoms.

Results Cholinesterase inhibitors (ChEIs) and atypical antipsychotics improved NPI total scores (ChEIs: standardised mean difference (SMD) −0.12; 95% CI −0.23 to −0.02; atypical antipsychotics: SMD −0.21; 95% CI −0.29 to −0.12), but antidepressants (95% CI −0.35 to 0.37) and memantine (95% CI −0.27 to 0.03) did not. However, ChEIs and atypical antipsychotics increased risk of dropouts due to adverse events (ChEIs: risk ratio (RR) 1.64; 95% CI 1.12 to 2.42; atypical antipsychotics: RR 2.24; 95% CI 1.53 to 3.26) and on incidence of adverse events (ChEIs: RR 1.08; 95% CI 1.01 to 1.17; atypical antipsychotics: RR 1.17; 95% CI 1.05 to 1.31). For typical antipsychotics, no study was included.

Conclusions ChEIs and atypical antipsychotics could improve neuropsychiatric symptoms in AD patients, but with bad safety outcomes.

  • Alzheimer's Disease
  • Meta-Analysis
  • Systematic Reviews
  • Neuropsychiatry

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