Pharmacological treatment of neuropsychiatric symptoms in Alzheimer's disease: a systematic review and meta-analysis

J Neurol Neurosurg Psychiatry. 2015 Jan;86(1):101-9. doi: 10.1136/jnnp-2014-308112. Epub 2014 May 29.


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.

Keywords: Alzheimer's Disease; Meta-Analysis; Neuropsychiatry; Systematic Reviews.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Alzheimer Disease / complications
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / psychology*
  • Humans
  • Mental Disorders / complications*
  • Mental Disorders / drug therapy*
  • Mental Disorders / psychology
  • Patient Dropouts / statistics & numerical data
  • Psychotropic Drugs / adverse effects
  • Psychotropic Drugs / therapeutic use*
  • Randomized Controlled Trials as Topic / statistics & numerical data


  • Psychotropic Drugs