title: Histamine H3 Receptor Antagonists for Alzheimer's Disease: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.
abstract: BACKGROUND
  No comprehensive meta-analysis has been performed concerning the efficacy and tolerability of histamine H3 receptor antagonists (H3R-ANTs) in Alzheimer's disease patients.
  
  
  OBJECTIVE
  We performed a systematic review and meta-analysis of double-blind randomized placebo-controlled trials (RCTs) of H3R-ANTs for Alzheimer's disease.
  
  
  METHODS
  Relevant studies were identified through searches of PubMed, databases of the Cochrane Library, and PsycINFO citations up to June 19, 2015. The primary outcome was a change in the Mini-Mental State Examination (MMSE) scores. Secondary outcomes were Neuropsychiatric Inventory (NPI) scores, discontinuation rate, and individual adverse events/side effects. Risk ratios, numbers-needed-to-treat/harm, and standardized mean differences were calculated based on a random effects model.
  
  
  RESULTS
  The computerized search initially yielded 33 studies after excluding duplicates. We excluded 29 of these articles following a review of titles and abstracts and one RCT including healthy subjects after full-text review. We identified three RCTs (two on GSK239512 and one on ABT-288) including 402 patients. Pooled H3R-ANTs were not superior to placebo for improvement in MMSE and NPI scores. Discontinuation rate and individual adverse events/side effects did not differ among the pooled groups.
  
  
  CONCLUSIONS
  Our results suggest that H3R-ANTs are not effective in treating cognitive dysfunction in Alzheimer's disease. However, further studies with larger samples are required for definitive conclusions regarding responsive subpopulations.
authors.forename: Momoko
authors.initials: M
authors.lastname: Kubo
authors.forename: Taro
authors.initials: T
authors.lastname: Kishi
authors.forename: Shinji
authors.initials: S
authors.lastname: Matsunaga
authors.forename: Nakao
authors.initials: N
authors.lastname: Iwata
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D054828:Histamine H3 Antagonists / Q000627:therapeutic use*; D006801:Humans; D018697:Nootropic Agents / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
chemical_list: D054828:Histamine H3 Antagonists; D018697:Nootropic Agents
keywords: Alzheimer’s disease; histamine H3 receptor antagonist; meta-analysis; systematic review