Histamine H3 Receptor Antagonists for Alzheimer's Disease: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials

J Alzheimers Dis. 2015;48(3):667-71. doi: 10.3233/JAD-150393.


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.

Keywords: Alzheimer’s disease; histamine H3 receptor antagonist; meta-analysis; systematic review.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Histamine H3 Antagonists / therapeutic use*
  • Humans
  • Nootropic Agents / therapeutic use*
  • Randomized Controlled Trials as Topic


  • Histamine H3 Antagonists
  • Nootropic Agents