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.
