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

Article type: Research Article

Authors: Kubo, Momoko | Kishi, Taro^* | Matsunaga, Shinji^* | Iwata, Nakao

Affiliations: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan

Correspondence: [*] Correspondence to: Taro Kishi, MD, PhD, Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan. Tel.: +81 562 93 9250; Fax: +81 562 93 1831; [email protected]

Correspondence: [*] Correspondence to: Shinji Matsunaga, MD, PhD, Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan. Tel.: +81 562 93 9250; Fax: +81 562 93 1831; [email protected]

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.

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

DOI: 10.3233/JAD-150393

Journal: Journal of Alzheimer's Disease, vol. 48, no. 3, pp. 667-671, 2015