Antihistamine use and the risk of injurious falls or fracture in elderly patients: a systematic review and meta-analysis

Summary: Despite their anticholinergic side effects, first-generation antihistamines are widely prescribed to elderly patients. A systematic review was conducted to synthesize real-world evidence. First-generation antihistamine use is considerably associated with an increased risk of injurious falls or fracture among the elderly. Introduction: First-generation antihistamines are considered potentially inappropriate for elderly patients owing to anticholinergic side effects. We aimed to determine whether elderly patients taking antihistamines are at increased risk of injurious falls or fracture. Methods: We identified studies in MEDLINE, EMBASE, and several local databases through November 2016. Observational studies on the association between antihistamine use and the risk of injurious falls or fracture were selected. Quality of the studies and the level of evidence were assessed. The random-effects model was employed for meta-analysis, and heterogeneity was examined based on I-square and Cochrane’s Q test. Subgroup analyses were performed when the heterogeneity among studies could not be explained. Results: From 473 identified studies, five (three case-control studies, one cohort study, and one case-crossover study) were included in our analysis based on eligibility criteria. First-generation antihistamine use showed significantly increased risk of injurious falls or fracture (odds ratio [OR] 2.03, 95% confidence interval [CI] 1.49–2.76, heterogeneity: p = 0.41, I² = 0%). Studies including antihistamines of all generations or containing no generation information were dealing with falls during hospitalization. Among these studies, the association was statistically significant without heterogeneity (OR 2.89, 95% CI 1.71–4.89, heterogeneity: p = 0.42, I² = 0%). Due to the small number of studies included and unadjusted results, meaningful interpretation based on subgroup analysis was limited. Conclusions: First-generation antihistamine use is considerably associated with increased risk of injurious falls or fracture among the elderly. Clinicians need to exercise caution when prescribing first-generation antihistamines to elderly patients.