Dementia Medications and Risk of Falls, Syncope, and Related Adverse Events: Meta-Analysis of Randomized Controlled Trials

OBJECTIVES: To evaluate the effect of cholinesterase inhibitors (ChEIs) and memantine on the risk of falls, syncope, and related events, defined as fracture and accidental injury. DESIGN: Meta-analysis of randomized controlled trials that were identified from MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (no language restriction, through July 2009), and manual search. SETTING: Community and nursing homes. PARTICIPANTS: Participants in fifty-four placebo-controlled randomized trials and extension studies of ChEIs and memantine that reported falls, syncope, and related events in cognitively impaired older adults. MEASUREMENTS: Falls, syncope, fracture, and accidental injury. RESULTS: ChEI use was associated with greater risk of syncope (odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.02-2.30) than placebo but not with other events (falls: OR = 0.88, 95% CI = 0.74-1.04; fracture: OR = 1.39, 95% CI = 0.75-2.56; accidental injury: OR = 1.13, 95% CI = 0.87-1.45). Memantine use was associated with fewer fractures (OR = 0.21, 95% CI = 0.05-0.85) but not with other events (falls: OR = 0.92, 95% CI = 0.72-1.18; syncope: OR = 1.04, 95% CI = 0.35-3.04; accidental injury: OR = 0.80, 95% CI = 0.56-1.12). There was no differential effect according to type and severity of cognitive impairment, residential status, or length of follow-up, although because of underreporting and small number of events, a potential benefit or risk cannot be excluded. CONCLUSION: ChEIs may increase the risk of syncope, with no effects on falls, fracture, or accidental injury in cognitively impaired older adults. Memantine may have a favorable effect on fracture, with no effects on other events. More research is needed to confirm the reduction in fractures observed formemantine. J AmGeriatr Soc 59:1019-1031, 2011.