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 for memantine.