Dementia medications and risk of falls, syncope, and related adverse events: meta-analysis of randomized controlled trials

Abstract

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.

Figure 1. Study Selection.

Abbreviation: RCT, randomized controlled trial. * Not mutually exclusive.

Figure 2. Meta-Analysis of Cholinesterase Inhibitors and Falls, Syncope, and Related Events.*^†

Abbreviations: CI, confidence interval; Don, donepezil; Gal, galantamine; OR, odds ratio; Riv, rivastigmine; Tac, tacrine. * Pooled odds ratio and 95% confidence interval of each study are represented by a square and a horizontal line, respectively. The size of a square is proportional to the weight of the study. † I² measures the proportion of heterogeneity in individual studies that cannot be explained by chance.

Figure 3. Meta-Analysis of Memantine and Falls, Syncope, and Related Events.*^†

Abbreviations: CI, confidence interval; OR, odds ratio. * Pooled odds ratio and 95% confidence interval of each study are represented by a square and a horizontal line, respectively. The size of a square is proportional to the weight of the study. † I² measures the proportion of heterogeneity in individual studies that cannot be explained by chance.