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Pharmacotherapy. 2019 May;39(5):530-543. doi: 10.1002/phar.2244. Epub 2019 Apr 8.

The Association Between Central Nervous System-Active Medication Use and Fall-Related Injury in Community-Dwelling Older Adults with Dementia.

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School of Pharmacy, University of Washington, Seattle, Washington.
Kaiser Permanente Washington Health Research Institute, Seattle, Washington.
Division of General Internal Medicine, University of Washington, Seattle, Washington.



To examine the association between central nervous system (CNS)-active medication use and the risk of fall-related injury in community-dwelling older adults following dementia onset. Further, to evaluate increased risk at higher doses or with a greater number of CNS-active medication classes.


Participants included community-dwelling older adults aged 65 years and older with a dementia diagnosis participating in the Adult Changes in Thought Study. From automated pharmacy data, a time-varying composite measure of CNS-active medication use was created. Central nervous system-active medication use was classified as current (use within prior 30 days), recent (prior 31-90 days), past (prior 91-365 days), and nonuse (no exposure in prior year). For current users, standardized daily doses (SDDs) were calculated for each CNS-active medication and summed across medications, and the number of CNS-active medication classes used was also measured. The outcome was fall-related injury based on emergency department, inpatient, and outpatient International Classification of Diseases, Ninth Revision (ICD-9) and external cause of injury (E) codes.


Among 793 subjects, 303 fall-related injuries occurred over a mean follow-up of 3.7 years (2907 total person-years). Relative to nonuse, fall risk was significantly higher for current use (adjusted hazard ratio [HR] 1.59, 95% confidence internal [CI] 1.19-2.12) but not for past or recent use. Among current users, increased risk was seen across SDD levels: HRs (95% CI): 1.77 (1.19-2.62), 1.79 (1.25-2.56), and 1.35 (0.96-1.92) for less than 1 SDD, 1 to less than 2 SDDs, and 2 or more SDDs, respectively (trend test, p=0.14). A trend was seen for increasing risk with a greater number of CNS-active medication classes; however, this was not statistically significant (trend test, p=0.084).


Current use of CNS-active medications was associated with fall-related injury in community-dwelling older adults followed from time of dementia onset, with increased risk even with use of low doses.


CNS-active agents; accidental falls; dementia


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