Can Methylphenidate Reduce Fall Risk in Community-Living Older Adults?  A Double-Blind, Single-Dose Cross-Over Study

Background:  Falls are one of the leading causes of morbidity and mortality among older adults, and though much is known about the reasons why these falls occur, alternative measures need to be studied to help reduce their occurrences.

Objective:  To assess whether cognitive intervention with methylphenidate (MPH) is a means to help modify markers associated with fall risk among older adults.

Methods:  The study utilized a randomized, double-blind, placebo-controlled, cross-over design.  It was conducted over a two week period.  Twenty-six patients, aged 65 to 90, with self-admitted memory problems and the ability to ambulate independently without the use of a walking aid were included in the study.  The exclusion criteria included patients with dementia; patients with clinically significant musculoskeletal, cardiovascular, respiratory, or vestibular disorders; and patients with a history of significant head trauma, Parkinson’s or other neurodegenerative diseases, major depression, or uncorrected visual problems.  Due to the side effect profile of MPH, patients with glaucoma, uncontrolled high blood pressure, heart failure, or cardiac arrhythmias; patients with a history of epilepsy; and patients taking mono-amine oxidase inhibitors or tricyclic antidepressants were also excluded.  The treatment regimens consisted of single-doses of either methylphenidate 20mg or placebo.  The primary outcome measure was a fall risk screening test called the Timed Up and Go, and the secondary measure was stride time variability.  Executive function was measured using two tests, the Go-NoGo and the Catch Game.  Power was not reported for this study.

Results:  Data from all 26 patients was analyzed and included in the results of the study.  Timed Up and Go times were decreased to 9.4 ± 0.5 seconds with MPH and 9.9 ± 0.6 seconds with placebo (p = 0.03).  Stride time variability percentages where reduced to 2.72 ± 0.24 with MPH and 3.08 ± 0.32 with placebo (p = 0.55).  The Go-NoGo accuracy value was increased to 94.5% ± 1.5% with MPH and 90%.0 ± 2.65% with placebo (p = 0.03).  Catch Game accuracy scores where increased to 494.1 ± 43.4 and 485.1 ± 50.9 in the MPH and placebo groups respectively (p = 0.68).  Times in the Catch Game time to first move test decreased to 850.4 ± 49.4ms with MPH, and increased to 902.4 ± 44.5ms with placebo (p = 0.20).  No adverse events were reported.

Strengths:  This study showed similar findings when compared to other previous studies where MPH was shown to improve gait speed, Timed Up and Go times, stride time variability, and executive function.  Randomization and blinding were appropriately handled since the investigators as well as the patients had no knowledge of the contents of the pills during the study, and the information pertaining to that was not revealed to the investigators until after analysis of the data.

Weaknesses:  This study utilized a cross-over design which may sometimes lead to carry-over effects and longer study durations.  Results were reported in means ± standard errors instead of standard deviations.  The list of exclusion criteria limited the ability of the study data to be extrapolated to the true population it was intending to encompass.  The study consisted of a very small sample size and it neglected to report a power.  Only one dose of MPH was used.  Possible side effects from other doses or other durations of therapy were not determined.  The study showed a statistical significance in a few of the markers studied, but the small units used for these markers (eg. milliseconds) may not translate in to a clinical significance.

Conclusion:  The study did show that MPH improved certain markers of fall risk; however the significance of how much they improved them over placebo was not adequately shown.  The authors explained the key limitations to the study, and through these limitations they realized that further investigation needs to be done in order to better understand the true capability of MPH as an aid to help limit fall risk.  Additional studies using parallel groups, longer durations of therapy, different doses of MPH, or less stringent exclusion criteria could help to determine this information.

Ben-Itzhak R, Giladi N, Gruendlinger L, Hausdorff JM. Can methylphenidate reduce fall risk in community-living older adults? A double-blind, single-dose cross-over study.  J Am Geriatr Soc. 2008 Apr;56(4):695-700.

Chris Costelnock, Pharm.D. Candidate

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