Double-blind, placebo-controlled, 4-way crossover study comparing the effects of doxepin 6 MG and zolpidem 10 MG on gait, balance, and cognitive performance in healthy volunteers.

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Conference Proceeding

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Falls are the leading cause of injury in older adults, accounting for millions of injuries. Frequency of nocturnal awakenings, sleep medication use, insomnia, and nocturia are independent risk factors for falls and hip fractures. To examine the effect of sleep medicine on gait and balance, we evaluated doxepin (DXP; Silenor®) 6mg (DXP6) and zolpidem 10mg (Z10), the highest doses indicated for insomnia. Additionally, the effects on memory were examined. Methods: This 4-way crossover study assessed the effects of a single dose of DXP6 compared with matching placebo and a single dose of Z10 compared with matching placebo at the respective Tmax in adult male volunteers (n = 39). Gait, balance, and memory were assessed 4 hou rs postdose for DX P6 and placebo and at 1.5 hours postdose for Z10 and placebo. After awakening, subjects performed the Tandem Walk (TW), the Berg Balance Scale (BBS) followed by immediate free recall while delayed recall was a ssessed 15 minutes after morning awakening. Results: Z10, but not DXP6, showed significantly poorer performance relative to placebo on all outcome measures. Also, in a direct comparison, performance on Z10 was impaired relative to DX P6. Measures that were significantly impaired (all p-values < 0.0001) for Z10 included TW #step-offs (500% more than DXP6), TW time to complete, BBS score, words recalled immediately and delayed (340% fewer words than DXP6). Conclusion: These data indicate that doxepin at the highest hypnotic dose (DXP6) did not cause impairment in gait, balance, or memory. In contrast, zolpidem at the highest hypnotic dose had broad CNS depressant effects. Functions as diverse as memory and balance were negatively impacted by Z10 directly or indirectly through its sedative activity. Further research is needed to determine if impairment is generalizable to other medications binding at the benzodiazepine receptor but not to drugs working on transmitters mediating wakefulness such histamine.



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