Restless legs syndrome (RLS), a common, treatable, sensorimotor disorder of nighttime uncomfortable leg sensations that interfere with sleep, may prompt nighttime agitation in persons with dementia. This randomized trial was double-blind and placebo-controlled. Participants received a Food and Drug Administration-approved drug for RLS, gabapentin enacarbil (GEn) (Horizant) or placebo. Older adults (N= 147) with dementia due to Alzheimer's disease, nighttime agitation, and RLS, residing in long-term care or at home, participated. The primary outcome was change from baseline to 8weeks in nighttime agitation between 5 pm and 7 am on the Cohen-Mansfield Agitation Inventory Index, Direct Observation. Multivariable linear mixed effects regression models based on multiply imputed data were estimated on nighttime agitation and sleep, with treatment group, week, the 2-way interaction of group and week as predictors, and mean arterial pressure as a covariate based on baseline group imbalances. Mean age ± SD was 83.4 ± 9.1years. Most were female (72.0%), White (92.3%), non-Hispanic (84.6%), and lived in nursing homes (76.9%). Nighttime agitation, by group over time, was significant at 8weeks (estimate,-1.67; P= .003) and 2weeks. Total sleep time (actigraphy) by group over time was significant at 8weeks (estimate, 48.45; P= .026). Observed nighttime wake by group over time was significant at 2 (estimate,-12.54; P= .006) and 8weeks (estimate,-11.12; P= .015). The number having ≥1 adverse events was 60 in the GEn group (81.1%) and 50 in the placebo group (68.5%); with 12 serious adverse events in placebo and 10 in the GEn group. The GEn group had a trend toward more falls (P=.066). Our findings suggest a novel approach for nighttime agitation in persons with dementia: assessing for RLS and initiating interventions. Larger and longer trials are needed.
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