Treatment of Restless Legs Syndrome Improves Agitation and Sleep in Persons with Dementia: A Randomized Trial

Abstract

Objectives

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.

Design

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.

Setting and Participants

Older adults (N = 147) with dementia due to Alzheimer's disease, nighttime agitation, and RLS, residing in long-term care or at home, participated.

Methods

The primary outcome was change from baseline to 8 weeks 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.

Results

Mean age ± SD was 83.4 ± 9.1 years. 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 8 weeks (estimate, −1.67; P = .003) and 2 weeks. Total sleep time (actigraphy) by group over time was significant at 8 weeks (estimate, 48.45; P = .026). Observed nighttime wake by group over time was significant at 2 (estimate, −12.54; P = .006) and 8 weeks (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).

Conclusions and Implications

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.