Treatment with lemborexant helps manage sleep disturbances in patients with liver cirrhosis, as shown in the crossover RESTORE* trial.
Over 2 weeks of treatment, sleep quality improved significantly with lemborexant but not with placebo. Mean Pittsburgh Sleep Quality Index (PSQI) scores decreased by 7 points with the 5-mg lemborexant dose (p<0.001), 8.27 points with the 10-mg dose (p<0.001), and 0.96 points with placebo (p=0.112). [Aliment Pharmacol Ther 2026;doi:10.1111/apt.70811]
After crossing over to lemborexant 5 mg, participants who initially received placebo achieved better sleep quality, with mean PSQI scores decreasing from 9 points at week 2 to 4.46 points at week 4 (mean change, −4.6 points; p<0.001).
On the other hand, participants who crossed over from either 5- or 10-mg lemborexant to placebo maintained their sleep quality, with no significant change in PSQI scores from weeks 2 to 4 (median change, 0 and 1 point, respectively; p=0.079 and p=0.160).
Favourable safety outcomes
There were no episodes of overt encephalopathy documented across all treatment periods.
Performance on the Stroop Test notably improved with 5-mg lemborexant, with mean scores decreasing by 23.5 points from baseline to week 2 (p<0.001). Conversely, a mild but significant increase in reaction time was observed with the 10-mg dose, with mean Stroop test scores increasing 16.7 points (p=0.048). Stroop test reaction time remained generally unchanged with placebo (median score change, –8.5 points; p=0.151).
The modest increase in Stroop test scores observed with the 10-mg dose was consistent with reports from previous studies, suggesting that lemborexant at higher doses might increase somnolence, despite being generally mild, according to the investigators.
Liver function test showed no significant within-group changes in ALT, AST, or total bilirubin levels across all treatment periods.
The lower-dose advantage
“To date, our clinical trial was the first trial demonstrating the efficacy of lemborexant specifically in patients with liver cirrhosis,” the investigators noted.
The findings, they said, support the use of the lower dose in patients with cirrhosis, for whom minimizing drug exposure and adverse effects are an important consideration.
“This is crucial, considering that previously, there had been no other pharmacologic therapy approved for patients with cirrhosis, which is a high-risk population due to the high prevalence of sleep problems and its significant clinical implications attributing to worsening neurocognitive impairment, lower quality of life, progression of liver dysfunction, increased hospitalization, and mortality,” they added.
RESTORE population
RESTORE included 82 patients with liver cirrhosis enrolled at Dr Cipto Mangukusumo Hospital in Jakarta, Indonesia. These patients were randomly assigned to receive treatment with lemborexant at 5 mg (n=28) or 10 mg (n=26) or placebo (n=28) for 2 weeks. Then, the patients who received lemborexant were crossed over to placebo, while those who received placebo were crossed over to lemborexant 5 mg for another 2 weeks (weeks 2–4).
The mean age of the patients was 56 years in the placebo and the 5-mg lemborexant groups and 52 years in the 10-mg dose group. Most participants were male (71.4 percent to 76.9 percent) and had Child–Pugh class A cirrhosis (75 percent to 84.6 percent). The prevalence of comorbidities, liver disease aetiology, and cirrhosis-related complications was similar across the treatment groups.
The investigators highlighted the need for larger randomized controlled trials with longer treatment duration and follow-up to establish the role of lemborexant in managing sleep disturbances for patients with liver cirrhosis.
“More objective measures of sleep such as polysomnography could be incorporated to corroborate our findings with subjective sleep quality,” they said. “Further research should also explore the implications of improved sleep on clinical outcomes such as quality of life, hospitalization, and mortality.”