A recent double-blind, placebo-controlled randomized clinical trial conducted at 50 hospitals in Japan evaluated the efficacy of suvorexant, an orexin receptor antagonist, in reducing the incidence of delirium in older adults. The study, published in JAMA Network Open, aimed to determine whether suvorexant could reduce the incidence of delirium in hospitalized older adults at high risk for the condition.

The trial involved 203 participants aged 65 to 90 years who were at high risk for delirium due to mild cognitive impairment, mild dementia, or a history of delirium. Participants were randomly assigned to receive either suvorexant (15 mg) or a placebo nightly for up to 7 days during their hospitalization. Participants were stratified by reason for hospitalization (acute disease or elective surgery) and age category. The primary outcome was the incidence of delirium, diagnosed using the DSM-5 criteria.

The average age of participants was 81.5 years (standard deviation [SD] 4.5) in the suvorexant group and 82.0 years (SD 4.9) in the placebo group. In terms of gender distribution, the suvorexant group consisted of 52 men (51.5%) and 49 women (48.5%), while the placebo group included 45 men (44.1%) and 57 women (55.9%). Additionally, 93.1% of all participants had mild cognitive impairment or dementia.

The incidence of delirium was observed in 16.8% of participants in the group receiving suvorexant (17 out of 101), compared to 26.5% in the placebo group (27 out of 102), resulting in a difference of −8.7 percentage points (95% confidence interval [CI], −20.1% to 2.6%; P = .13). This primary endpoint did not reach statistical significance.

Secondary endpoints, including delirium and delirium severity assessed with DRS-R-98 scores, directionally favored suvorexant but were not statistically significant.

A post hoc analysis observed a difference in the occurrence of hyperactive and mixed subtypes of delirium between the suvorexant and placebo groups (10.9% vs 21.6%, P = .04), whereas the occurrence of hypoactive delirium was similar between groups.

Regarding safety, one death (due to urosepsis) occurred in the suvorexant group but was not considered drug-related. The overall incidence of adverse events was similar between groups. Events of clinical interest that occurred more frequently with suvorexant included falls, hypnagogic or hypnopompic hallucinations, and somnolence resulting in treatment discontinuation.

The study has several limitations. It was conducted exclusively in Japan, potentially limiting generalizability. The majority of participants had mild cognitive impairment or mild dementia, which may also limit generalizability. The 15 mg dose of suvorexant used is the maximum approved dose for older adults in Japan but is lower than the maximum dose approved in some other countries.

The authors concluded that while suvorexant may have potential benefits in reducing hyperactive delirium, further studies are needed to determine whether suvorexant may be useful for reducing delirium, particularly delirium with a hyperactive component, in this population.

Full disclosures can be found in the published study.