Sleep medication linked to safer outcomes than antipsychotics for older adults with delirium: Study

A large U.S. study suggests that older adults hospitalized with delirium may experience better outcomes when treated with trazodone, commonly used to treat depression and sleep problems, rather than commonly used antipsychotic medications. Delirium, a sudden state of confusion that often affects older adults during or after hospitalization, is frequently treated with medications despite limited evidence about which drugs are safest.

The study, “Safety outcomes of trazodone versus antipsychotics for delirium after hospital admission in adults aged 65 years and older,” was published in The Lancet Healthy Longevity. Researchers analyzed nationwide health data from adults aged 65 and older who were treated with medications for delirium following hospital admission. They compared patients who received trazodone with those prescribed atypical antipsychotic medications, such as quetiapine, risperidone, or olanzapine.

The findings showed that patients treated with trazodone had a lower risk of death and were less likely to be rehospitalized than those who received antipsychotic drugs. Importantly, the study did not find meaningful differences between the two groups in rates of falls or fractures — outcomes that are a significant concern for older adults taking sedating medications. The results suggest that trazodone may offer a safer alternative to antipsychotic drugs for managing delirium in older patients, particularly when medication use cannot be avoided.

To strengthen confidence in their results, researchers employed an advanced analytical approach known as target trial emulation, which is designed to make real-world observational data more closely resemble a randomized clinical trial. While the authors note that medications should never replace non-drug approaches to delirium care, the study provides important evidence to guide safer prescribing decisions.

“The lower risk of rehospitalization among patients treated with trazodone may be related to fewer hospital admissions for delirium and urinary tract infections,” said Dae Hyun Kim, MD, MPH, ScD, associate director and senior scientist at Hebrew SeniorLife’s Hinda and Arthur Marcus Institute for Aging Research. “By contrast, prior research has shown that antipsychotic medications are associated with greater cognitive decline and can affect the urinary system in ways that may raise the risk of urinary retention, incontinence, and infections. Although possibility of residual bias cannot be excluded, these effects may help explain why antipsychotics were linked to higher risks of delirium and rehospitalization in our study.”

Reference:

Yang, Chun-Ting et al., Safety outcomes of trazodone versus antipsychotics for delirium after hospital admission in adults aged 65 years and older: a nationwide cohort study using a target trial emulation framework, The Lancet Healthy Longevity, DOI: 10.1016/j.lanhl.2025.100804