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

Sep 30, 2026

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Study compares safety outcomes of trazodone versus atypical antipsychotic medications for delirium-related symptoms in older adults after hospital admission and discharge. Using US Medicare data (2013–2022) and Optum Clinformatics Data Mart (2013–2025) with a target trial emulation framework and propensity score overlap weighting across 162 covariates, the study assesses rehospitalisation and multiple clinical endpoints. In 11,678 trazodone and 29,590 antipsychotic users, trazodone shows lower risks for all-cause rehospitalisation, delirium rehospitalisation, urinary tract infection, and all-cause mortality, with no significant differences for falls, pneumonia, or stroke.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages17

Reading Time43 min

AccessFree to download

Summary

Background

Methods

Findings

Interpretation

Funding

Introduction

Author Manuscr ipt Author Manuscr ipt Author Manuscr ipt Author Manuscript | | HHS Public Access
Author manuscript
Lancet Healthy Longev. Author manuscript; available in PMC 2026 January 07. | | --- | --- | Published in final edited form as: Lancet Healthy Longev. 2025 December ; 6(12): 100804. doi:10.1016/j.lanhl.2025.100804 . 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 Chun-Ting Yang, James M Wilkins, Kevin T Pritchard, Qiaoxi Chen, Xiaojuan Liu, * Dae Hyun Kim , * Kueiyu Joshua Lin Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital (C-T Yang PhD, K T Pritchard PhD, Q Chen PhD, X Liu PhD, K J Lin MDScD), Division of Geriatric Psychiatry, McLean Hospital (J M Wilkins MD DPhil), Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife (D H Kim MD ScD), and Department of Medicine, Massachusetts General Hospital (K J Lin), Harvard Medical School, Boston, MA, USA; Division of Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA (D H Kim) Summary Background: Trazodone has emerged as a potentially safer alternative to atypical antipsychotic medications for managing delirium-related symptoms in older adults after hospital admission. This study aimed to compare safety outcomes in older adults who were prescribed trazodone versus atypical antipsychotic medication after hospital discharge. Methods: This population-based cohort study was done using US Medicare data from Jan 1, 2013, to Dec 31, 2022, and Optum de-identified Clinformatics Data Mart Database data from Jan 1, 2013, to Aug 31, 2025, with a target trial emulation framework. Patients aged at least 65 years without psychiatric disorders who were prescribed a new trazodone or atypical antipsychotic medication (quetiapine, risperidone, or olanzapine) prescription within 30 days of This is an open access article under the CC BY-NC-ND license ([http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/)). Correspondence to: Dr Kueiyu Joshua Lin, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, B*rCigohnamtribtd Wd eqmeallny’s Hospital, Harvard Medical School, Boston, MA 02120, USA, [jklin@bwh.harvard.edu](jklin@bwh.harvard.edu). Contributors C-TY did the literature search, wrote the first draft of the manuscript, and did all analyses. KJL acquired the data. C-TY, QC, and KJL had full access to the data as authorised under the data use agreements. Other authors did not have full access because they were not listed under these agreements. C-TY and KJL have directly accessed and verified the underlying data reported in the manuscript. KJL and DHK supervised the study and are the guarantors. All authors contributed to study conception, design, methods, result interpretation, and manuscript drafting. All authors approved the final manuscript and had final responsibility for the decision to submit. KJL attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. See Online for appendix Author Manuscr ipt Author Manuscr ipt Author Manuscr ipt Author Manuscript Yang et al. Page 2 hospital discharge with a claims-based delirium diagnosis were included. We applied propensity score overlap weighting to adjust for 162 covariates. The primary outcome was all-cause rehospitalisation. Secondary outcomes included rehospitalisation for delirium, falls (including fallrelated emergency department visits), pneumonia, urinary tract infections, stroke, and all-cause mortality. Treatment-outcome associations were estimated using the Fine–Gray model for nonfatal outcomes (presented as subdistribution hazard ratio [SDHR]) and the Cox model for all-cause mortality (presented as hazar

FAQs

What was the study’s primary goal?

To compare safety outcomes of trazodone versus atypical antipsychotic medications for older adults with delirium-related symptoms after hospital discharge.

What data sources and study design were used?

The study used US Medicare and Optum de-identified Clinformatics Data Mart data with a target trial emulation framework and propensity score overlap weighting.

Which safety outcomes showed a lower risk with trazodone?

Trazodone was associated with lower risks of all-cause rehospitalisation, rehospitalisation for delirium, urinary tract infection, and all-cause mortality compared with antipsychotics.

Sep 30, 2026

Uploaded by Grenda