New Study Compares Risks for Antipsychotic Drugs After Major Surgery for Older Adults

Researchers recommend implementing non-pharmacological strategies to prevent post-operative delirium.

BOSTON, MA – A new study published in the Annals of Internal Medicine that compared different antipsychotics used to treat symptoms of post-operative delirium in older patients found that the risks of commonly prescribed atypical antipsychotic drugs such as olanzapine, quetiapine, and risperidone, were not safer than haloperidol in combatting delirium.

Post-operative delirium is the most common post-operative complication in older adults, and is associated with longer hospital stays, institutional discharge, decline in function, mortality, and increased healthcare costs. Doctors have prescribed off-label use of atypical antipsychotic drugs such as olanzapine, quetiapine, and risperidone, to address delirium symptoms because they were often considered less harmful than haloperidol.

However, after examining hospital administrative data for 17,115 patients aged 65 and older without psychiatric disorders who were prescribed an oral antipsychotic drug after major surgery from 2009 to 2018, this observational study, “Comparative Safety Analysis of Oral Antipsychotics for In-Hospital Adverse Clinical Events in Older Adults After Major Surgery,” found the risk for in-hospital deaths, cardiac arrhythmia events, pneumonia, and stroke were similar across haloperidol and atypical antipsychotic drugs.

The study found no statistically significant difference in the risk for in-hospital death among patients treated with haloperidol, olanzapine, quetiapine, and risperidone. The risk for nonfatal clinical events ranged from 2.0% to 2.6% for a cardiac arrhythmia event, 4.2% to 4.6% for pneumonia, and 0.6% to 1.2% for stroke or transient ischemic attack, with no significant difference between the drugs. 

“Based on a decade’s worth of data we reviewed, we’ve concluded that because there is no safer antipsychotic drug option, we should focus on implementing safe, non-pharmacological strategies to prevent postoperative delirium, and reducing off-label antipsychotic drug use altogether,” said Dae Hyun Kim, M.D., MPH, ScD, associate scientist, Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, associate professor of medicine, Harvard Medical School, and lead author of the study. “As proven by the Hospital Elder Life Program, developed by Dr. Sharon Inouye at Hebrew SeniorLife, non-pharmacological strategies, such as cognitive stimulating activities, frequent orientation, regular mobility, nutrition, hydration, and sleep hygiene, can safely reduce delirium in the hospitalized older adults.”

Brigham and Women’s Hospital, Beth Israel Deaconess Medical Center, Vanderbilt University Medical Center, Yale University, Stanford University, and Brown University collaborated in this retrospective cohort study.

Co-authors of the study include Su Been Lee, research assistant at Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital; Chanmi Park, M.D., MPH, post-doctoral research fellow at the Marcus Institute; Raisa Levin, M.S., sr. programmer/analyst at Brigham and Women's Hospital; Eran Metzger, M.D., medical director of psychiatry at Hebrew SeniorLife; Brian T. Bateman, M.D., ScM, professor and chair, Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine; E. Wesley Ely, M.D., MPH, professor of medicine and critical care, associate director of aging research, VA GRECC; Pratik P. Pandharipande, M.D., MSCI, professor of anesthesiology and surgery, Vanderbilt University Medical Center; Margaret A. Pisani, M.D., MPH, professor of internal medicine, Yale University School of Medicine; Richard N. Jones, ScD, professor, Department of Psychiatry and Human Behavior, Department of Neurology, Warren Alpert Medical School, Brown University; Edward R. Marcantonio, M.D., ScM, section chief for  research, Division of General Medicine, Beth Israel Deaconess Medical Center, professor of medicine, Harvard Medical School; and Sharon K. Inouye, M.D., MPH, professor of medicine at Harvard Medical School, the Milton and Shirley F. Levy Family chair and director of the Aging Brain Center at the Hinda and Arthur Marcus Institute for Aging Research.

Funding came from grants from National Institute on Aging of the National Institutes of Health under award numbers R01AG056368 and R33AG071744.

About Hebrew SeniorLife
Hebrew SeniorLife, an affiliate of Harvard Medical School, is a national senior services leader uniquely dedicated to rethinking, researching, and redefining the possibilities of aging. Hebrew SeniorLife cares for more than 4,500 seniors a day across six campuses throughout Greater Boston. Locations include: Hebrew Rehabilitation Center-Boston and Hebrew Rehabilitation Center-NewBridge in Dedham; NewBridge on the Charles, Dedham; Orchard Cove, Canton; Simon C. Fireman Community, Randolph; Center Communities of Brookline, Brookline; and Jack Satter House, Revere. Founded in 1903, Hebrew SeniorLife also conducts influential research into aging at the Hinda and Arthur Marcus Institute for Aging Research, which has a portfolio of more than $85 million, making it one of the largest gerontological research facilities in the U.S. in a clinical setting. It also trains more than 1,000 geriatric care providers each year. For more information about Hebrew SeniorLife, visit our website or follow us on our blog, Facebook, Instagram, Twitter, and LinkedIn.

About the Hinda and Arthur Marcus Institute for Aging Research
Scientists at the Marcus Institute seek to transform the human experience of aging by conducting research that will ensure a life of health, dignity, and productivity into advanced age. The Marcus Institute carries out rigorous studies that discover the mechanisms of age-related disease and disability; lead to the prevention, treatment, and cure of disease; advance the standard of care for older people; and inform public decision-making.