Less Nausea After Surgery: Olanzapine Tested in Clinical Trial

Many people feel that the worst part of surgery happens after they wake up. Countless patients who undergo general anesthesia worry about nausea and vomiting, common side effects after surgery. A clinical trial by Yale School of Medicine’s Department of Anesthesiology reveals that a small dose of olanzapine, an inexpensive antipsychotic medication, could curb those symptoms. The treatment could also ensure smoother post-surgical recovery.

The trial, published in Anesthesiology, shows that a single 5 milligram dose of olanzapine before surgery improved overall recovery. It also reduced nausea in patients discharged after ambulatory surgery. Ambulatory surgery allows patients to go home the same day, which makes it that much more important to prevent nausea from following them out the door.

The investigator-initiated trial was led by Jaime B. Hyman, MD, associate professor of anesthesiology and division chief of ambulatory anesthesiology, who served as principal investigator, and John Guzzi, MD, assistant professor of anesthesiology, who was the study’s first author.

Quality of recovery after surgery includes a number of factors that affect patient comfort, nausea being chief among them.

“For patients, nausea after surgery is among the worst feelings,” says Guzzi. “For same-day surgery, it’s the number-one thing that holds people back and causes them to call their surgeons or re-present to the hospital. If you go home from ambulatory surgery and find that you can’t keep your food down, can’t do your usual activities, or return to work as anticipated—this affects a lot of people.”

Guzzi has been passionate about addressing postoperative nausea and vomiting since his time as an anesthesiology resident at Yale. Working with Hyman, he helped translate that interest into a rigorous clinical trial focused not only on nausea, but also on patients’ overall quality of recovery. Their shared emphasis on patient-centered outcomes is now driving efforts to bring the findings into clinical practice across the health system.

Olanzapine is a medication that has traditionally been used to treat conditions such as schizophrenia and bipolar disorder, but it has also been shown to reduce nausea and vomiting associated with surgery or chemotherapy. Although it is also known to limit nausea after an operation, past studies have shown that a 10 milligram dose of the drug before surgery may also increase tiredness among patients after surgery.

The research team tested whether a lower 5 milligram dose of olanzapine before surgery could not only reduce nausea and vomiting, but also improve the patient’s overall recovery quality. The team looked at patient-centered outcomes of recovery, including comfort, emotional well-being, pain, and others.

“We designed the study to answer a practical question: Could a lower dose preserve olanzapine’s anti-nausea benefits without compromising the broader recovery experience that matters to patients?” says Hyman. “Rather than looking only at whether patients experienced nausea, we wanted to understand how they actually felt and functioned after they went home.”

Guzzi adds, “I was hopeful we would see something in these patient-centered outcomes, but to find a clinically significant difference to this extent, was surprising, even for us. There are very, very few medications that have shown this degree of impact on recovery as a single intervention.”

Compared with a placebo, those who received 5 milligrams of olanzapine had a better overall recovery. This went beyond a lower risk of nausea.

With the magnitude of effect shown in the results from the clinical trial, the research team is confident that these findings will improve the recovery period for at-risk patients undergoing ambulatory surgery. This change could allow for more patients to fully recover at home without having to return to the hospital.

“We know olanzapine works for our patients. Now we need to make sure those patients are able to get the medicine,” says Guzzi. “We need to make sure that patients that should be getting this medicine are able to without delaying their surgical care. We don't want to add too many steps into the workflow for their care teams.”

Looking ahead, the team is already planning the next phase of this work. Hyman, Guzzi and Adriana Herrera, MD, assistant professor of anesthesiology and co-author on the study, want to implement the usage of preoperative olanzapine on a broader scale, enhancing the recovery process for patients throughout the health system.

Wider access to this medication for people preparing for surgery will improve comfort after surgery, benefiting patients across Yale’s delivery networks. The upcoming implementation of olanzapine will help more people focus on healing after surgery instead of battling queasiness.

In addition to Hyman, Guzzi, and Herrera, the other Yale authors are Claudia Fernandez Robles, MD; Xiwen Zhao, MSPH; Tiana Fernandez, BS; Aryana Valedon, BA; Christopher Tanaka, BA; Selma Belkasim, MS; and Hung-Mo Lin, ScD. Other authors include: Tom Gugel, APRN; Megan Longley, MS; Andrew Shapiro, BA; Alicia Stephan, MD; and Marguerite Gilmore, BA.