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Antipsychotic Drugs Don't Ease ICU Delirium

A major study published Monday finds that widely prescribed antipsychotic drugs like haloperidol are no more effective than a placebo for treating delirium.
Nehru Sulejmanovski/Getty Images
A major study published Monday finds that widely prescribed antipsychotic drugs like haloperidol are no more effective than a placebo for treating delirium.

Powerful drugs that have been used for decades to treat delirium are ineffective for that purpose, according to a study published online Monday in the New England Journal of Medicine.

Antipsychotic medications, such as haloperidol (brand name, Haldol), are widely used in intensive care units, emergency rooms, hospital wards and nursing homes.

"In some surveys up to 70 percent of patients [in the ICU] get these antipsychotics," says Dr. E. Wesley "Wes" Ely, an intensive care specialist at Vanderbilt University Medical Center. They're prescribed by "very good doctors at extremely good medical centers," he says. "Millions of people worldwide are getting these drugs to treat their delirium."

But the drugs can have serious side effects. And Ely says there is no solid research showing that they are effective at treating delirium.

Patients with delirium are often confused and incoherent and sometimes can suffer hallucinations. This condition can lead to long-term cognitive problems, including a form of dementia.

Ely and colleagues at 16 U.S. medical centers decided to put antipsychotic drugs to a rigorous test. They divided nearly 600 patients who were suffering from delirium into three groups. One group got the powerful antipsychotic haloperidol. A second group got ziprasidone, which is a related medication from a class of drugs called "atypical antipsychotics." A third group got a placebo.

"The three groups did exactly the same," Ely says. There was no change in the duration of delirium, or the number of coma-free days. "They stayed in the ICU the same amount of time. They stayed on the mechanical ventilator the same amount of time. They didn't get out of the hospital any sooner."

"There's not a shred of evidence in this entire investigation that this aggressive approach to treating delirium with antipsychotics, which is commonplace and usual care, did anything for the patients," he concludes.

Ely was to present his results of the study, called MIND-USA, at the European Society of Intensive Care Medicine meeting in Paris today. Timed with that presentation, the New England Journal of Medicine published the paper online.

Ely says the drugs can calm patients down, and he still uses them at times for that purpose. They are also prescribed for severe depression, post-traumatic stress disorder, obsessive compulsive disorder and other mental health conditions. The new study only assessed the value of these drugs for treating delirium.

"This is huge!" says Dr. Juliana Barr, an anesthesiologist and intensive care specialist at Stanford University and the VA Palo Alto Medical Center who was not involved in the study. She has helped craft guidelines for appropriate drug use in the intensive care unit.

"I think the main take-home message is that providers really need to think differently about managing delirium in their patients in the ICU," she says. "A pill or an injection is really not a magic bullet for this devastating illness."

Barr expects the new study will change medical practice. "It's going to generate a sea change in how we think about best practices for managing delirium in the ICU," she says.

Both she and Ely advocate for a more holistic approach to treating delirium — getting patients off drugs and off breathing machines as soon as possible and getting them up and about as soon as they're able.

You can reach Richard Harris at rharris@npr.org.

Copyright 2021 NPR. To see more, visit https://www.npr.org.

Award-winning journalist Richard Harris has reported on a wide range of topics in science, medicine and the environment since he joined NPR in 1986. In early 2014, his focus shifted from an emphasis on climate change and the environment to biomedical research.
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