Antipsychotic Drugs Don't Ease ICU Delirium

Oct 22, 2018
Originally published on October 23, 2018 9:52 am

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.

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AUDIE CORNISH, HOST:

For 40 years, doctors have been prescribing powerful antipsychotic drugs to patients suffering from delirium. Haldol is a common one. But a sweeping new study finds those drugs are completely ineffective in treating delirium. The study was published online today in The New England Journal of Medicine. NPR's Richard Harris reports.

RICHARD HARRIS, BYLINE: Every intensive care unit nurse encounters delirious patients like Brian, a 47-year-old man who had been admitted to the ICU at Vanderbilt University Medical Center with a failing liver. When doctors swing through on a recent morning on their daily rounds, nurse Lindsey Smith recaps Brian's rough night.

LINDSEY SMITH: He is completely disoriented this morning. He couldn't even tell me his name. Mobility-wise, he can move all of his extremities. He's tried to get out of bed several times this morning. We ended up having to restrain him because the mittens were not getting over his hands.

HARRIS: In his confused, delirious state, he doesn't realize that the IV lines are actually providing him much-needed medicine.

SMITH: He has two peripheral IVs. Those are switching positions 'cause he keeps pulling them out.

WES ELY: Let's go see him.

HARRIS: Dr. Wes Ely and the team head into the room. He's concerned about bringing this man's delirium under control. If it persists, it can greatly increase the risk he will suffer long-term problems thinking and remembering.

ELY: Brian, hi. I'm Dr. Ely. How are you doing?

BRIAN: I'm all right.

ELY: What's the main thing bothering you today?

HARRIS: Brian can't seem to make sense of the question. Ely persists.

ELY: Hold up that many fingers. Hold it up with your hand.

HARRIS: Brian can't follow that simple command either. Ely says these are signs of delirium. Many doctors would give him a powerful antipsychotic such as Haldol or a related drug called ziprasidone. The assumption for decades is that these drugs could treat delirium.

ELY: In some surveys, up to 70 percent of patients get these antipsychotics in the hands of very good doctors at extremely good medical centers. And so that means, translation, worldwide that millions of people are getting these drugs to treat their delirium.

HARRIS: But that medical practice was based on tradition, not solid science. So Dr. Ely and his colleagues ran a formal clinical trial involving more than 500 patients to see if the drugs actually worked. Patients with delirium were split into three groups. One group got the most powerful antipsychotics. A second group got what's called an atypical antipsychotic - ziprasidone. A third group got placebo. Ely says the drugs made absolutely no difference.

ELY: Neither group had any detectable reduction in delirium, coma. 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 one way or the other. And there's really 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.

HARRIS: Yes, the drugs can calm patients down, but they don't treat delirium.

JULI BARR: This is huge.

HARRIS: Dr. Juli Barr at Stanford University has helped craft guidelines for appropriate drug use in the intensive care unit.

BARR: Providers really need to think differently about managing delirium in their patients in the ICU, that a pill or an injection's really not a magic bullet for this devastating illness.

HARRIS: Both she and Ely advocate for a more holistic approach to treating delirium by getting patients off drugs and off breathing machines as soon as possible and getting them up and about as soon as they're able. Richard Harris, NPR News. Transcript provided by NPR, Copyright NPR.