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No Benefit to Treating Delirium With Antipsychotics or Haloperidol

September 04, 2019

By Marilynn Larkin

NEW YORK—Current evidence does not support the use of second-generation antipsychotics or haloperidol to treat or prevent delirium in adult inpatients, two systematic reviews reveal.

"For clinicians currently prescribing antipsychotic medications as a general treatment strategy for delirium, or using haloperidol to prevent delirium, this review should be considered practice changing," Dr. Karin Neufeld of Johns Hopkins University School of Medicine in Baltimore, told Reuters Health by email. "There is little to no evidence of any benefit when compared to placebo."

"Furthermore, antipsychotic agents have many potential risks including the possibility of their inappropriate continuation long after the delirium has resolved, and should not be started routinely as a general treatment for delirium," she said. "Similarly, haloperidol should not be used routinely to prevent the new onset of delirium."

She added that the findings are consistent with guidelines from the Society of Critical Care Medicine ( and the American Geriatrics Society (

Dr. Neufeld and colleagues searched the literature and identified 16 randomized controlled trial and 10 observational studies of hospitalized adults with delirium.

As reported online September 2 in Annals of Internal Medicine, there was no difference in sedation status between haloperidol and second-generation antipsychotics versus placebo; strength of evidence (SOE) was low to moderate. Nor were there differences in delirium duration, hospital length of stay (moderate SOE), or mortality.

Further, there was no difference in delirium severity (moderate SOE) and cognitive functioning (low SOE) for haloperidol versus second-generation antipsychotics, and insufficient or no evidence for antipsychotics versus placebo.

Direct comparisons of different second-generation antipsychotics demonstrated no difference in mortality and insufficient or no evidence for multiple other clinical outcomes.

There was little evidence of neurologic harms associated with short-term use of antipsychotics in these patients, but potentially harmful cardiac effects tended to occur more frequently.

Similarly, in a separate systematic review in the same issue, Dr. Neufeld and colleagues found that current evidence does not support the routine use of second-generation antipsychotics or haloperidol for delirium prevention, although some evidence suggests a possible benefit of second-generation antipsychotics in postoperative settings.

Dr. Neufeld said, "Better delirium prevention and treatment must start with systematic screening, particularly in high-risk areas such as an intensive care unit, and in high-risk patients - i.e., over age 65. All medical disciplines should be aware of the syndrome, have a high index of suspicion in high-risk cases, and should be able to evaluate the patient for the condition."

Delirium assessment tools are available at

"Delirium screen-positive patients require further evaluation and treatment of the underlying cause or causes," she continued. "Rectifying the etiology of the delirium is the most important first step in treating a patient with delirium."

"Non-pharmacologic strategies are the most effective approaches for preventing and decreasing delirium duration and should be employed as a standard of care," she stressed. Such interventions include: reducing exposure to deliriogenic medications in patients over 65; early mobility, physical rehabilitation and cognitive stimulation; sleep/wake cycle hygiene; frequent re-orientation, and accessibility to eye glasses and hearing aides; adequate hydration; and attention to bowel and bladder function."

Dr. Edward Marcantonio of Beth Israel Deaconess Medical Center in Boston, author of a related editorial, commented by email, "The findings support stopping the practice of using of antipsychotics for treatment of delirium. There might still be small groups of affected individuals...for whom non-pharmacological interventions are insufficient, who might benefit from short-term use of these drugs targeted at the behavior, not at delirium.

"Defining these populations, and how to administer these drugs in this setting, is still open for future research," he said.

"We need to move away from the idea that delirium, a complex multifactorial syndrome, can be treated with a single drug or even a single class of drug," he told Reuters Health.

Like Dr. Neufeld, he noted, "Once delirium is identified, it is essential to treat the underlying conditions that cause the delirium. For instance, if delirium is caused by a urinary tract infection, then the treatment is antibiotics; if caused by congestive heart failure, then diuretics; if caused by alcohol/sedative withdrawal, then benzodiazepines; if caused by a new sleeping pill, then by stopping the sleeping pill, etc."

"In many cases, multiple interventions are needed," he said.

"While delirious, patients are at very high risk for complications - e.g., falls, pressure ulcers," he added. "So, a proactive program to prevent these complications is needed. We (also) know that delirium is associated with prolonged functional impairment, so a program to restore function - both cognitive and physical - should be implemented."

SOURCE:, and

Ann Intern Med 2019.

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