Risks of Antipsychotics for Treatment of Delirium May Outweigh Benefits, Review Finds

There may be no benefits to treating hospitalized patients experiencing delirium with antipsychotics, suggests a review published this week in the Annals of Internal Medicine.
Delirium—which is characterized by sudden changes in attention, decreased awareness, and cognitive impairment—is known to be associated with worse patient outcomes, wrote Roozbeh Nikooie, M.D., of Johns Hopkins University School of Medicine and colleagues. Such outcomes include increased length of stay in the hospital, long-term cognitive impairment, and mortality.
Although the first-generation antipsychotic haloperidol and second-generation antipsychotics are commonly used to treat hospitalized patients for delirium, the benefits and risks of this treatment strategy remain unclear, the authors wrote. They conducted a systematic review of 26 studies that compared outcomes of hospitalized adults with delirium who were treated with haloperidol, a second-generation antipsychotic (such as risperidone, quetiapine, or olanzapine), or placebo. The studies included 16 randomized, controlled trials involving 1,768 participants and 10 observational studies involving 3,839 participants.
The authors found that patients had similar delirium duration, sedation status, hospital length of stay, and mortality regardless of whether they received an antipsychotic or placebo. (There was insufficient evidence regarding the effect of these medications on cognitive function or delirium severity.) When comparing patients who received haloperidol with those who received second-generation antipsychotics, the authors found that the groups appeared similar in terms of their cognitive function, delirium severity, sedation status, hospital length of stay, and mortality.
While there was “little evidence of harm for haloperidol and second-generation antipsychotics with short-term use for treating delirium in adult inpatients …, potentially harmful cardiac effects tended to occur more frequently with use of antipsychotics, particularly prolongation of the QT interval with second-generation antipsychotics versus placebo or haloperidol,” the authors noted.
Nikooie and colleagues highlighted several limitations of the review: “Some large studies in this review were conducted in critically ill patients, which may affect generalizability of the findings. Moreover, most RCTs [randomized, controlled trials] excluded patients with underlying neurologic or cardiovascular issues, which can potentially underestimate the harms in routine clinical practice.” Nonetheless, they concluded, “Current evidence does not support routine use of haloperidol or second-generation antipsychotics to treat delirium in adult inpatients.”
For related information, see the American Journal of Psychiatry article “The American Psychiatric Association Practice Guideline on the Use of Antipsychotics to Treat Agitation or Psychosis in Patients With Dementia.”

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