Delirium is a negative consequence of illness; it is upsetting for patients and families and costly to the healthcare system. Since medications are easy to give to patients, it is tempting to use a drug to help resolve delirium and its bad outcomes – however, the strongest evidence to prevent and successfully treat delirium points to non-pharmacologic approaches. These include getting patients out of bed and moving as soon as possible, reorienting them regularly, avoiding deeply sedating them and offering sleep aids like earplugs and eye masks to promote adequate rest.. These strategies should be incorporated into the care delivered by every medical and surgical service.
While research shows that up to one third of delirious episodes can be prevented with non-pharmacologic management, we still want and need to find better ways to prevent and treat the remainder of delirium episodes that occur. Furthermore, it is thought that an imbalance of neurotransmitters (the chemicals released in the brain) and several types of disease processes (such as inflammation from infections) contribute to the clinical picture of delirium. For these reasons, clinicians and researchers have turned to medications in hopes of finding something that helps.
This post briefly reviews what we know about pharmacologic or medication treatment approaches. Note that there are no FDA approved medications for the treatment of delirium.
Studies have examined the use of antipsychotic medications (most often haloperidol) for preventing or shortening the course of delirium. The studies that are available are generally small in size, study different types of patients, and measure outcomes in different ways. When the findings are examined as a group, we do not see clear evidence that using antipsychotics to treat delirium changes the number of people who die, the duration of delirium, the severity of delirium, time spent in the Intensive Care Unit (ICU) or time to breathing on one’s own in the ICU. With all antipsychotics having the potential to cause serious side effects, they should not be administered unless the potential benefit outweighs any safety concerns.
Antipsychotics also do not seem to prevent the occurrence of delirium when given before surgery. However, one small but well-conducted study found that giving a newer antipsychotic drug, called risperidone, to people with very mild symptoms of delirium in the recovery room after surgery, decreased delirium in the recovery period. This study needs to be repeated in a larger group of patients before we can recommend such an approach for everyone.
None of the studies referred to above address whether the use of antipsychotics was helpful in making the patient feel better. Delirium sometimes causes hallucinations and delusions and often results in anxiety and fear. Antipsychotics are effective treatments of such symptoms when they accompany major illness. Therefore, it may be justifiable to treat these symptoms during delirium with low doses of medicationsfor brief periods of time, even if we are not convinced that the antipsychotic decreases the length of the delirium episode itself. More research is needed to study this question.
Melatonin and Melatonin Agonist Medications
Melatonin is a naturally occurring hormone in our bodies that regulates the diurnal rhythm. Delirium researchers have been interested in melatonin because delirium frequently disrupts the day-night pattern. Early studies suggested that melatonin might prevent delirium from occurring, but recently a carefully conducted experiment in The Netherlands did not demonstrate any significant benefit after melatonin was used in elderly patients who had been hospitalized for a hip fracture.
Ramelteon is a melatonin receptor-stimulating agent that is marketed in the US as a sleep medicine. A recent study reported that delirium in older hospitalized patients in Japan could be prevented with ramelteon. We need more research to understand if melatonin or associated medications can be useful in preventing or treating delirium.
This class of medications was thought to hold some promise in treating delirium, but a well-designed treatment trial was discontinued because of concern that the acetylcholinesterase inhibitor might be causing harm to the participants in the study. This line of research has been stopped for now.
Medications from the benzodiazepine class, such as diazepam and lorazepam, are not found to help patients with delirium and may result in making the delirium worse. One exception is possibly the treatment of delirium that is caused by alcohol or benzodiazepine withdrawal. Avoid using benzodiazepines in the agitated patient who has no recent history of alcohol or benzodiazepine dependence and consider the use of dexmedetomidine instead for a patient in the ICU.
Karin J. Neufeld, MD, MPH
Clinical Director –Bayview Psychiatry
Department of Psychiatry and Behavioral Sciences
Johns Hopkins University School of Medicine
American Geriatrics Society Expert Panel on Postoperative Delirium in Older Adults. (2015). American geriatrics society abstracted clinical practice guideline for postoperative delirium in older adults. Journal of the American Geriatrics Society, 63(1), 142-150. doi:10.1111/jgs.13281 [doi]
Barr, J., Fraser, G. L., Puntillo, K., Ely, E. W., Gelinas, C., Dasta, J. F. American College of Critical Care Medicine. (2013). Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Critical Care Medicine, 41(1), 263-306. doi:10.1097/CCM.0b013e3182783b72 [doi]
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