Commentary: When Less Is More


Michael Keys, MD

In “Scheduled Low-Dose Risperidone for Agitation in Elderly Patients” (page 40), Nguyen and colleagues discuss important fundamentals in the management of agitation and psychotic symptoms in patients with delirium, dementia, or both.1 They report two cases that present a familiar scenario to most consulting psychiatrists: An agitated, frail, elderly patient with complex and multifactorial underlying medical issues is given an unheard of amount of haloperidol and lorazepam for recurring agitation, resulting in a worsening of symptoms. The psychiatrist is consulted, and with a working diagnosis of delirium, he or she shifts treatment to a relatively low dose of a routine, high-potency antipsychotic, resulting in a marked improvement in the patient’s symptoms over the next 24 hours. Is this improvement the result of the addition of a routine antipsychotic, or is it attributable to an overall improvement in the patient’s medical condition? One can never be certain, and Nguyen and colleagues are unable to satisfactorily answer this question. However, the authors do ask a highly pertinent question, namely, what is the minimal effective dosing when using antipsychotics in the management of delirium? Certainly, there has been progress in better recognizing delirium in a variety of clinical settings and in defining subtypes of delirium, identifying vulnerable patients (such as those with known dementia or a history of delirium), developing protocols to promote best management that address both environmental factors and bedside care, and developing preventive strategies in vulnerable patients. While the pathophysiology of delirium is complex and varied, there is now enhanced understanding of a number of contributory processes, including underlying cholinergic and dopaminergic dysregulation, which provides insights on why the use of dopaminergic antagonists may have a significant clinical benefit. It has been almost 12 years since the American Psychiatric Association released its practice guideline for the treatment of patients with delirium, which advocate using high-potency antipsychotics, specifically haloperidol, for managing agitation and prominent positive psychotic symptoms.2 Since then, we have had the U.S. Food and Drug Administration warn of an increased mortality risk with the use of antipsychotic medications in patients with advanced dementia, which is a population at risk for concomitant delirium, as demonstrated by the cases reported by Nguyen and colleagues. Yet, antipsychotic medications continue to be the mainstay of pharmacologic intervention for patients with delirium with core features of agitation, hallucinations, and delusions. While there is significant evidence both clinically and in published reports to support the use of antipsychotics in patients with delirium, highquality, blinded, randomized, controlled studies to inform our knowledge on the safety, benefits, and clinical use of antipsychotics in this population, as well as in those with underlying dementia and superimposed delirium, are severely lacking.3,4 The cases presented by Nguyen and colleagues highlight four principles that serve as helpful clinical guides in managing, and, perhaps, give balance to, the clinical use of antipsychotics in frail elderly patients with delirium. 1. Use of routine and timed antipsychotic medications may be more effective than use of as-needed medications in the emergence of signs and symptoms of delirium.

2. Antipsychotics should have a limited timed duration of use over a period of days. These regimens should resemble those of antibiotics, with limited duration, so that patients are not discharged with unneeded continuous prescribed antipsychotics.

3. Relatively ultra-low doses of antipsychotics given routinely may be effective in reducing symptoms of agitation and psychosis, while also reducing the risk of adverse events in vulnerable populations.

4. Longer-term follow-up is essential. It is estimated that 50% to 80% of patients with an index episode of delirium will continue to show symptomatic changes at 1 month, and this may be much longer for many patients.2 Informed follow-up management, especially for patients transferred from one setting to another, is key to consistent care.

While case studies can shine light on potential avenues of research, they do not offer definitive answers. We still have much to learn about the specifics of using antipsychotic medications in elderly patients with delirium. For example, how safe are these medications? What is the proper dosing, route of delivery, frequency, and duration of use? Are some agents better than others? Are these agents useful in various subtypes, such as hypoactive states versus more agitated presentations? Are these agents useful as prophylaxis in identified populations, such as patients with a history of postoperative delirium who are scheduled for surgery? Are there alternative pharmacologic treatments? Although there have been significant efforts at better designed interventional studies in patients with delirium, which would help answer these questions, this is a difficult population to study due to heterogeneity, complex medical issues, high morbidity and mortality rates, and difficulty in obtaining informed consent. There is certainly a need for more blinded, randomized, placebo-controlled studies that would better delineate both the safety issues and clinical benefits of antipsychotics and other pharmacologic and nonpharmacologic strategies in managing delirium. The ultimate goal in managing delirium remains identifying vulnerable patients and implementing effective strategies to prevent and mitigate cognitive and behavioral disruption at the earliest point in time. Yes, less is more. The author reports no relevant financial relationships. Dr. Keys is director, Senior Program, Linder Center of Hope, Mason, OH, and associate professor of clinical psychiatry, University of Cincinnati College of Medicine, Cincinnati, OH. References 1. Nguyen ML, Patel SB, Shapiro MA. Scheduled low-dose risperidone for agitation in elderly patients. Annals of Long-Term Care: Clinical Care and Aging. 2011;19(2):40-43.

2. American Psychiatric Association. Practice guideline for the treatment of patients with delirium. Am J Psychiatry. 1999;156(5 suppl):1-20.

3. Seitz DP, Gill SS, van Zyl LT. Antipsychotics in the treatment of delirium: a systematic review. J Clin Psychiatry. 2007;68(1):11-21.

4. Bourne RS, Tahir TA, Borthwick M, Sampson EL. Drug treatment of delirium: past, present and future. J Psychosom Res. 2008;65(3):273-282.

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