Management of agitation in dementia: Good practice or malpractice?

MANAGEMENT OF AGITATION IN DEMENTIA: GOOD PRACTICE OR MALPRACTICE?
Elias Ghossoub, MD, MSc. (1) and Rita Khoury, MD (2)
(1) Department of Psychiatry, American University of Beirut, Beirut, Lebanon
(2) Department of Psychiatry and Clinical Psychology, Saint Georges Hospital University Medical Center, Faculty of Medicine, University of Balamand, Beirut, Lebanon

Key Highlights:

• Non-Pharmacological approaches such as music therapy and caregiver education should always be used as first line treatment for agitation in patients with dementia.
• When non-pharmacological approaches fail, pharmacotherapy is needed.
• Psychotropics currently used off-label have modest efficacy with some side effects, raising liability issues among practitioners.
• Documentation remains the most crucial measure for physicians to reduce their risk of malpractice liability.
• Physicians should use the lowest effective dose, while periodically assessing efficacy, safety, and the clinical indication.

Introduction

Agitation is one of the most distressing behavioral and psychological symptoms of dementia (BPSD), leading to disability, long-term care placement and poor quality of life among both patients and caregivers (Okura et al. 2011). The International Psychogeriatric Association recently developed a provisional definition for agitation in cognitive disorders, which is currently being used in clinical research; it is presented in table 1 (Cummings et al. 2015).

Management of agitation is challenging in the absence of Food and Drug Administration (FDA)-approved pharmacological options. The first-line approach is non-pharmacological and involves caregiver education and environmental adaptations (Kales et al. BMJ 2015). A systematic review of randomized controlled trials focused on non-pharmacological strategies for agitation in older adults with Alzheimer’s disease, which showed that music therapy, notably individualized and interactive music may be an optimal intervention for moderate to severe agitation. Other strategies include aromatherapy, bright light therapy, therapeutic touch, etc. (Millán-Calenti et al. 2016). When non-pharmacological approaches are insufficient, judicious use of pharmacological treatment is recommended. Unfortunately, psychotropics used off-label have limited efficacy and some safety concerns in older adults with dementia, raising liability concerns among physicians.

A fine balance between efficacy and safety

Antidepressants have been investigated for agitation in Alzheimer’s disease: The Citalopram for Agitation in Alzheimer Disease (CitAD) study found citalopram reduced agitation in this population, even with no comorbid depression. It was however associated with worsening of cognition and a prolonged QTc interval, at the 30 mg daily dose used in the trial, which is greater than the 20 mg maximum dose approved by the FDA in older adults (Porsteinsson et al. 2014). Trazodone is a calming antidepressant used at doses of 50-300 mg for mild agitation and irritability (López-Pousa et al. 2008). It is considered a safe strategy (with some risk of dizziness and orthostatic hypotension), but efficacy was not demonstrated however in moderate to severe agitation (Martinon-Torres et al. 2004).

Antipsychotics such as risperidone and olanzapine are prescribed for severe agitation, especially in cases with underlying psychosis. Both risperidone and olanzapine were shown to be superior to quetiapine or placebo in the treatment of agitation and psychosis in Alzheimer’s disease (Sultzer et al. 2008). Adverse events include extra-pyramidal symptoms, abnormal gait, worsening cognition, increased risk of cerebrovascular events and mortality (Schneider et al. 2006).  All antipsychotics carry an FDA black-box warning regarding increased risk of death in older adults with dementia (Yan, 2008). Given their liability, the American Psychiatric Association (APA) recommends assessing their benefits versus risks on a case-by-case basis. The APA also advises discontinuing the drug in the absence of a clinically significant response after a 4-week trial. If a patient responded to an antipsychotic, the physician should always attempt to taper the dose and withdraw the drug within 4 months of initiation, unless the patient experienced recurrence of symptoms with prior attempts at tapering (Reus et al. 2016). In all case scenarios, documentation in the patient’s record is a required.  

In 2012, the Center for Medicare and Medicaid Services (CMS) launched a national partnership to improve dementia care in nursing homes, with an initial goal of reducing inappropriate antipsychotic medication use. Indeed, according to recent CMS reports, there has been about a 40% decrease in antipsychotic prescriptions, which reduced the prevalence in U.S. nursing homes to 14.3% in 2019 (National Partnership to Improve Dementia Care in Nursing Homes, October 2019). Following this initiative, the use of antiepileptics/mood stabilizers rapidly increased as a substitute for antipsychotics, although possibly with a poorer risk/benefit ratio (Maust et al. 2018).

There is less evidence on the efficacy of antiepileptics for agitation: when carbamazepine is used, physicians should be vigilant to the potential for drug-drug interaction as it is an inducer of the hepatic CYP3A4 (Olin et al. 2001). Divalproex is associated with an increased rate of adverse events such as somnolence, nausea, vomiting, and thrombocytopenia in frail older adults with dementia (Baillon et al. 2018). Anxiolytics such as lorazepam are being used on an as needed basis due to their limited efficacy for agitation; they are associated with increased risk of falls and confusion (Defrancesco et al. 2015).

What about the benefits and risks of physical restraints?

Physical restraint can be defined as any device, material or equipment attached to or near a person’s body, which cannot be controlled or removed by the person,  and which deliberately prevents or is deliberately intended to prevent a person’s free body movement. Examples include vests, straps/belts, limb ties, wheelchair bars / brakes, chairs that tip backwards, tightly tucked sheets, and bedside rails. The reported use of physical restraints in nursing homes varies from 4% to 85%, and the risks include bruises, decubitus ulcers, respiratory complications, urinary incontinence, constipation, malnutrition, increasing dependence for activities of daily living, impaired muscle strength and balance, cardiovascular deconditioning, increased agitation, or increased risk of mortality due to strangulation or head trauma related to attempts at escape (Gastmans et al. 2006).

Physical restraint should only be used as a last resort, after considering all possible alternatives, and the prescription needs to be for the shortest period of time, using the least restrictive material, with careful supervision by staff. The patient’s preference should always be considered, and the decision should involve patient and caregivers early in the process. In these cases, clear documentation of careful decision-making is necessary in the patient’s record (Scheepmans et al. 2020).

How to Reduce the Risk of Malpractice Liability?

Around a third of paid malpractice claims involving older adults were related to medication/treatment (Mello and Kachala, 2016). Documentation remains the most crucial measure for physicians to reduce their risk of malpractice liability (Melonas and Cash, 2009; Cowles, 2015). Additionally, physicians should establish good rapport with their patients and, when appropriate, their patients’ families (Melonas and Cash, 2009; Cowles, 2015). Non-pharmacological interventions should be prioritized whenever possible (Cowles, 2015). When pharmacological agents are clinically indicated, treating physicians should obtain informed consent from the patient and/or the patient’s legal representative to start the recommended agent (Melonas and Cash, 2009; Cowles, 2015). Physicians then should use the lowest effective dose of medication while periodically assessing efficacy, safety, and the clinical indication (Cowles, 2015).

Table 1. Consensus Provisional Definition of Agitation in Cognitive Disorders

References

• Baillon SF, Narayana U, Luxenberg JS, et al. Valproate preparations for agitation in dementia. Cochrane Database Syst Rev. 2018;10(10):CD003945-CD003945.
• Cowles C. Risky Business: Avoiding Liability for Prescribing Antipsychotics. Caring for the Ages, 2015;16(7):19.
• Cummings J, Mintzer J, Brodaty H, et al. Agitation in cognitive disorders: International Psychogeriatric Association provisional consensus clinical and research definition. Int Psychogeriatr. 2015;27(1):7-17.
• Defrancesco M, Marksteiner J, Fleischhacker WW, et al. Use of Benzodiazepines in Alzheimer's Disease: A Systematic Review of Literature. Int J Neuropsychopharmacol. 2015;18(10):pyv055-pyv055.
• Gastmans C, Milisen K. Use of physical restraint in nursing homes: clinical-ethical considerations. J Med Ethics. 2006;32(3):148-152.
• Kales HC, Gitlin LN, Lyketsos CG, et al. Management of neuropsychiatric symptoms of dementia in clinical settings: recommendations from a multidisciplinary expert panel. J Am Geriatr Soc. 2014 Apr;62(4):762-9.
• López-Pousa S, Garre-Olmo J, Vilalta-Franch J, Turon-Estrada A, Pericot-Nierga I. Trazodone for Alzheimer's disease: a naturalistic follow-up study. Arch Gerontol Geriatr. 2008;47(2):207-15.
• Martinon-Torres G, Fioravanti M, Grimley EJ. Trazodone for agitation in dementia. Cochrane Database Syst Rev. 2004;(4):CD004990.
• Maust DT, Kim HM, Chiang C, et al. Association of the Centers for Medicare & Medicaid Services' National Partnership to Improve Dementia Care With the Use of Antipsychotics and Other Psychotropics in Long-term Care in the United States From 2009 to 2014. JAMA Intern Med. 2018;178(5):640-647.
• Mello MM, and Kachalia A. Medical Malpractice: Evidence on Reform Alternatives and Claims Involving Elderly Patients. 2016. Retrieved from: http://www.medpac.gov/docs/default-source/reports/dec16_medicalmalpractice_medpac_contractor.pdf
• Melonas JM, and Cash CD. Identifying and reducing professional liability when treating older adults: actions you can take to decrease risks while increasing patient safety. Psychiatric Times. 2009;26(1):30.
• Millán-Calenti JC, Lorenzo-López L, Alonso-Búa B, et al. Optimal nonpharmacological management of agitation in Alzheimer's disease: challenges and solutions. Clin Interv Aging. 2016;11:175-184.
• National Partnership to Improve Dementia Care in Nursing Homes: Antipsychotic Medication Use Data Report. 2019. Retrieved from https://www.cms.gov/files/document/antipsychotic-medication-use-data-report-updated-01242020.pdf.
• Okura T, Plassman BL, Steffens DC, et al. Neuropsychiatric symptoms and the risk of institutionalization and death: the aging, demographics, and memory study. J Am Geriatr Soc. 2011;59(3):473-481.
• Olin JT, Fox LS, Pawluczyk S, et al. A pilot randomized trial of carbamazepine for behavioral symptoms in treatment-resistant outpatients with Alzheimer disease. Am J Geriatr Psychiatry. 2001;9(4):400-5.
• Porsteinsson AP, Drye LT, Pollock BG, et al. Effect of citalopram on agitation in Alzheimer disease: the CitAD randomized clinical trial. JAMA. 2014;311(7):682-91.
• Reus VI, Fochtmann LJ, Eyler AE, et al. The American Psychiatric Association Practice Guideline on the Use of Antipsychotics to Treat Agitation or Psychosis in Patients With Dementia. Am J Psychiatry. 2016;173(5):543-546.
• Scheepmans K, Dierckx de Casterlé B, Paquay L, et al. Reducing physical restraints by older adults in home care: development of an evidence-based guideline. BMC Geriatr 20, 169 (2020). https://doi.org/10.1186/s12877-020-1499-y
• Schneider LS, Dagerman K, Insel PS. Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomized, placebo-controlled trials. Am J Geriatr Psychiatry. 2006 Mar;14(3):191-210.
• Sultzer DL, Davis SM, Tariot PN, et al. Clinical symptom responses to atypical antipsychotic medications in Alzheimer's disease: phase 1 outcomes from the CATIE-AD effectiveness trial. Am J Psychiatry. 2008;165(7):844-854.
• Yan J. FDA Extends Black-Box Warning to All Antipsychotics. Psychiatric News. 2008. Retrieved from: https://psychnews.psychiatryonline.org/doi/full/10.1176/pn.43.14.0001

Dr. Rita Khoury is an assistant professor of clinical psychiatry at Balamand University, Beirut Lebanon. She practices adult and geriatric psychiatry at Saint George Hospital University Medical Center, Lebanon. Her research interests include the pathophysiology and treatment of neurocognitive disorders (dementias).

Excerpted from the IPA Bulletin, Volume 37, Number 4.