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Optimal Assessment and Management of Agitation in Alzheimer’s Disease

Optimal Assessment and Management of Agitation in Alzheimer’s Disease Posted By:
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Agitation in Alzheimer’s disease (AAD) can be a serious safety risk for patients and caregivers. Aside from dramatically affecting the health and stress levels of caregivers, family, and significant others, AAD is responsible for patients experiencing increased rates of emergency department visits and hospitalizations and puts them at higher risk of long-term care placement.

One of the main challenges in AAD management is reaching an accurate diagnosis. How can a busy healthcare professional (HCP) identify and quantify AAD? Let’s discuss some options, starting with the Neuropsychiatric Inventory (NPI). The NPI is an objective, well-studied instrument that scores neuropsychiatric symptoms common in dementia. It assesses the presence of concerning or challenging behaviors, as well as their frequency, their severity, and resulting caregiver stress.

A second tool used to diagnose AAD is the International Psychogeriatric Association (IPA) consensus definition for agitation in cognitive disorders (including Alzheimer’s disease [AD]), which was updated in March 2023. The IPA definition includes 4 criteria.

  1. Diagnosis of cognitive impairment or dementia syndrome (eg, AD).
  2. Patient exhibits at least 1 behavior associated with emotional distress (excessive motor activity, verbal aggression, physical aggression) for a minimum of 2 weeks or the behavior represents a dramatic change from baseline behaviors.
  3. The agitation behavior(s) must be severe enough to cause excess distress or disability and affect interpersonal relationships, social functioning, or activities of daily living.
  4. Agitation is not solely attributable to another cause (eg, other psychiatric disorder, care condition, substance effect, other medical condition).

If IPA criteria are met, nonpharmacologic approaches are the first step for AAD management. If the behaviors present a safety/danger risk to the patient or others, however, a pharmacologic approach may be required as the initial intervention.

Three colleagues and I designed and authored a decision tree on AAD for HCPs as a 2022 project of the Gerontological Society of America (GSA). Our goal was to assist HCPs in navigating the assessment and treatment of AAD at home or in care facility settings. It includes guidance on assessing and optimally treating AAD with pharmacologic and/or nonpharmacologic measures.

Like the IPA criteria, the GSA AAD decision tree requires ruling out and treating a reversible delirium superimposed on AD (eg, urinary tract infection, dehydration, metabolic changes) or agitation and psychosis due to depression or other chronic psychiatric illnesses before progressing to AAD management.

Over the course of my career as a long-term care (LTC) dementia consultant, I have seen innumerable situations in which highly anticholinergic agents or benzodiazepines/hypnotics (ironically and unfortunately used for AAD) cause or worsen agitation behaviors. This frequently results in the prescriber adding a second medication to treat the adverse event of the initial medication, which may have been listed under the Beers Criteria for Potentially Inappropriate Medication Use in Older Adults in the first place.

Nonpharmacologic strategies are next on the decision tree. The options here are robust. A 2015 systematic review by de Oliveira and colleagues analyzed 10 years of research on nonpharmacologic strategies for behavioral symptoms of dementia and found that the most effective interventions for agitation included tailored activity programs, live music or group music activities, aromatherapy using lavender or Melissa oil/lemon balm, combination of aromatherapy and acupressure, therapeutic touch, and combination activities (music, art, and exercise).

Further evidence for nonpharmacologic strategies in AAD includes a 2020 meta-analysis of 65 randomized, controlled trials by Leng and colleagues. This meta-analysis concluded that massage therapy, animal-assisted intervention, and personally tailored interventions were associated with substantial agitation reduction vs other nonpharmacologic interventions.

Brexpiprazole is the first and only FDA-approved medication for AAD. Other atypical antipsychotics are also often used off label for AAD; unfortunately, older typical antipsychotics, which have a higher adverse event burden, are still sometimes used, as well. In 20 years of clinical practice providing pharmacologic and nonpharmacologic interventions for dementia in LTC, I have had success ameliorating levels of AAD (after treating delirium and depression) by using FDA-approved cognitive enhancers for AD (eg, cholinesterase inhibitors [ChEIs] initially, then adding memantine). Combination therapy (ChEI plus memantine) has helped me delay onset and decrease overall severity of AAD and related behaviors in the majority of my LTC and memory care unit residents. These strategies are outlined below and were presented at the GSA 2022 Annual Scientific Meeting.

  1. Initiate at the lowest dose, titrate as directed, and maximize ChEI of choice (start early and continue through late stages of AD).
  2. Add memantine to fully titrated ChEI of choice, starting at beginning of moderate stage of AD and titrating as directed to maximum dose.
  3. If donepezil is selected instead of rivastigmine and galantamine, it can be prescribed as a combination capsule with memantine when/after the donepezil dose of 10 mg is achieved.
  4. Continue anti-AD medications into the late to end/terminal stages of AD.
  5. Avoid benzodiazepines, hypnotics, and anticholinergic medications.
  6. Consider an antidepressant if anxiety or depression manifests as or with behavioral and psychological symptoms of dementia. Use one with a low anticholinergic load and favorable geriatric profile.

Often, antipsychotic medications are considered to address AAD. In fact, as a novice gerontological nurse practitioner 40 years ago, typical antipsychotics (eg, haloperidol, thiothixene, chlorpromazine) were routine practice for managing AAD. I cringe now to think about the regular and acceptable practices of using wrist and hand mitt restraints, having residents sit in geri-chairs (contractures and immobility) all day, and prescribing high-potency neuroleptics (with significant adverse events, including tardive dyskinesia and parkinsonism).

Atypical antipsychotics were issued a black box warning in 2005, as were typical antipsychotics in 2008, for use in older patients with dementia. However, FDA-approved brexpiprazole and other atypical agents do have a place in AAD management. As our GSA decision tree concluded (per a 2016 description by Reus and colleagues): “Antipsychotic medications should be used for the treatment of agitation in AD only when symptoms are severe or cause significant distress to the patient and/or pose danger to the patient or others in the environment. Before nonemergency treatment with an antipsychotic is initiated in patients with dementia, potential risks and benefits should be assessed by the clinician and discussed with the patient (if clinically feasible), as well as with the patient’s surrogate decision maker (if relevant) with input from family or others involved.”

I have been waiting a very long time for more palatable options to help patients with AAD. The approval of brexpiprazole (a third-generation antipsychotic), as well as research on innovative/alternative neurotransmitter/receptor mechanisms, holds promise and potential.

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Filed under: Neurology , Psychiatry , NPs & PAs

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