Treating Dementia-Associated Behavioral Disturbances and Delirium

By Luke D. Kim, MD, FACP, CMD, and Ardeshir Z. Hashmi, MD, FACP

Behavioral and psychiatric symptoms often accompany dementia, but no drugs have yet been approved by the U.S. Food and Drug Administration (FDA) to address them in this population. Nonpharmacologic interventions are recommended as first-line therapy.

Antipsychotics are not recommended

Antipsychotics are often prescribed, although they are associated with metabolic syndrome and increased risks of stroke and death. The FDA has issued black box warnings against using antipsychotics for behavioral management in patients with dementia. Further, the American Geriatrics Society and the American Psychiatric Association do not endorse using them as initial therapy for behavioral and psychological symptoms of dementia.

The Centers for Medicare and Medicaid Services partnered with nursing homes to improve the quality of care for patients with dementia, with results measured as the rate of prescribing antipsychotic medications. Although the use of psychotropic medications declined after initiating the partnership, the use of mood stabilizers increased, possibly as a substitute for antipsychotics.

Dextromethorphan-quinidine use is up, despite modest evidence of benefit

A consumer news report in 2017 stated that the use of dextromethorphan-quinidine in long-term care facilities increased by nearly 400 percent between 2012 and 2016.

Evidence for its benefits comes from a 10-week, phase 2, randomized controlled trial conducted at 42 U.S. study sites with 194 patients with probable Alzheimer disease. Compared with the placebo group, the active treatment group had mildly reduced agitation but an increased risk of falls, dizziness and diarrhea. However, rates of adverse effects were low, and the authors concluded that treatment was generally well-tolerated.

Pimavanserin: No long-term benefit for psychosis

In a phase 2, randomized, double-blind, placebo-controlled trial in 181 patients with possible or probable Alzheimer disease and psychotic symptoms, pimavanserin was associated with improved symptoms as measured by the Neuropsychiatric Inventory–Nursing Home Version psychosis score at six weeks, but no difference was found compared with placebo at 12 weeks. The treatment group had more adverse events, including agitation, aggression, peripheral edema, anxiety and symptoms of dementia, although the differences were not statistically significant.

Delirium: Avoid antipsychotics

Delirium is common in hospitalized older adults, especially those who have baseline cognitive or functional impairment and are exposed to precipitating factors such as treatment with anticholinergic or narcotic medications, infection, surgery or admission to an intensive care unit.

In a prospective study of 152 hospitalized patients with delirium, those who either did not recover from delirium or had only partially recovered at discharge were more likely to visit the emergency department, be rehospitalized or die during the subsequent three months than those who had fully recovered from delirium at discharge.

A randomized trial in 377 patients in Taiwan evaluated the use of a modified Hospital Elder Life Program, consisting of three protocols focused on orienting communication, oral and nutritional assistance, and early mobilization. Patients were at least 65 years old and undergoing elective abdominal surgery with expected length of hospital stay longer than six days. The program, administered daily during hospitalization, significantly lowered postoperative delirium by 56 percent and hospital stay by two days compared with usual care.

In a multicenter randomized, double-blind, placebo-controlled trial, van den Boogaard et al studied prophylactic intravenous haloperidol in nearly 1,800 critically ill patients at high risk of delirium. Haloperidol did not improve survival at 28 days compared with placebo. For secondary outcomes, including delirium incidence, delirium-free and coma-free days, duration of mechanical ventilation and hospital and intensive care department length of stay, treatment was not found to differ statistically from placebo.

A double-blind, parallel-arm, dose-titrated randomized trial, conducted at 11 Australian hospices or hospitals with palliative care services, administered oral risperidone, haloperidol or placebo to 247 patients with life-limiting illness and delirium. Both treatment groups had higher delirium symptom scores than the placebo group.

In addition, a systematic review and meta-analysis of 19 studies found no benefit of antipsychotic medications for preventing or treating delirium in hospitalized adults.

This abridged article originally appeared in Cleveland Clinic Journal of Medicine.

Dr. Kim is staff in the Center for Geriatric Medicine. Dr. Hashmi directs the Center for Geriatric Medicine.