What Are Effective Pharmacological and Nonpharmacological Treatments for Delirium?

Introduction and Scope of the Problem

Delirium is a neuropsychiatric disorder characterized by an acute change in consciousness, attention, and cognition, with a tendency to fluctuate through the course of a day. It is defined in the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) by the following characteristics: (1) a disturbance of consciousness (awareness of the environment) with disturbance in attention (reduced ability to direct, focus, sustain attention); (2) a change in cognition (memory, orientation, language); (3) development over a short period of time (hours to days) and a tendency to fluctuate during the course of a day; and (4) evidence from history, physical, or laboratory findings that indicates the disturbance is caused by the direct physiological consequence of a general medical condition, intoxicating substance, medication use, or more than one cause.

Delirium is common and underdiagnosed. Patients with serious illness may be at higher risk for delirium given their underlying illness and other risk factors such as advanced age, sensory impairment, preexisting cognitive impairment, dehydration, immobility, multiple medications, and comorbid illness. Delirium point prevalence estimates are 4% to 12% in the community, 9% to 57% across hospital palliative care consultative services, and 6% to 74% in inpatient palliative care units. The prevalence of delirium prior to death across all palliative care settings is 42% to 88%. Delirium is associated with poor outcomes including loss of function, cognitive decline, increased hospital complications (e.g., delirious patients removing their intravenous lines, urinary catheters, oxygen delivery devices), increased institutional care, and increased risk of mortality. Among hospitalized older adults with delirium, 44% of patients have been found to have persistent delirium on discharge, 32.8% after 1 month, and 21% after 6 months. Both the hyperactive and hypoactive forms of delirium (see Chapter 28 ) are associated with patient, family, and clinician distress.

Relevant Pathophysiology

The pathophysiology of delirium is poorly understood. There are multiple proposed mechanisms that likely overlap, including neuroinflammation, neurotransmitter deficiency, and oxidative stress. Delirium lacks a single common final pathway that can be “treated” or modified with a medication. Multiple neurotransmitters (acetylcholine, dopamine, serotonin, gamma-aminobutyric acid [GABA], glutamate) have been implicated in the pathogenesis of delirium. It is thought that acetylcholine deficiency can precipitate delirium, as is frequently seen with anticholinergic drugs such as diphenhydramine. Dopamine excess may play a role in the pathogenesis of delirium as well.

Summary of Evidence Regarding Treatment Recommendations