Delirium: Symptoms, Causes, Diagnosis, and Treatment

What is Delirium?

Delirium is an acute neuropsychiatric syndrome in which a patient loses awareness of their surroundings and enters a state of mental confusion. It appears suddenly, often within hours or days, and involves fluctuating disturbances in consciousness, attention, cognition, and sometimes perception.

By definition, delirium is an acute condition, distinguishing it from the chronic nature of most psychiatric disorders. This is also one of the key features that separates it from dementia, though the two conditions can coexist. This overlap is particularly common in elderly patients.

Patients who develop delirium experience problems across multiple cognitive and behavioral domains:

• Attention: difficulty sustaining or directing focus
• Thinking: disorganized, fragmented, illogical thought processes
• Awareness: reduced awareness of the surrounding environment
• Behavior: agitation, restlessness, or conversely withdrawal and passivity
• Emotions: fear, anxiety, sadness, or emotional lability
• Judgment: impaired reasoning and decision-making
• Memory: particularly impaired formation of new short-term memories
• Motor control: tremor, myoclonus, or asterixis (flapping tremor)
• Sleep-wake cycle: disruption of the normal circadian rhythm

The Three Subtypes of Delirium

Clinicians recognize three distinct presentations:

1. Hyperactive delirium: The patient is agitated, restless, combative, and may attempt to remove IV lines, catheters, or monitoring equipment. They may shout, pace, or be frankly aggressive. This subtype is the most recognizable. It is also the most dangerous, particularly when considering immediate behavioral consequences.

2. Hypoactive delirium: The patient appears lethargic, excessively tired, somnolent, or withdrawn. This subtype is far more commonly missed or misattributed, often mistaken for depression, fatigue, or simply “aging”. It carries a worse prognosis for this very reason: it frequently goes unrecognized and untreated.

3. Mixed delirium: The patient fluctuates between hyperactive and hypoactive features within the same episode. This is actually the most common clinical presentation.

Understanding these subtypes matters because the quiet patient with hypoactive delirium requires the same urgent clinical attention as the agitated one. However, they are far less likely to receive it.

Delirium vs. Dementia vs. Delusion: Key Distinctions

These three terms are frequently confused:

• Delirium: Acute, sudden onset, fluctuating course, altered consciousness, identifiable medical cause, generally reversible.
• Dementia: Chronic, insidious progressive decline in multiple cognitive domains, consciousness generally preserved until late stages, typically irreversible.
• Delusion: A fixed false belief, a symptom of psychiatric illness, that does not involve the acute fluctuating confusion of delirium.

The practical clinical implication: an acute change in a cognitively impaired patient should always prompt evaluation for delirium, not simply be attributed to their dementia. Conversely, symptoms of delirium in a previously cognitively intact patient should never be dismissed as “just confusion”.

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Causes and Risk Factors

Delirium is not a disease in itself. Instead, it is a syndrome, meaning a pattern of symptoms that result from disruption of normal brain signaling. The underlying mechanisms involve widespread dysfunction in neurotransmission (particularly acetylcholine, dopamine, and other systems), neuroinflammation, and impaired cerebral metabolism.

Predisposing Risk Factors

The two most important baseline risk factors are:

• Advanced age (>65 years): The aging brain has reduced physiological reserve and is more vulnerable to perturbation. Neuronal loss, reduced neurotransmitter synthesis, altered pharmacokinetics, and the accumulation of comorbidities all contribute.
• Pre-existing cognitive impairment or dementia: Patients with dementia are two to five times more likely to develop delirium when hospitalized, and when they do, delirium is more severe, more prolonged, and harder to distinguish from baseline.

Additional predisposing factors include:

• Functional limitations in daily activities (immobility, dependence)
• Sensory impairments (visual and hearing loss)
• Malnutrition and/or dehydration
• Severe, chronic, or terminal illness
• History of previous delirium
• Social isolation and unfamiliar environments

Precipitating Triggers

In a vulnerable patient, delirium can be triggered by virtually any acute physiological disruption. The most clinically important precipitants include:

Medications

Polypharmacy is one of the most common and preventable causes of delirium in older adults. High-risk medications include:

• Sedative-hypnotics (benzodiazepines, Z-drugs, barbiturates): particularly implicated in delirium; promote sedation while paradoxically impairing normal sleep architecture.
• Opioid analgesics: particularly meperidine/pethidine, which produces a toxic metabolite that is directly neurotoxic
• Antidepressants: especially those with significant anticholinergic activity (tricyclics).
• Anticholinergic agents broadly: including bladder antispasmodics, first-generation antihistamines, some antipsychotics, and antispasmodics. The anticholinergic burden, which refers to the cumulative anticholinergic effect of all medications a patient is taking, is an important consideration in older patients.
• Medications for Parkinson’s disease: dopaminergic agents can cause hallucinations and confusion.
• Anticonvulsants: particularly at high doses or in the context of toxicity.
• Steroids, fluoroquinolone antibiotics, and antiviral agents are less commonly implicated but recognized precipitants.

Substances

• Alcohol: both acute intoxication and, critically, alcohol withdrawal (delirium tremens, a life-threatening medical emergency)
• Illicit drugs: stimulants, hallucinogens, and cannabis can precipitate acute confusion
• Poisons: including carbon monoxide poisoning

Medical Conditions

• Organ failure: hepatic, renal, cardiac, and respiratory failure all produce metabolic derangements that impair brain function
• Metabolic disturbances: significant abnormalities in blood glucose (hypoglycemia or hyperglycemia), electrolytes (sodium, calcium, magnesium), or acid-base balance
• Severe vitamin B12 deficiency: can cause subacute combined degeneration of the spinal cord and encephalopathy
• Infections: Any significant infection, such as a urinary tract infection, pneumonia, sepsis, meningitis, or encephalitis, can precipitate delirium. This is especially true in older adults. (Notably, urinary tract infection in elderly patients may present with delirium as the sole manifestation, with minimal or absent classic urinary symptoms.)
• Neurological events: stroke, transient ischemic attack, subdural hematoma, vasculitis, seizures and post-ictal states
• Thyroid disorders: both severe hypothyroidism (myxedema coma) and hyperthyroidism (thyroid storm)
• Surgery: the peri-operative period is a particularly high-risk time, due to the combined effects of anesthesia, pain, sleep disruption, immobility, and physiological stress
• Severe emotional or psychological stress
• Terminal malignancy: advanced cancer with metabolic complications, hypercalcemia, paraneoplastic syndromes, or the direct effects of brain metastases

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Symptoms

The symptoms of delirium typically appear suddenly, often within hours, and their intensity fluctuates throughout the day. They almost always worsen in the evening and at night, a pattern known as “sundowning”. This term is also used in dementia, however.

Early Warning Signs

Early or subtle signs that may precede a full delirium episode include:

• Sudden changes in personality or usual behavior
• Uncharacteristic anxiety or irritability
• Unusual quietness or withdrawal (hypoactive subtype)
• Difficulty concentrating or following conversations

These early signs can be easily missed. This is especially true for the hypoactive subtype, which may initially resemble fatigue, depression, or natural aging.

Disturbances of Consciousness and Attention

• Inability to focus or sustain attention: The patient is easily distracted, cannot maintain concentration, and may become fixed on an irrelevant stimulus
• Disorientation: Confusion about where they are, who the people around them are, or the time of day
• Reduced environmental awareness: The patient appears “absent” or disconnected from their surroundings

Cognitive Disturbances

• Memory impairment: Particularly for recent events; the patient may not recall conversations from minutes earlier
• Disorientation: To place, time, and occasionally person
• Language difficulties: Problems finding words, producing nonsensical speech, difficulty understanding what is said to them
• Reading and writing difficulties: Both expressive and receptive communication impaired

Behavioral and Emotional Disturbances

• Hallucinations: Most commonly visual, such as seeing things that are not there, and they represent a highly characteristic feature of delirium. Tactile hallucinations (the feeling of insects on the skin) are particularly common in alcohol withdrawal delirium.
• Agitation, irritability, or aggression (hyperactive subtype)
• Total or partial apathy with minimal response to environmental stimuli (hypoactive subtype)
• Sleep disturbance: Complete disruption of the sleep-wake cycle; the patient may be awake and agitated at night and deeply somnolent during the day
• Emotional extremes: Intense fear, anxiety, anger, or depression, often shifting rapidly from one to another.

How to Distinguish Delirium from Dementia

This distinction is clinically critical and is one of the most frequent diagnostic challenges in geriatric medicine:

A practical implication: if a patient with known dementia shows a sudden, acute change in mental status, assume delirium until proven otherwise. The temptation to attribute worsening to the dementia itself is a common and dangerous error.

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Prognosis

The prognosis of delirium is a subject of increasing clinical concern, with accumulating evidence suggesting that its consequences extend far beyond the immediate acute episode.

Short-Term Prognosis

• Delirium in hospitalized patients is associated with a doubled mortality risk compared to matched patients without delirium, independent of other clinical factors (Leslie et al., 2011).
• In ICU settings, delirium is associated with increased mechanical ventilation duration, longer hospital stays, and greater functional decline at discharge.
• For most patients, when the underlying cause is identified and effectively treated, improvement begins within 24 to 72 hours. Full recovery, including a return to baseline cognitive function, occurs over days to weeks.
• However, in elderly patients with pre-existing comorbidities (dementia, traumatic brain injury, or significant frailty), recovery may take weeks and may not be complete.

Long-Term Prognosis and Relationship to Dementia

The long-term relationship between delirium and cognitive decline is one of the most active areas of research in geriatric medicine:

• Prospective studies of hospitalized patients (independent of delirium status) suggest increased subsequent dementia risk, but methodological limitations complicate interpretation.
• In the only prospective population-based study specifically examining delirium, older adults who experienced delirium had an eightfold increase in subsequent dementia incidence. They also demonstrated significantly accelerated cognitive decline. These findings persisted even after controlling for baseline cognitive function. This association was equally evident in patients with pre-existing Alzheimer’s disease, in whom delirium was associated with substantially faster progression.

Whether delirium causes neuronal injury and accelerates dementia, or whether it simply unmasks pre-existing but subclinical neurodegeneration, remains an open research question. The clinical implication, however, is clear: an episode of delirium should be considered a marker of brain vulnerability, warranting careful cognitive follow-up.

Memory After Delirium

Some patients retain no memory of the delirium episode itself. Others often recall only fragments, like distant dreams. Some remember hallucinations or confused thoughts that still trouble them, even after they recover. Both outcomes are normal; patients and families should be prepared for either.

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When to Call a Doctor

Any sudden change in a person’s mental state, including confusion, disorientation, unusual behavior, or altered consciousness, should prompt immediate medical evaluation. This guideline applies even if the person has a known dementia or another chronic condition.

The following specific situations call for immediate attention:

• A cognitively intact person suddenly becomes confused, disoriented, or agitated.
• A person with known dementia who exhibits an acute change in their usual level of attention, alertness, or behavior should be considered delirious until proven otherwise.
• Confusion accompanies fever, signs of infection, pain, or any recent change in medication.
• The patient is attempting to remove medical equipment, is in danger of falling, or is agitated to the point of harm.

In the hospital or care home setting, do not assume that staff have already noticed a change. Hypoactive delirium in particular is frequently missed. If you observe changes as a family member or visitor, actively communicate your concerns to the nursing staff or physician. Your observations, since you know the patient’s baseline, are diagnostically invaluable.

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Risks and Complications

The longer delirium lasts, or the more severe it becomes, the greater the risk of lasting harm. The most important complications include:

• Accelerated cognitive decline: As discussed above, particularly in older adults and those with pre-existing dementia
• Incomplete recovery: Patients with serious, chronic, or terminal illness may not return to their pre-delirium level of cognitive or functional capacity
• Increased surgical complications: Delirium after surgery is associated with impaired wound healing, greater rates of complications, and longer recovery
• Falls and physical injury: Hyperactive delirium dramatically increases fall risk; attempted removal of catheters and IV lines can cause bleeding and infection
• Prolonged hospitalization and nursing home placement: Patients who develop delirium during hospitalization have longer stays and are more likely to require institutional care on discharge
• Increased mortality: Particularly in patients with serious comorbidities, delirium is an independent predictor of death

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Diagnosis

Because delirium symptoms fluctuate, it may not be immediately apparent on a single clinical assessment. Diagnosis relies on clinical judgment supported by validated assessment tools and targeted investigations.

Clinical Assessment

History from informants: Given the patient’s impaired capacity to provide a reliable history, information from family members, carers, and nursing staff is often the most important diagnostic input. Key questions: What is the patient’s baseline cognitive function? When did the change begin? How rapidly did it develop? What medications is the patient taking? Any recent illness, falls, or changes in eating/drinking?

Validated assessment tools:

• Confusion Assessment Method (CAM): The most widely used bedside tool, designed to be administered by non-psychiatrist clinicians. Diagnoses delirium based on: acute onset and fluctuating course, inattention, disorganized thinking, and altered level of consciousness. Sensitivity approximately 94%, specificity approximately 89%.
• CAM-ICU: An adaptation of the CAM for use in patients who cannot speak (e.g., those on mechanical ventilation).
• 4AT (Four ‘A’s Test): A rapid, validated screening tool for delirium that takes under 2 minutes to administer, particularly useful in emergency and acute settings.

Neurological examination: This assessment evaluates vision, balance, coordination, and reflexes. Its purpose is to identify potential causes such as stroke, encephalitis, or other neurological conditions.

Mental status assessment: Orientation, attention, memory, language, and executive function.

Differential Diagnosis

Conditions that must be actively excluded include:

• Dementia (key differentiating feature: dementia has insidious onset; delirium is acute)
• Depression (particularly in hypoactive delirium)
• Bipolar disorder: manic episode
• Schizophrenia
• Non-convulsive status epilepticus
• Stroke or transient ischemic attack

Investigations

Laboratory and imaging studies are selected based on clinical suspicion of underlying causes:

• Blood tests: Full blood count (infection, anemia), electrolytes (hyponatremia, hypernatremia, hypo/hyperkalemia, hypercalcemia), renal function, liver function, blood glucose, thyroid function (TSH), vitamin B12, ammonia (if hepatic encephalopathy suspected), toxicology screen
• Urinalysis and urine culture: UTI is a frequent precipitant, especially in older women
• Chest X-ray: Pneumonia, pulmonary edema
• CT head or MRI brain: When stroke, subdural hematoma, or intracranial pathology is suspected
• Lumbar puncture and CSF analysis: When meningitis or encephalitis is in the differential
• Electroencephalogram (EEG): To exclude non-convulsive status epilepticus; also shows characteristic diffuse slowing in metabolic delirium

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Treatment

The fundamental principle of delirium management is straightforward: identify and treat the underlying cause. This is the only intervention that addresses the root of the problem. Symptomatic pharmacological treatment is an important adjunct but cannot substitute for treating the precipitant.

Supportive (Non-Pharmacological) Care

Non-pharmacological interventions are the first-line approach for delirium management and prevention, and have the most robust evidence base for improving outcomes without the risks associated with medications. These measures focus on:

Reorientation and Cognitive Support

• Prominently visible clocks and calendars: To help the patient maintain temporal orientation
• Regular, clear communication: Identify yourself by name each time you interact. Calmly remind the patient where they are, what day it is, and what is happening around them.
• Familiar objects from home: Personal photographs, a familiar blanket, or cherished objects provide sensory anchors to the patient’s normal identity and environment
• Consistent caregivers: Where possible, minimize the number of different staff members interacting with the patient, as unfamiliar faces increase disorientation
• Avoid sudden environmental changes: The hospital environment is inherently disorienting; minimize unnecessary room or ward changes

Sleep-Wake Cycle Optimization

• Daytime light exposure: Open blinds and curtains during the day to support the circadian rhythm.
• Activity during the day: Encourage the patient to sit up, mobilize, and engage in daytime activities. This helps prevent daytime somnolence, which can disrupt nighttime sleep.
• Quiet, dark nights: Minimize nighttime noise and light interruptions; avoid unnecessary nighttime observations or interventions where clinically safe.
• Pre-sleep routine: A warm, non-caffeinated drink and relaxation before sleep; music therapy and massage have demonstrated benefit in reducing nighttime agitation.

Sensory Correction

• Ensure glasses and hearing aids are in use: Sensory impairment dramatically worsens disorientation. A patient who cannot hear or see clearly will struggle to process their environment accurately.
• Adequate lighting for daytime activities.

Mobility and Physical Independence

• Encourage early mobilization: Getting out of bed, walking, and performing self-care tasks as soon as clinically safe.
• Remove physical restraints: Physical restraints (wrist ties, vest restraints) are strongly associated with worsening agitation and delirium; they should be avoided except in cases of immediate danger, and then only as a last resort.
• Remove unnecessary catheters: Indwelling urinary catheters are a known delirium precipitant, as they increase infection risk and cause discomfort. Remove them as soon as clinically indicated.

Family Involvement

• Active family presence: Familiar faces and voices are profoundly grounding for a confused patient. Family members who remain calm and supportive play a crucial role in reorientation.
• Psychoeducation: Family members should be educated about what delirium is, why it happens, and that it is typically not permanent. This reduces their distress and helps them interact constructively.

Other Supportive Measures

• Adequate hydration and nutrition: Address dehydration and nutritional deficits promptly, as both can directly precipitate issues.
• Pain management: Unrecognized or inadequately managed pain is a common but easily overlooked delirium precipitant; assess and treat systematically.
• Constipation prevention and management: Urinary retention and fecal impaction cause significant discomfort and can precipitate or worsen delirium.
• Relaxation techniques: Music therapy, gentle massage, and aromatherapy have been studied as adjuncts to reduce agitation in delirium. Some evidence supports their effectiveness.

Pharmacological Treatment

Medications for delirium are used adjunctively; their purpose is to manage agitation and distressing behavioral symptoms while the underlying cause is being treated. They should be used at the lowest effective dose for the shortest necessary duration.

Important: There is currently no medication with strong evidence that it prevents or shortens delirium duration when administered prophylactically. Pharmacological treatment is reserved for symptomatic management when behavioral symptoms cannot be adequately managed with non-pharmacological approaches alone.

Antipsychotics

Haloperidol (a first-generation antipsychotic) remains the most studied agent for delirium agitation management. It can be administered orally, intramuscularly, or intravenously, and has a relatively rapid onset. It reduces agitation and psychotic symptoms but does not address the underlying mechanism of delirium. QTc prolongation monitoring is required.

Second-generation (atypical) antipsychotics, including quetiapine (Seroquel), risperidone, olanzapine, and aripiprazole, are increasingly used as alternatives or adjuncts. These medications may cause fewer extrapyramidal side effects. Quetiapine is particularly used in agitated delirium, both for its antipsychotic effects and its sedating properties at lower doses, which can assist with sleep-wake cycle restoration.

Note on Quetiapine vs. Seroquel: Seroquel is the brand name; quetiapine is the generic active ingredient. At equivalent doses, they are pharmacologically identical.

Caution in Lewy body dementia: Antipsychotics, particularly typical antipsychotics, are contraindicated or require extreme caution in patients with Lewy body dementia. These medications can provoke severe and potentially fatal antipsychotic sensitivity reactions in such patients.

Special Situations

• Alcohol withdrawal delirium (delirium tremens): Benzodiazepines are the treatment of choice. In this specific context, their use is evidence-based and potentially life-saving. The general avoidance of benzodiazepines in delirium does not apply here.
• Opioid-induced delirium: Consider opioid dose reduction, opioid rotation, or, in appropriate cases, careful use of opioid antagonists.

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Prevention

Research consistently shows that many cases of delirium, especially in hospitals, can be prevented. Estimates suggest that targeted multicomponent prevention programs can prevent up to 30–40% of all delirium cases, representing a substantial reduction in suffering, hospital complications, and healthcare costs.

Identifying High-Risk Patients

Prevention begins with identifying patients at elevated baseline risk:

• Age >65 years
• Pre-existing dementia or cognitive impairment
• History of previous delirium
• Hip fracture or other major trauma
• Severe, debilitating, or terminal illness
• Significant sensory impairment
• Malnutrition or dehydration

For these patients, proactive monitoring and early implementation of non-pharmacological prevention strategies (as described above) should begin immediately on admission.

Evidence-Based Prevention Strategies

The Hospital Elder Life Program (HELP), developed at Harvard Medical School, is the most rigorously studied multicomponent delirium prevention intervention. It combines the non-pharmacological approaches described throughout this guide (reorientation, sleep optimization, early mobilization, sensory correction, adequate hydration) into a systematic daily protocol, delivered by trained volunteers and staff. Multiple randomized controlled trials have demonstrated significant reductions in delirium incidence and duration through this approach.

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How to Manage the Situation at Home or in Hospital

Whether a loved one is in the hospital recovering from delirium or at home with a condition that predisposes to it, the following practical guidance will help caregivers provide optimal supportive care:

Promoting Good Sleep

• Adjust indoor lighting to match the time of day: keep it bright during the day and dim at night
• Encourage physical activity and engagement during waking hours
• Offer a warm, relaxing, non-caffeinated drink before bed
• Minimize noise and light disturbance during sleep hours

Maintaining Calm and Orientation

• Keep a clock and calendar visible and refer to them regularly during the day.
• Communicate any change in schedule simply and in advance (“It’s nearly lunchtime, we’re going to eat soon”).
• Keep familiar, cherished objects within easy reach, but be mindful of excessive clutter.
• Speak calmly and patiently; introduce yourself by name each time if needed.
• Avoid arguments or attempts to correct delusional statements directly. Instead, redirect gently.
• Minimize background noise and unnecessary distractions.
• Help the patient follow a consistent daily routine.
• Ensure glasses and hearing aids are clean, functional, and in use.

Preventing Complications

• Administer medications on a regular, consistent schedule
• Offer frequent fluids and encourage a healthy, varied diet
• Encourage and support physical movement and activity as tolerated
• Monitor for signs of recurrence and seek prompt medical attention if they appear

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Frequently Asked Questions

How long does it take to see results from pharmacological treatment for delirium?

Response time to pharmacological treatment varies considerably between patients. Generally, initial improvement, particularly in behavioral agitation, may be observable within 24–72 hours of starting antipsychotic medication. Complete resolution of the delirium episode may take from a few days to several weeks, depending on the nature of the precipitating cause, the patient’s age, and their overall health status. Crucially, pharmacological treatment must always be accompanied by treatment of the underlying cause. Without addressing the precipitant, drug treatment alone cannot produce lasting improvement.

What is the difference between Quetiapine and Seroquel?

Seroquel is the brand name of the medication; quetiapine is the generic name (active ingredient). At equivalent doses, they are pharmacologically identical. When a physician prescribes quetiapine, a pharmacy may dispense either the branded or generic version, as both are equivalent.

Can people with anxiety develop delirium?

Anxiety alone is not a significant risk factor for delirium in otherwise healthy individuals. However, in the context of a medical illness, hospitalization, or substance withdrawal, anxiety may be both a symptom of developing delirium and a factor that worsens its course. If a person with anxiety suddenly experiences acute confusion or disorientation, especially during illness or significant physiological stress, they should seek prompt medical evaluation.

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Bibliography and Sources

• National Cancer Institute. Delirium (PDQ) Patient Version
• Mayo Clinic. Delirium: Symptoms and Causes
• Inouye, S.K., Westendorp, R.G.J., & Saczynski, J.S. (2014). Delirium in elderly people. The Lancet, 383(9920), 911–922. https://doi.org/10.1016/S0140-6736(13)60688-1
• Leslie, D.L., & Inouye, S.K. (2011). The importance of delirium: economic and societal costs. Journal of the American Geriatrics Society, 59(Suppl 2), S241–S243. https://pubmed.ncbi.nlm.nih.gov/20664045/
• Davis, D.H.J., et al. (2012). Delirium is a strong risk factor for dementia in the oldest-old: a population-based cohort study. Brain, 135(9), 2809–2816. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437024/
• Jackson, T.A., et al. (2016). Delirium as a novel frontier in frailty research. BMC Geriatrics. https://pubmed.ncbi.nlm.nih.gov/20179286/
• National Institute for Health and Care Excellence (NICE). (2019). Delirium: prevention, diagnosis and management. NICE Clinical Guideline CG103.
• Young, J., & Inouye, S.K. (2007). Delirium in older people. BMJ, 334(7598), 842–846.
• Agar, M.R., et al. (2017). Efficacy of oral risperidone, haloperidol, or placebo for symptoms of delirium among patients in palliative care: a randomized clinical trial. JAMA Internal Medicine, 177(1), 34–42.