HOW TO TREAT DELIRIUM NOT DUE TO ALCOHOL OR OTHER PSYCHOACTIVE SUBSTANCES 2025

GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF COMMON MENTAL DISORDERS

(Enacted under Decision No. 2058/QĐ-BYT dated May 14, 2020, by the Minister of Health)

Article 4

DELIRIUM NOT DUE TO ALCOHOL OR OTHER PSYCHOACTIVE SUBSTANCES

CHIEF EDITOR

Associate Professor, PhD Nguyễn Trường Sơn

CO-EDITOR

Associate Professor, PhD Lương Ngọc Khuê

PhD Nguyễn Doãn Phương

CONTRIBUTING AUTHORS

PhD Trần Thị Hà An

MSc Trịnh Thị Vân Anh

PhD Vũ Thy Cầm

MSc Trần Mạnh Cường

PhD Nguyễn Văn Dũng

PhD Vương Ánh Dương

PhD Lê Thị Thu Hà

MSc Trần Thị Thu Hà

MSc Phạm Công Huân

MSc Đoàn Thị Huệ

Specialist Doctor II Nguyễn Thị Minh Hương

MSc Vũ Thị Lan

1. Nguyễn Phương Linh

Specialist Doctor II Nguyễn Thị Phương Loan

MSc Bùi Văn Lợi

MSc Nguyễn Thị Phương Mai

PhD Trần Nguyễn Ngọc

MSc Bùi Nguyễn Hồng Bảo Ngọc

MSc Trương Lê Vân Ngọc

MSc Bùi Văn San

PhD Dương Minh Tâm

MSc Phạm Xuân Thắng

MSc Lê Thị Phương Thảo

MSc Lê Công Thiện

MSc Vương Đình Thủy

Associate Professor, PhD Nguyễn Văn Tuấn

Specialist Doctor II Ngô Văn Tuất

MSc Đặng Thanh Tùng

MSc Vũ Sơn Tùng

MSc Cao Thị Ánh Tuyết

MSc Nguyễn Thị Ái Vân

Specialist Doctor II Hồ Thu Yến

MSc Nguyễn Hoàng Yến

CONTRIBUTORS TO EVALUATION AND FEEDBACK

Associate Professor, PhD Nguyễn Thanh Bình

PhD Vũ Thy Cầm

PhD Nguyễn Hữu Chiến

Specialist Doctor II Võ Thành Đông

PhD Lê Thị Thu Hà

Specialist Doctor II Đỗ Huy Hùng

PhD Nguyễn Mạnh Hùng

MSc Nguyễn Trọng Khoa

Specialist Doctor II Ngô Hùng Lâm

Associate Professor, PhD Phạm Văn Mạnh

Specialist Doctor II Trần Ngọc Nhân

PhD Dương Minh Tâm

MSc Đặng Duy Thanh

PhD Vương Văn Tịnh

Specialist Doctor II Lâm Tứ Trung

PhD Lại Đức Trường

PhD Cao Văn Tuân

Associate Professor, PhD Nguyễn Văn Tuấn

SECRETARIAT TEAM

MSc Đặng Thanh Tùng

MSc Trương Lê Vân Ngọc

BA Đỗ Thị Thư

Article 4

DELIRIUM NOT DUE TO ALCOHOL OR OTHER PSYCHOACTIVE SUBSTANCES

I. DEFINITION

Delirium is a condition known by various terms, including acute confusional state, acute brain syndrome, metabolic encephalopathy, and toxic psychosis, but it is now uniformly referred to as delirium. According to the International Classification of Diseases, 10th Revision (ICD-10), and the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV), delirium is a syndrome characterized by a disturbance of consciousness, manifesting as reduced clarity of awareness of the environment, impaired ability to focus, sustain, or shift attention.

II. ETIOLOGY  

Delirium has numerous causes beyond alcohol and other psychoactive substances. These include:  

– Traumatic brain injury, brain tumors, epidural hematoma, abscess, intracranial hemorrhage, cerebral hemorrhage, non-hemorrhagic stroke, transient ischemic attack;  

– Metabolic disorders, electrolyte imbalances;  

– Diabetes mellitus, hypoglycemia, hyperglycemia, or insulin resistance;  

– Infections (e.g., sepsis, malaria, viral infections, plague, syphilis, abscess);  

– Medications such as analgesics, antibiotics, chemotherapeutic agents that may precipitate delirium;  

– Neuroleptic malignant syndrome, serotonin syndrome;  

– Severe systemic illnesses: hepatitis, renal failure, heart failure;  

– Nutritional deficiencies.  

III. DIAGNOSIS  

1. Definitive Diagnosis  

1.1. Clinical Features  

Characteristics of Delirium:

– Occurs at any age, most commonly in individuals over 60 years.  

– Syndrome characterized by simultaneous disturbances in consciousness, attention, perception, thinking, memory, psychomotor behavior, emotion, and sleep-wake cycle.  

– Most cases resolve within 4 weeks or less.  

To establish a definitive diagnosis, symptoms (mild or severe) must be present in each of the following domains:  

– Disturbance of Consciousness and Attention: Ranges from clouding of consciousness to coma; reduced ability to direct, focus, sustain, or shift attention.  

– Global Cognitive Impairment: Perceptual distortions, illusions, and hallucinations (predominantly visual); impaired abstract thinking and comprehension; transient delusions may occur, though typically with disorganized thought processes; immediate and recent memory impairment with relatively preserved remote memory; disorientation to time, place, and self in more severe cases.  

– Psychomotor Disturbances: Hypoactivity or hyperactivity; increased reaction time; increased or decreased speech flow; heightened startle response.  

– Sleep-Wake Cycle Disruption: Insomnia, or in severe cases, total sleep loss or reversal of the sleep-wake cycle with daytime somnolence; symptoms often worsen at night, potentially with nightmares.  

– Emotional Disturbances: Depression, anxiety, fear, irritability, euphoria, apathy, or bewildered perplexity.  

– Onset is typically acute, with fluctuating severity throughout the day, and the total duration is less than 6 months. The clinical presentation is sufficiently characteristic to allow a reliable diagnosis of delirium even if the underlying cause remains unclear. A history of underlying brain or systemic disease, along with evidence of brain dysfunction (e.g., abnormal EEG with slow-wave activity, though not always present), is required if the diagnosis is uncertain.  

1.2. Ancillary Testing  

The following tests may be ordered based on individual case presentation:  

– Blood Tests: Complete blood count (CBC), comprehensive metabolic panel (electrolytes, renal and liver function, thyroid function, glucose, D-dimer, ACTH stimulation test);  

– Arterial Blood Gas: Assess hypoxemia, hypercapnia, lactate levels;  

– Urinalysis;  

– Functional Studies: Electrocardiogram (ECG), electroencephalogram (EEG), cerebral blood flow studies, transcranial Doppler ultrasound;  

– Imaging Studies: Brain CT, MRI, abdominal ultrasound, chest/abdominal X-ray;  

– Toxicology Screen: Blood levels of digoxin, lithium, quinidine, alcohol, illicit drugs;  

– Cerebrospinal Fluid (CSF) Analysis: To detect encephalitis or meningitis;  

– Infectious Disease Testing: Syphilis serology, HIV antibody testing.  

Additional tests may be ordered as needed.  

ICD-10 Diagnostic Criteria:  

1. Clouded consciousness with reduced clarity of environmental awareness.  
2. Cognitive disturbance evidenced by both:  

   1) Impairment of immediate and recent memory, with remote memory spared;  

   2) Disorientation to time, place, or persons.  

1. At least one of the following psychomotor disturbances:  

   1) Rapid, unpredictable shifts between hyperactivity and hypoactivity;  

   2) Increased reaction time;  

   3) Increased or decreased speech flow;  

   4) Enhanced startle response.  

1. Sleep-wake cycle disturbance with at least one of:  

   1) Insomnia, total sleep loss in severe cases, or sleep-wake cycle reversal with daytime sleepiness;  

   2) Worsening of symptoms at night;  

   3) Disturbing dreams or nightmares.  

1. Acute onset with daily fluctuations.  
2. Evidence of an underlying brain or systemic condition, with brain dysfunction (e.g., abnormal EEG with slowed baseline activity, though not invariably present) required if diagnosis is uncertain.  
3. Differential Diagnosis  

– Dementia: Clinical features aid differentiation. Delirium has an acute, sudden onset, while dementia develops gradually and insidiously. Cognitive changes in dementia are stable, not fluctuating daily. Patients with dementia remain alert, whereas delirium often involves periods of impaired consciousness. Note that delirium can superimpose on pre-existing dementia.  

– Schizophrenia, Depression, or Mania: Hallucinations and delusions in schizophrenia are more persistent and systematic, without disturbances of consciousness or orientation. Hypoactive delirium may mimic depression, requiring differentiation via clinical assessment and EEG. These psychiatric conditions may also precipitate delirium due to neglect, exhaustion, or high-dose psychotropic medications.  

– Systemic Conditions: Cerebral infarction, myocardial infarction, acute infection, hypo-/hyperglycemia, hypoxemia, hypercapnia, acute urinary obstruction, drug/substance-related disorders, hepatic encephalopathy, renal failure, hyper-/hyponatremia, hypocalcemia, encephalitis/meningitis, brain tumors, post-stroke states, constipation, traumatic brain injury, Addison’s disease, thyrotoxicosis, hypothyroid coma, brain abscess, neurosyphilis, Wernicke’s encephalopathy.  

IV. TREATMENT  

1. Treatment Principles  

– Address Underlying Cause: Identifying and treating the precipitant of delirium is paramount.  

– Behavioral Control: Manage underlying causes if possible. Provide a familiar environment, calm interactions, and avoid confrontation.  

– Pharmacotherapy: Use medications to manage symptoms, typically at lower-than-standard doses, employing the lowest effective dose for the shortest duration possible.  

2. Treatment Framework  

– Treat the underlying cause;  

– Manage delirium symptoms;  

– Provide patient care and management.  

3. Specific Treatments  

3.1. Pharmacotherapy  

3.1.1. Cognitive Symptom Management  

Options include:  

– Donepezil: 5-23 mg/day;  

– Rivastigmine: 1.5-12 mg/day (oral or transdermal);  

– Galantamine: 8-24 mg/day.  

Agents studied for cognitive impairment (neurotrophic, metabolic, or cerebral circulation enhancers):  

– Cerebrolysin: 10-20 mL/day;  

– Ginkgo biloba: 80-120 mg/day;  

– Piracetam: 400-1200 mg/day;  

– Citicoline: 100-1000 mg/day;  

– Choline alfoscerate: 200-800 mg/day;  

– Vinpocetine: 5-100 mg/day;  

– Nicergoline: 10-30 mg/day;  

– Antioxidants: Vitamin E, selegiline.  

3.1.2. Antipsychotics  

Options (1-3 agents):  

– Risperidone: 1-10 mg/day;  

– Quetiapine: 50-800 mg/day;  

– Olanzapine: 5-30 mg/day;  

– Clozapine: 25-300 mg/day;  

– Aripiprazole: 10-30 mg/day;  

– Haloperidol: 0.5-20 mg/day.  

Note: For patients with Parkinson’s disease or Lewy body dementia with delirium, prefer antipsychotics with minimal exacerbation of parkinsonian symptoms (e.g., clozapine, quetiapine); avoid haloperidol.  

Insomnia Management: Short- or intermediate-acting benzodiazepines (e.g., lorazepam, zopiclone) are effective. Avoid long-acting benzodiazepines and barbiturates.  

Supportive Care: Essential for patients with delirium, addressing diverse underlying causes and comorbidities to minimize risks and improve outcomes. Elderly patients with delirium require care to reduce complications such as urinary incontinence, immobility, falls, pressure ulcers, dehydration, and malnutrition.  

Hepatic Support: Aminoleban, silymarin, boganic, branched-chain amino acids.  

Nutritional Support: Vitamins, minerals, balanced diet, IV nutrition as needed.  

3.2. Psychotherapy  

– Direct: Family therapy, individual psychotherapy;  

– Indirect:  

+ Ensure a safe environment for the patient and others;  

+ Maintain a quiet setting, minimizing external stimuli;  

+ Promote sleep hygiene;  

+ Educate families on caregiving and nutritional support.  

3.3. Physical and Occupational Therapy  

– Collaborate with rehabilitation specialists;  

– Goals: Restore motor function, provide speech therapy for language recovery.  

3.4. Treatment of Underlying or Comorbid Conditions  

– Medication-induced delirium;  

– Infections, metabolic disorders;  

– Conditions causing cerebral hypoxia (e.g., anemia, heart failure, COPD).  

3.5. Rehabilitation  

– Regularly assess basic daily functioning;  

– Create a familiar environment with frequent reminders of date, time, and location;  

– Involve family in caregiving and support;  

– Counsel families to recognize early signs of recurrence.  

V. PROGNOSIS AND COMPLICATIONS  

1. Prognosis  

– Symptoms persist until the underlying cause is resolved, typically lasting less than one week.  

– Prognosis worsens with advanced age.  

2. Complications  

– Related to the underlying condition;  

– Infections and trauma require monitoring and management.  

VI. PREVENTION  

– Optimize management of severe systemic illnesses to prevent delirium complications (e.g., provide a quiet, well-lit, safe environment).  

– Limit polypharmacy and avoid medications known to precipitate delirium.

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