What could cause sudden confusion and delusions in a stable adult psychiatric patient with a history of psychiatric illness, who was previously stable on psychiatric medications, including antipsychotics (e.g. risperidone) and other psychotropics?

Sudden Confusion and Delusions in a Previously Stable Psychiatric Patient

This is delirium until proven otherwise—a medical emergency requiring immediate investigation for underlying medical causes, as mortality doubles when delirium is missed. 1

Primary Diagnostic Framework: Delirium vs. Psychotic Relapse

The sudden onset of confusion and delusions in a previously stable psychiatric patient most likely represents delirium superimposed on chronic psychiatric illness, not simply medication failure or disease relapse. 1 The key distinguishing feature is that delirium presents with inattention and altered consciousness (even if subtle), while primary psychosis maintains intact awareness and level of consciousness. 1, 2

Delirium is a medical emergency with 8.1% overall mortality, rising significantly in elderly patients, and mortality doubles if the diagnosis is missed. 1

Most Common Precipitating Causes (In Order of Frequency)

1. Infections (Most Common)

• Urinary tract infections and pneumonia are the most frequent precipitating factors. 1
• Check vital signs, urinalysis with culture, chest X-ray, and complete blood count immediately. 1

2. Medication-Related Causes

• Opioids (64% of cases), benzodiazepines, corticosteroids, and paradoxically, antipsychotics themselves can cause delirium. 1
• Review all medications including over-the-counter drugs, recent dose changes, and new prescriptions. 1
• Anticholinergic burden from multiple medications is a critical but often overlooked cause. 1

3. Metabolic and Electrolyte Disturbances

• Hyponatremia, hypernatremia, hypoglycemia, hypercalcemia (especially with bone metastases in cancer patients), and hypoalbuminemia. 1
• Obtain comprehensive metabolic panel, calcium, magnesium, phosphate, and albumin. 1

4. Organ Dysfunction

• Hepatic encephalopathy, renal failure, cardiac failure, and respiratory failure with hypoxia. 1
• Check liver function tests, renal function, arterial blood gas if hypoxia suspected. 1

5. Substance Withdrawal

• Alcohol, benzodiazepines, or opioid withdrawal can present as hyperactive delirium with confusion and delusions. 1
• Obtain detailed substance use history including nicotine, as withdrawal can occur within 12 hours of last use. 1

6. Neurological Causes (Less Common but Critical)

• Nonconvulsive seizures, stroke, subdural hematoma, meningitis, encephalitis, or intracranial mass. 1
• Perform neurological examination looking for focal deficits, which mandate immediate neuroimaging. 2
• Consider EEG if seizure activity suspected, as it is the most sensitive method for detecting delirium. 3

7. Nutritional Deficiencies

• Vitamin B12 deficiency, thiamine deficiency (Wernicke's encephalopathy), and folate deficiency can cause acute psychotic symptoms and confusion. 4
• This is particularly important in patients with malnutrition, alcoholism, or advancing age. 4
• Check B12, folate, and thiamine levels; consider empiric thiamine replacement if alcoholism suspected. 4

8. Endocrine Disorders

• Thyroid dysfunction (hypo- or hyperthyroidism), Cushing's syndrome, Addison's disease. 1
• Obtain thyroid function tests and consider cortisol levels if clinically indicated. 1

Critical Clinical Pitfall

69% of delirious patients have multiple contributing factors (median of 3 causes), not a single etiology. 1 Do not stop investigating after finding one abnormality—continue the workup systematically.

Immediate Diagnostic Workup Algorithm

1. Vital signs (fever, hypoxia, hypotension, tachycardia) 1
2. Focused physical examination for infection sources, neurological deficits, signs of trauma 1, 2
3. Laboratory tests: Complete blood count, comprehensive metabolic panel, calcium, magnesium, phosphate, liver function, urinalysis with culture, B12, folate, thyroid function 1, 4
4. Medication review: All current medications, recent changes, over-the-counter drugs, substance use history 1
5. Chest X-ray if respiratory symptoms or hypoxia 1
6. Neuroimaging (CT or MRI brain) if focal neurological signs, head trauma history, or no clear medical cause identified 1, 2, 5
7. EEG if nonconvulsive seizures suspected or diagnosis remains unclear 1, 3
8. Lumbar puncture if meningitis/encephalitis suspected (after ruling out increased intracranial pressure) 1

Assessment Tools

Use Confusion Assessment Method (CAM) or CAM-ICU to objectively diagnose delirium, which requires: 1

• Acute onset with fluctuating course
• Inattention (cardinal feature)
• Either disorganized thinking OR altered level of consciousness

Management Principles

Treatment focuses on identifying and correcting the underlying cause(s), not simply sedating the patient. 1

• Start with non-pharmacological interventions: reorientation, familiar objects, adequate lighting, sleep hygiene, mobilization if safe. 1
• Antipsychotics (risperidone 0.5 mg or haloperidol 0.5-1 mg) should only be used if the patient has severe agitation posing risk to self or others, or distressing perceptual disturbances. 1, 6
• Benzodiazepines are contraindicated except for alcohol or benzodiazepine withdrawal, as they can worsen delirium. 1
• Avoid increasing psychiatric medications until medical causes are excluded and treated. 1

Special Consideration: Antipsychotics as Cause

Risperidone and other antipsychotics can themselves cause delirium, paradoxical agitation, and worsening confusion. 1 Consider whether recent dose increases or medication changes preceded the symptom onset.