What is the differential diagnosis for a 40-year-old male with a history of Generalized Anxiety Disorder (GAD) on Lexapro (escitalopram) 7.5 mg, presenting with acute onset paranoid delusions and fluctuating attention?

Differential Diagnosis for Acute Paranoid Delusions and Fluctuating Attention in a 40-Year-Old Male on Lexapro

Delirium is the most critical diagnosis to rule out immediately, as it is a medical emergency with doubled mortality if missed, and the combination of acute paranoid delusions with fluctuating attention strongly suggests impaired consciousness rather than primary psychosis. 1, 2

Primary Diagnostic Consideration: Delirium

This presentation demands urgent evaluation for delirium until proven otherwise. The acute onset and fluctuating attention are cardinal features that distinguish delirium from primary psychiatric disorders, which maintain intact consciousness and awareness. 3, 1, 2

Key Distinguishing Features

• Fluctuating attention and altered consciousness indicate delirium rather than primary psychosis, where awareness remains intact despite delusions. 3, 1
• Visual hallucinations (if present) are the strongest indicator of underlying medical cause rather than primary psychiatric disorder. 4
• Acute onset (hours to days) with symptoms that vary throughout the day points to delirium over chronic psychiatric conditions. 3, 2

Immediate Diagnostic Workup Required

Essential Laboratory Tests

• Complete blood count, comprehensive metabolic panel, urinalysis with culture to identify infections (UTI and pneumonia are most common precipitants). 1, 2
• Blood glucose, liver function tests, renal function, thyroid function tests to detect metabolic and organ dysfunction. 1, 2
• Toxicology screen and blood alcohol level to assess for substance intoxication or withdrawal. 1, 2

Clinical Assessment

• Confusion Assessment Method (CAM) should be used to objectively diagnose delirium, requiring: acute onset with fluctuating course, inattention, and either disorganized thinking or altered level of consciousness. 1, 2
• Obtain detailed history from knowledgeable informant about timeline of symptom onset, baseline cognitive function, and any recent changes. 3, 2
• Vital signs assessment for fever, tachycardia, hypotension, or hypoxia. 1, 2

Imaging Studies (Selective, Not Routine)

• Neuroimaging (CT or MRI) is indicated only if: focal neurological deficits present, recent head trauma, new onset seizures, signs of increased intracranial pressure, or unexplained altered mental status despite initial workup. 2
• Chest X-ray to evaluate for pneumonia. 1, 2

Differential Diagnosis by Category

1. Medication-Induced Causes (High Priority)

• Serotonin syndrome from escitalopram, though rare at 7.5 mg dose. 1
• SSRI-induced activation or paradoxical agitation, particularly if dose recently changed. 1
• Anticholinergic toxicity if patient taking other medications with anticholinergic properties. 1, 2
• Review ALL current medications including over-the-counter drugs, supplements, and recent additions or dose changes. 2

2. Infectious Etiologies

• Urinary tract infection (most common precipitant in adults). 1, 2
• Pneumonia (second most common infectious cause). 1, 2
• CNS infections (meningitis, encephalitis) - consider if fever, headache, or nuchal rigidity present. 4, 1

3. Metabolic and Electrolyte Disturbances

• Hyponatremia or hypernatremia (can cause acute confusion and psychosis). 1
• Hypoglycemia or hyperglycemia. 1, 2
• Hypercalcemia. 1
• Hepatic encephalopathy or renal failure. 1

4. Substance-Related Causes

• Alcohol withdrawal (assess drinking history and timing of last drink). 1, 2
• Benzodiazepine withdrawal (if patient has been using for anxiety). 1
• Stimulant intoxication (cocaine, amphetamines, synthetic cannabinoids). 1

5. Neurological Conditions

• Seizure or post-ictal state (can present with confusion and psychosis). 1, 2
• Stroke or transient ischemic attack (particularly if focal deficits present). 2
• CNS mass lesion or hemorrhage (consider if headache, focal signs, or recent trauma). 2

6. Autoimmune and Inflammatory Disorders

• Autoimmune encephalitis (anti-NMDA receptor encephalitis can present with psychiatric symptoms). 4, 1
• Systemic lupus erythematosus with neuropsychiatric manifestations. 4

7. Primary Psychiatric Disorders (Diagnosis of Exclusion)

• Brief psychotic disorder - but only after medical causes excluded. 5
• Delusional disorder - requires at least 1 month duration and exclusion of medical causes, mood disorders, and substance-induced toxicity. 5
• Worsening GAD with psychotic features - extremely rare; GAD does not typically present with delusions. 3
• New-onset schizophrenia or schizoaffective disorder - less likely given age 40 and acute onset. 5

Critical Clinical Pitfalls to Avoid

• Never dismiss symptoms as "just psychiatric" without adequate medical workup, as up to 46% of patients presenting with psychiatric symptoms have underlying medical disease. 4
• Do not attribute acute symptoms to pre-existing GAD without investigating for acute reversible causes, as delirium commonly occurs superimposed on chronic psychiatric conditions. 2
• Avoid increasing psychiatric medications until medical causes are excluded and treated, as antipsychotics themselves can cause or worsen delirium. 1
• Do not miss hypoactive delirium, which is frequently mistaken for depression or fatigue and is the most commonly missed delirium subtype. 2
• Without validated screening tools like CAM, clinicians fail to recognize delirium in the majority of cases. 2

Management Approach

• Treat the underlying cause rather than simply sedating the patient. 1
• Use antipsychotics judiciously only for severe agitation or distressing perceptual disturbances after medical causes addressed. 1
• Avoid benzodiazepines except for alcohol or benzodiazepine withdrawal. 1
• Implement non-pharmacological interventions: reorientation, familiar objects, adequate lighting, sleep hygiene, early mobilization. 1