What initial laboratory tests are recommended for patients presenting with restlessness and agitation?

Laboratory Evaluation for Restlessness and Agitation

For alert, cooperative patients with restlessness and agitation who have normal vital signs and a noncontributory history and physical examination, routine laboratory testing is unnecessary and should be guided by clinical findings rather than performed reflexively. 1

Initial Clinical Assessment Priorities

Before ordering any laboratory tests, the evaluation must focus on identifying specific clinical features that predict metabolic abnormalities:

• Check for altered mental status, fever, or focal neurological deficits - these findings mandate more extensive evaluation regardless of the agitation presentation 1
• Assess vital sign abnormalities - tachycardia, fever, hypertension, or hypotension suggest organic causes requiring targeted testing 1
• Evaluate cognitive function - disorientation or confusion indicates possible delirium and necessitates broader metabolic workup 1
• Identify high-risk populations - elderly patients, those with substance abuse history, patients without prior psychiatric history, and those with new medical complaints require more thorough evaluation 1

Selective Laboratory Testing Based on Clinical Indicators

Core Tests When Clinically Indicated

Serum glucose should be checked if there is any suspicion of hypoglycemia or hyperglycemia based on history (diabetes, medication use, poor oral intake) or examination findings 1, 2

Serum sodium is indicated when hyponatremia is suspected based on medication use (diuretics, SSRIs), excessive water intake, or clinical presentation suggesting electrolyte disturbance 1, 2

Complete blood count (CBC) should be ordered when infection is suspected based on fever, leukocytosis risk factors, or immunocompromised status 1, 2

Basic metabolic panel is warranted in patients with known renal disease, medication use affecting electrolytes, or clinical signs of metabolic derangement 1, 2

Additional Testing for Specific Clinical Scenarios

Thyroid function tests should be considered in patients with affective symptoms, particularly in women, as thyroid disease can present with agitation 1

Calcium and magnesium levels are indicated in patients with malnutrition, chronic alcohol use, renal insufficiency, or those taking diuretics 1, 2

Liver function tests should be checked in patients with known hepatic disease or chronic alcohol use, as hepatic encephalopathy can present with agitation 1

Pregnancy test is essential in women of childbearing age, as it affects diagnostic approach and medication choices 1, 2

Toxicology Screening Considerations

Urine Drug Screen Limitations

Routine urine toxicology screening is not recommended for medical clearance in alert, cooperative patients with psychiatric complaints and normal vital signs 1

• False-positive results occur 8 times more frequently than true positives (1.8%) in routine screening 1
• The sensitivity for detecting organic causes of agitation is only 20% when used routinely 1
• Most clinically significant substance use is identified through history and physical examination 1

When Toxicology Testing Is Appropriate

Targeted drug screening should be considered in specific circumstances:

• First-time presentation of agitation without prior psychiatric history 1
• Clinical presentation consistent with specific toxidromes (anticholinergic, sympathomimetic, sedative-hypnotic) 3, 4
• Suspected serotonin syndrome, which is frequently overlooked and can present with agitation 4
• Altered mental status beyond simple agitation 1
• Requirement by receiving psychiatric facility for admission 1

Serum alcohol level is more useful than urine testing when substance use is suspected, as it provides quantitative information for clinical decision-making 4

Special Population Considerations

Elderly Patients

Older adults require more cautious evaluation due to higher risk of organic causes:

• Lower threshold for checking electrolytes, particularly sodium and calcium 1
• Consider vitamin B12 and folate levels in those with cognitive changes 1
• Medication review is critical, as polypharmacy commonly causes agitation 1

Pediatric and Adolescent Patients

Children and adolescents with psychotic symptoms or severe agitation require comprehensive medical evaluation to exclude organic causes 1:

• CBC, serum chemistry studies, thyroid function tests, and urinalysis should be considered 1
• Toxicology screens are appropriate given high rates of substance abuse (up to 50% comorbidity in adolescents with psychotic symptoms) 1
• Chromosomal analysis may be indicated if developmental syndrome features are present 1

Substance Use Populations

Alcohol withdrawal seizures should be diagnosed by exclusion, particularly in first-time presentations 1

• Magnesium levels should be checked in suspected alcohol-related presentations 2
• If psychotic symptoms persist longer than one week despite documented detoxification, consider primary psychiatric disorder rather than substance-induced psychosis 1

Critical Pitfalls to Avoid

Do not order extensive routine laboratory panels reflexively - studies consistently show that history and physical examination predict 83-98% of clinically significant abnormalities 1

Do not assume psychiatric etiology without excluding medical causes in high-risk groups (elderly, first presentation, abnormal vital signs, substance abuse history) 1

Do not overlook serotonin syndrome - this diagnosis is frequently missed in agitated patients taking SSRIs or multiple serotonergic medications 4

Do not delay treatment while awaiting laboratory results in severely agitated patients requiring immediate intervention for safety 5

Recognize that benzodiazepines are surprisingly common in agitated patients, often in combination with alcohol, and may not be suspected clinically 4