When do we order lab or blood tests in patients presenting with psychiatric symptoms, particularly those with a history of substance abuse, medical comorbidities such as diabetes or hypertension, or those being treated with medications like lithium or valproate?

Laboratory Testing in Psychiatry: A Focused, History-Driven Approach

Laboratory testing in psychiatric patients should be selective and guided by clinical findings from history, physical examination, and vital signs rather than routine screening panels, as this approach identifies 94% of organic causes while routine testing has an extremely low yield (0.8-1.4%) when clinical assessment is normal. 1

Core Principle: Clinical Assessment Over Reflexive Testing

The American College of Emergency Physicians and American Academy of Pediatrics recommend focused medical assessment where laboratory testing is obtained based on history and physical examination rather than predetermined batteries for all psychiatric patients. 1 This evidence-based approach recognizes that:

• History alone has 94% sensitivity for identifying medical conditions in psychiatric patients 1, 2
• Physical examination adds 51% sensitivity 2
• Laboratory studies alone contribute only 20% sensitivity 2
• False positive results are 8 times more common than true positives when routine testing is performed without clinical indication 1

When to Order Laboratory Tests: Specific Clinical Triggers

High-Risk Populations Requiring Lower Testing Thresholds

Order targeted laboratory studies in these four groups identified by ACEP guidelines 1:

• Elderly patients (particularly psychogeriatric population) 1
• Patients with substance abuse history 1
• First psychiatric presentation (no prior psychiatric history) 1
• New or preexisting medical complaints 1
• Lower socioeconomic status 1

Abnormal Vital Signs or Physical Examination

Any abnormality mandates targeted workup 1:

• Fever: Check complete blood count, consider infectious workup 1
• Tachycardia: Obtain ECG, assess for medication effects (antipsychotics have odds ratio 4.09 for severe tachycardia), evaluate for QT prolongation 3
• Hypertension or hypotension: Check electrolytes, renal function 1
• Altered mental status or disorientation: Comprehensive metabolic panel, consider hyperammonemia workup 1, 3

Specific Clinical Presentations

Order glucose when: 4

• Hypoglycemia or hyperglycemia suspected from history
• Altered mental status present
• Diabetes history documented

Order electrolytes when: 4

• Medication use suggests metabolic disturbance (diuretics, lithium)
• Excessive water intake reported
• Vomiting, diarrhea, or dehydration present

Order complete blood count when: 4

• Fever present
• Immunocompromised status
• Infection suspected clinically

Order ammonia level when: 5

• Unexplained lethargy and vomiting develop
• Changes in mental status occur in patients on valproate
• Hypothermia present (can manifest hyperammonemia)

Medication-Specific Monitoring Requirements

Lithium Therapy

The FDA label mandates specific testing 6:

• Before initiation: Renal function, cardiovascular assessment
• Contraindicated in significant renal/cardiovascular disease, severe debilitation, dehydration, sodium depletion, or diuretic use
• Daily serum lithium levels required if treatment undertaken in high-risk patients

Valproate Therapy

FDA requirements include 5:

• Baseline: Platelet count, coagulation parameters, liver function
• Before surgery: Platelet count and coagulation studies
• During treatment: Monitor for thrombocytopenia (27% incidence at ~50 mg/kg/day)
• If lethargy/vomiting develops: Check ammonia level immediately
• Therapeutic drug monitoring: Plasma concentrations correlate with receptor occupancy and guide dosing 4

Antipsychotic Medications

Monitor for: 3

• QT prolongation (ECG if tachycardia, palpitations, or syncope)
• Metabolic syndrome parameters in chronic use
• Drug interactions via CYP system

What NOT to Order: Low-Yield Tests

Routine Urine Drug Screening

Multiple studies demonstrate minimal utility 1:

• Only 5% positive in routine screening with no changes in patient management 1
• Patient self-reporting has 92% sensitivity and 91% specificity for identifying positive drug screens 2
• Should only be ordered when results would change acute management or disposition 1

Routine Laboratory Panels

Avoid reflexive ordering of 1, 4, 7:

• Complete metabolic panels without clinical indication
• Complete blood counts in asymptomatic patients
• Thyroid function tests without suggestive symptoms
• Extensive screening batteries (yield only 1.1% clinically significant findings in patients with normal history/physical) 7

Special Considerations for Substance Abuse

In patients with substance abuse history 1:

• Lower threshold for targeted testing (this is a high-risk group)
• Consider specific toxicology only if results alter management
• Focus on complications: electrolytes for chronic alcohol use, cardiac monitoring for stimulant use
• Patient self-report is highly reliable (96% sensitivity for alcohol, 92% for drugs) 2

Medical Comorbidities: Diabetes and Hypertension

For patients with documented medical conditions 1:

• Diabetes: Check glucose if altered mental status, new psychiatric symptoms, or medication changes
• Hypertension: Monitor blood pressure, consider electrolytes if on diuretics or ACE inhibitors
• Both conditions increase cardiovascular risk—maintain lower threshold for cardiac evaluation if chest pain or palpitations 3

Critical Pitfalls to Avoid

Never assume psychiatric etiology without excluding organic causes in high-risk groups 3, 4. The most dangerous errors include:

• Dismissing tachycardia as "anxiety" without structured cardiac assessment 3
• Ordering extensive panels reflexively, leading to false positives and unnecessary workup 1, 4
• Delaying psychiatric evaluation waiting for unnecessary laboratory results in stable patients 4
• Missing hyperammonemia in valproate-treated patients with lethargy 5
• Failing to check lithium levels in patients with renal disease or dehydration 6

Cost-Effectiveness Evidence

One study found Medicare reimbursement for unnecessary ancillary testing totaled $37,682, with only 0.5% of tests changing disposition 8. Another demonstrated that screening without universal laboratory testing would have missed only 2 patients with mild, asymptomatic hypokalemia 2. This reinforces that clinical assessment drives appropriate resource utilization while maintaining patient safety.

Neurologic Red Flags Requiring Broader Evaluation

Order comprehensive workup including neuroimaging when 1, 3:

• Focal neurological deficits present
• First seizure or new seizure pattern
• Head trauma history with behavioral change
• Signs of increased intracranial pressure
• Acute stroke symptoms

The extensive list of neurologic, metabolic, endocrine, respiratory, and toxic causes that can present as psychiatric disorders 1 underscores why thorough history and physical examination remain the cornerstone of determining which specific tests to order.