What lab tests are recommended for a comprehensive workup for depression?

Recommended Laboratory Tests for Depression Workup

A comprehensive depression workup should include thyroid-stimulating hormone (TSH), complete blood count (CBC), basic metabolic panel, liver function tests, and vitamin B12 levels to rule out medical conditions that can mimic or exacerbate depression. 1

Core Laboratory Tests

Essential Tests

• Thyroid Function Tests

  • TSH (primary screening test)
  • Free T4 (if TSH is abnormal)
  • Free T3 (if indicated by abnormal TSH/T4)

• Complete Blood Count (CBC)

  • To screen for anemia, infection, or other hematologic abnormalities

• Basic Metabolic Panel

  • Electrolytes (sodium, potassium, chloride, bicarbonate)
  • Blood urea nitrogen (BUN)
  • Creatinine
  • Glucose

• Liver Function Tests

  • AST, ALT, bilirubin

• Vitamin B12 Level

  • Deficiency can present with depressive symptoms

Additional Tests Based on Clinical Presentation

• Urinalysis and toxicology screen

  • Particularly important if substance use is suspected 1

• Electrocardiogram (ECG)

  • Especially if considering tricyclic antidepressants or in older adults

Rationale and Evidence

Thyroid Function Testing

Thyroid dysfunction has a well-established relationship with mood disorders. Studies show that:

• 5.3% of depressed inpatients have subclinical hypothyroidism 2
• Patients with TSH in the upper 25th percentile of normal range are more likely to have recurrent depression, longer disease duration, and more suicide attempts 2
• Lower values of FT3 and FT4 can predict poor clinical outcomes in depression 3

While some older studies found limited value in routine thyroid screening (only 0.4% of cases with overt hyperthyroidism and no overt hypothyroidism) 4, more recent evidence supports thyroid testing as an important component of depression workup.

Ruling Out Medical Conditions

The USPSTF guidelines emphasize the importance of accurate diagnosis following positive depression screening 1. Laboratory testing helps identify medical conditions that can:

1. Mimic depression symptoms
2. Exacerbate underlying depression
3. Affect treatment selection and response

For example, poststroke cognitive impairment can present with depressive symptoms, and the workup should include electrolytes, liver and renal function tests, and assessment for infection 1.

Special Considerations

Age-Related Factors

• Older adults: More comprehensive testing may be needed due to higher prevalence of medical comorbidities and medication use
• Adolescents: While the same laboratory tests are recommended, the predictive value of positive screening tests is lower 1

Treatment Implications

Laboratory findings may influence treatment selection:

• Patients with blunted TSH response to TRH challenge may respond better to SSRIs than tricyclic antidepressants 5
• Changes in thyroid hormone levels (T4 and FT4) after treatment differ between responders and non-responders 5

Common Pitfalls to Avoid

1. Overlooking subclinical thyroid dysfunction: Even thyroid values within "normal" range but at the extremes may be clinically significant in depression 2

2. Failing to repeat testing: Laboratory values may change during treatment, and monitoring (especially thyroid function) may be necessary

3. Misinterpreting results: Not all abnormal findings indicate causation; correlation between thyroid dysfunction and psychiatric symptoms exists but doesn't always imply direct causality 6

4. Neglecting to screen for comorbid conditions: Depression often co-occurs with anxiety, substance use disorders, and other psychiatric conditions that may require additional testing 1

By following this systematic laboratory approach, clinicians can better identify underlying medical conditions contributing to depressive symptoms, optimize treatment selection, and improve patient outcomes.