A 45-year-old man with a 2-month history of Major Depressive Disorder presents with persistent fatigue, weight loss, and poor concentration. His physician suspects underlying medical comorbidity. Which investigation is most appropriate as the next step before initiating antidepressant therapy?

## Screening for Medical Causes in Depression **Key Point:** Before diagnosing primary MDD, organic causes must be excluded. Thyroid dysfunction is the most common medical cause of depressive symptoms and must be screened. ### Rationale for TSH/Free T4 Screening 1. **Prevalence:** Hypothyroidism causes depression in ~5–10% of depressed patients 2. **Treatable:** Thyroid replacement resolves depression if primary cause 3. **Cost-effective:** Simple, non-invasive, inexpensive blood test 4. **High-yield:** Part of standard workup for depression ### Recommended Baseline Investigations for MDD | Investigation | Indication | Rationale | |---|---|---| | **TSH + Free T4** | All patients | Rule out hypothyroidism | | **Vitamin B12 + folate** | Fatigue, neuropsych symptoms | B12 deficiency causes depression | | **Fasting glucose / HbA1c** | Weight loss, metabolic risk | Diabetes screening | | **CBC** | Anemia screening | Anemia causes fatigue/depression | | **Renal function, LFTs** | Baseline before antidepressants | Safety assessment | **High-Yield:** TSH is the single most important screening test in depression workup. Hypothyroidism must be excluded before attributing symptoms to primary MDD. **Clinical Pearl:** Subclinical hypothyroidism (elevated TSH, normal free T4) may also contribute to depressive symptoms and warrants consideration for thyroid replacement.