What is the most appropriate initial investigation for a patient with depression, anxiety, loss of appetite, and social isolation, who is non-compliant with their antidepressant and anxiolytic medications and wants to use marijuana for stress relief?

Thyroid Function Test (TFT) is the Most Appropriate Initial Investigation

For a patient presenting with depression, loss of appetite, social isolation, medication non-compliance, and anxiety, thyroid function testing should be performed first to rule out thyroid dysfunction as an underlying medical cause of psychiatric symptoms. 1

Rationale for Thyroid Screening

Medical Causes Must Be Excluded First

• Depression and anxiety guidelines consistently emphasize treating medical causes of depressive symptoms before attributing symptoms to primary psychiatric disorders. 1
• Thyroid dysfunction (both hypothyroidism and hyperthyroidism) can present with depression, anxiety, appetite changes, and social withdrawal—mimicking primary psychiatric illness. 2
• The American Diabetes Association guidelines recommend screening for psychosocial/emotional disorders but emphasize that providers should "first, treat medical causes of depressive symptoms" before proceeding with psychiatric interventions. 1

Clinical Presentation Supports TFT Priority

• Loss of appetite, depression, and social isolation are classic presentations of thyroid dysfunction that must be excluded. 2
• Medication non-compliance in this context may reflect underlying cognitive impairment or apathy from undiagnosed thyroid disease rather than primary psychiatric pathology. 1
• A sensitive TSH assay is the recommended initial screening test when thyroid dysfunction probability exists, followed by free T4 if TSH is abnormal. 2

Why Other Options Are Less Appropriate Initially

Urine Drug Test (Option B)

• While the patient expresses intent to use marijuana, there is no indication of current substance use requiring immediate toxicology screening. 3
• Cannabis use for anxiety is increasingly common, but evidence shows THC can be anxiogenic at higher doses, while CBD may have anxiolytic properties—making this a complex therapeutic consideration rather than a diagnostic priority. 4, 5
• Drug screening becomes relevant after medical causes are excluded and if substance use disorder is suspected, but it does not address the underlying medical evaluation needed first. 3

Complete Blood Count (Option A)

• While CBC can identify anemia contributing to fatigue and depression, it is less likely to explain the constellation of psychiatric symptoms, appetite loss, and social withdrawal compared to thyroid dysfunction. 1
• CBC would be appropriate as part of a comprehensive workup but not as the single most important initial investigation. 1

Pulmonary Function Test (Option C)

• There is no indication of respiratory symptoms, dyspnea, or chronic lung disease in this presentation. 1
• PFTs are indicated when respiratory disease contributes to anxiety and depression (such as in COPD), but this patient has no respiratory complaints. 1

Clinical Algorithm After TFT

If Thyroid Function is Abnormal

• Treat the thyroid disorder appropriately, as this may resolve or significantly improve psychiatric symptoms. 2
• Reassess psychiatric symptoms after thyroid normalization before initiating psychotropic medications. 1

If Thyroid Function is Normal

• Proceed with formal depression and anxiety screening using validated instruments (PHQ-9 for depression, GAD-7 for anxiety). 1
• The American Society of Clinical Oncology and diabetes guidelines recommend screening at initial visits and with disease/treatment changes using validated measures with established cutoffs. 1
• Address medication non-compliance through patient education, assessment of barriers, and consideration of simplified regimens. 1
• Consider urine drug screening if substance use history or current use is suspected after initial medical evaluation. 3

Critical Pitfall to Avoid

Do not prematurely diagnose primary psychiatric illness without excluding medical causes, particularly thyroid dysfunction, which can fully explain this symptom constellation and is readily treatable. 1 Initiating antidepressants or anxiolytics without addressing underlying thyroid disease will result in treatment failure and delayed appropriate care. 2