What is the best treatment and lab workup for a patient with a Patient Health Questionnaire (PHQ-9) score of 20 and a Generalized Anxiety Disorder (GAD-7) score of 19 to rule out underlying physical causes of depression and anxiety?

Treatment and Laboratory Workup for Severe Depression and Anxiety

Immediate Clinical Assessment

This patient requires urgent psychiatric referral and initiation of pharmacotherapy with an SSRI, as a PHQ-9 score of 20 indicates severe depressive symptomatology and a GAD-7 score of 19 indicates severe anxiety. 1

Critical Safety Evaluation

• Immediately assess item 9 of the PHQ-9 regarding self-harm thoughts—any positive response warrants emergency risk assessment and potential referral for emergency evaluation. 1
• Patients identified as at risk of harm to self or others require immediate referral to appropriate emergency services. 1

Treatment Algorithm

Pharmacologic Management

• Initiate an SSRI such as sertraline 50 mg daily for combined treatment of both severe depression and severe anxiety, as SSRIs have demonstrated efficacy in treating generalized anxiety disorder and major depressive disorder. 1, 2
• Sertraline can be administered once daily, either morning or evening, with dose adjustments at intervals of at least 1 week given its 24-hour elimination half-life. 2
• Patients not responding to 50 mg/day may benefit from dose increases up to 200 mg/day. 2
• Common side effects to counsel about include nausea (25%), diarrhea (20%), insomnia (21%), dry mouth (14%), and somnolence (13%). 2

Psychiatric Referral

• Refer to psychiatry and/or psychology for diagnostic confirmation and ongoing management, as PHQ-9 scores ≥15 warrant specialist evaluation. 1
• The clinical team must determine when referral to a psychiatrist, psychologist, or equivalently trained professional is necessary as a shared responsibility. 3

Laboratory Workup to Rule Out Medical Causes

Before confirming a primary mood disorder diagnosis, rule out medical and substance-induced causes of depressive and anxiety symptoms. 1

Essential Laboratory Tests

The American Society of Clinical Oncology recommends evaluating for medical causes including: 1

• Thyroid function tests (TSH, free T4) to exclude thyroid disorders
• Complete metabolic panel to identify electrolyte imbalances that can cause mood symptoms
• Complete blood count to assess for anemia or infection
• Vitamin B12 and folate levels as deficiencies can mimic depression
• Liver function tests if considering medication initiation
• Toxicology screen to rule out substance use or withdrawal

Additional Clinical Considerations

• Assess for uncontrolled pain or fatigue, as these physical symptoms can manifest as depression. 1
• Evaluate for delirium from infection or metabolic derangement. 1
• Review all current medications for potential mood-altering side effects (e.g., interferon, corticosteroids, beta-blockers). 3, 1
• Screen for substance use or withdrawal states. 1

Monitoring and Follow-up

Treatment Response Assessment

• Reassess PHQ-9 and GAD-7 scores at regular intervals to monitor treatment response and adjust therapy accordingly. 1
• The goal is full functional recovery across work, social, and family domains—not just symptom remission. 1
• Maintain patients on the lowest effective dose with periodic reassessment to determine need for continued treatment. 2

Common Pitfalls to Avoid

• Do not fail to assess item 9 of the PHQ-9, as omitting the self-harm question may artificially lower scores and miss critical suicide risk. 1
• Do not overlook the high comorbidity between depression and anxiety—approximately 31% of patients with an anxiety disorder also have major depressive disorder. 1
• When multiple diagnoses are present, prioritize treatment for the condition causing the greatest functional impairment. 1
• Do not initiate antidepressant therapy without first ruling out medical causes, as treating a medication side effect or thyroid disorder with an SSRI will not address the underlying problem. 3, 1