What initial laboratory tests and treatments are recommended for patients presenting with depression?

Initial Laboratory Testing and Treatment for Depression

For patients presenting with depression, routine laboratory testing beyond thyroid function studies is not supported by evidence, and initial treatment should focus on validated screening with the PHQ-9 followed by either antidepressant medication or specific psychotherapy based on symptom severity. 1

Laboratory Testing Recommendations

Thyroid Function Testing

• Thyroid function studies (TSH) should be obtained as part of the baseline assessment to rule out thyroid-induced depressive symptoms, though overt thyroid disease is rare among depressed patients (0.4% hyperthyroidism, 0% overt hypothyroidism in one study). 2, 3
• Subclinical thyroid dysfunction is not associated with prevalent or incident depression in older adults, and routine screening for subclinical thyroid disease does not appear to affect depression outcomes. 4

Additional Baseline Laboratory Work

• Complete blood counts, liver function tests, and metabolic panels should be obtained at baseline before initiating treatment, particularly for patients who will receive antidepressant medications. 2
• These tests help identify medical conditions that may contribute to depressive symptoms and establish baseline values for monitoring treatment-related adverse effects. 2

What NOT to Routinely Order

• There is no evidence supporting routine screening beyond thyroid function and basic metabolic assessment in the absence of specific clinical indicators. 3, 4
• Additional testing should be guided by clinical presentation, risk factors, and suspected comorbid conditions (substance use, medical illness). 2

Depression Screening and Assessment

Initial Screening Approach

• Use the PHQ-9 as the primary screening tool, which has sensitivity of 89.5% and specificity of 77.5% at a cutoff score of ≥11 for detecting major depressive disorder. 1
• A two-step approach can be used: start with PHQ-2 (first two questions about depressed mood and anhedonia); if positive (score ≥2), complete the full PHQ-9. 2, 1
• The recommended cutoff score is ≥8 based on studies in specific populations, though the traditional cutoff is ≥10. 2, 1

Comprehensive Assessment Requirements

• All positive screens require direct clinical interview using DSM-5 criteria to confirm diagnosis—screening alone does not establish a diagnosis. 2
• Assess for suicidal ideation (PHQ-9 item 9), bipolar disorder risk, psychotic symptoms, substance use, and comorbid anxiety disorders. 2, 5
• Evaluate functional impairment across multiple domains (work, relationships, self-care). 2
• Obtain collateral information from family members when possible. 2

Treatment Algorithm Based on PHQ-9 Score

Mild Symptoms (PHQ-9: 1-7)

• Provide education about depression and normal stress responses. 1
• Ensure adequate coping skills and access to resources. 1
• Consider reassessment at future visits, particularly for patients with risk factors. 1

Moderate Symptoms (PHQ-9: 8-14)

• Evaluate for pertinent history and specific risk factors (family history, previous episodes, trauma, psychosocial stressors). 2, 1
• Offer first-line treatment with either antidepressant medication OR specific psychotherapy. 6
• Consider referral to psychology or psychiatry for diagnostic evaluation and treatment initiation. 1

Moderate-to-Severe/Severe Symptoms (PHQ-9: 15-27)

• Make immediate referral to psychology and/or psychiatry for diagnosis and treatment. 1
• Assess for risk of harm to self or others immediately—any endorsement of specific plans or intent requires emergency intervention. 2, 1
• Evaluate for medical or substance-induced causes of depressive symptoms. 1
• Combined medication and psychotherapy is preferred for severe depression (standardized mean difference 0.30 vs psychotherapy alone, 0.33 vs medication alone). 6

First-Line Treatment Options

Antidepressant Medications

• All 21 studied antidepressants show efficacy over placebo with small-to-medium effect sizes (SMD 0.23 for fluoxetine to 0.48 for amitriptyline). 6
• Second-generation antidepressants (SSRIs, SNRIs, atypical agents) are first-line pharmacotherapy. 7
• Selection should consider treatment history, comorbidities, cost, and adverse effect profile. 7
• Screen all patients for bipolar disorder risk before initiating antidepressants to avoid precipitating manic episodes. 5

Psychotherapy Options

• Effective psychotherapies include cognitive therapy, behavioral activation, problem-solving therapy, interpersonal therapy, brief psychodynamic therapy, and mindfulness-based psychotherapy, all with medium-to-large effect sizes (SMD 0.50-0.73). 6
• Psychotherapy is as effective as medication for major depression but more time-intensive. 2

Combined Treatment

• Combination therapy (medication + psychotherapy) produces greater symptom improvement than either alone and should be considered for severe or chronic depression. 6

Critical Safety Monitoring

Suicidality Risk

• All patients on antidepressants require close monitoring for clinical worsening, suicidality, and unusual behavioral changes, especially during the first few months and with dose changes. 5
• Risk is highest in patients under age 25 (14 additional cases per 1000 treated vs placebo). 5
• Prescribe smallest quantity consistent with good management to reduce overdose risk. 5

Serotonin Syndrome

• Monitor for serotonin syndrome when combining antidepressants with other serotonergic drugs (triptans, tramadol, fentanyl, lithium, St. John's Wort). 5, 8
• Symptoms include mental status changes, autonomic instability, neuromuscular symptoms, and GI disturbances—requires immediate discontinuation and supportive care. 5

Other Monitoring

• Obtain laboratory tests before each medication adjustment and monitor for hyponatremia (especially in elderly), liver function changes, and metabolic effects. 2, 8
• Assess for angle-closure glaucoma risk, particularly with medications that have anticholinergic properties. 8

Common Pitfalls to Avoid

• Do not rely on screening scores alone for diagnosis—false-positive rates are 60-76% in primary care settings with 5-10% depression prevalence. 2
• Do not abruptly discontinue antidepressants—taper gradually while providing cognitive behavioral therapy to reduce relapse risk. 5, 8, 7
• Do not overlook comorbid conditions (anxiety, substance use, PTSD) that affect treatment selection and outcomes. 2
• Do not assume treatment response without systematic follow-up—collaborative care with regular outcome assessment significantly improves effectiveness (SMD 0.42). 6