What baseline laboratory studies (complete blood count, comprehensive metabolic panel, thyroid‑stimulating hormone, pregnancy test, electrocardiogram for tricyclic antidepressants, fasting lipid panel, and lithium level with renal and thyroid function) should be obtained before initiating antidepressant therapy?

Baseline Laboratory Testing Before Initiating Antidepressants

For most antidepressants (SSRIs, SNRIs, and newer agents), no routine baseline laboratory testing is required in otherwise healthy adults. 1, 2

Medication-Specific Requirements

SSRIs and SNRIs (e.g., Fluoxetine, Duloxetine)

• No baseline labs needed for healthy adults on monotherapy 1
• Pregnancy test in females of childbearing age if clinically indicated 1
• Liver function tests (LFTs) only if pre-existing liver disease, HIV infection, or regular alcohol use 1
• Renal function (creatinine, BUN) only if considering future addition of lithium or other renally-cleared medications 1
• Duloxetine specifically does not require routine aminotransferase monitoring 3

Tricyclic Antidepressants (TCAs)

• Electrocardiogram (ECG) is essential before initiating TCAs to assess cardiac conduction and QTc interval 4, 5
• Complete blood count (CBC) and comprehensive metabolic panel (CMP) are reasonable given TCA toxicity risks 4
• TCAs have established therapeutic windows and require more careful baseline assessment due to cardiac and CNS toxicity potential 6

Lithium (for augmentation or bipolar depression)

• Serum creatinine and BUN (renal function) - mandatory 7
• Thyroid-stimulating hormone (TSH) - mandatory 7
• Baseline lithium level facilities must be available before initiating therapy 7
• Pregnancy test in females of childbearing age 7

Special Population Considerations

High-Risk Patients Requiring Additional Baseline Testing

• Elderly patients: Consider CBC, CMP, and TSH to rule out medical causes of depression 6
• Patients with diabetes: Continue standard diabetes monitoring; no additional antidepressant-specific testing 1
• Pre-existing liver disease: Obtain baseline LFTs before any antidepressant 1
• Cardiovascular disease: ECG recommended regardless of antidepressant class 8
• Children and adolescents: More comprehensive baseline assessment warranted due to different pharmacokinetics 6

What NOT to Order Routinely

Avoid these common pitfalls:

• Do not order routine "SSRI levels" or therapeutic drug monitoring at baseline - this is not cost-effective and provides no benefit 1
• Do not order routine liver enzymes for SSRIs/SNRIs in the absence of specific risk factors 3, 1
• Do not order fasting lipid panels unless prescribing atypical antipsychotics for augmentation 8
• Do not order CYP450 genotyping routinely at baseline - reserve for treatment failures or unusual responses 6

Algorithmic Approach to Baseline Testing

Step 1: Identify the antidepressant class

• SSRI/SNRI → Minimal to no labs
• TCA → ECG mandatory, consider CBC/CMP
• Lithium → Renal function, TSH, pregnancy test mandatory

Step 2: Screen for high-risk features

• Liver disease → Add LFTs
• Cardiac disease → Add ECG
• Childbearing potential → Add pregnancy test
• Elderly/pediatric → Consider CBC, CMP, TSH

Step 3: Document baseline only if monitoring will be needed

• Most SSRIs/SNRIs require no ongoing monitoring 3, 1
• TCAs may benefit from therapeutic drug monitoring during treatment 6, 5

Evidence Quality Note

The strongest evidence comes from recent clinical practice guidelines indicating that the historical practice of obtaining comprehensive baseline labs before antidepressants is not supported by outcomes data 3, 1, 2. The shift toward minimal baseline testing reflects recognition that routine monitoring does not improve morbidity, mortality, or quality of life for most patients on modern antidepressants 3, 1.