## Rationale for Therapeutic Drug Monitoring in SSRI Non-Response **Key Point:** Therapeutic drug monitoring (TDM) of SSRIs is indicated when there is inadequate clinical response despite adequate dosing and duration (≥4 weeks at therapeutic dose). Sertraline levels help distinguish true non-response from poor compliance or subtherapeutic exposure due to rapid metabolism or drug–drug interactions. ### Why TDM is the Investigation of Choice 1. **Confirms drug exposure**: Serum sertraline level determines whether the patient has achieved therapeutic concentration (typically 50–200 ng/mL for sertraline). 2. **Guides clinical decision**: Low levels suggest non-compliance, malabsorption, or rapid metabolism → increase dose or check adherence. Therapeutic or high levels suggest true pharmacological non-response → consider switching class. 3. **Prevents unnecessary polypharmacy**: Avoids premature augmentation or switching without confirming adequate drug delivery. 4. **Cost-effective**: Cheaper and faster than empirical drug switching. **High-Yield:** SSRI TDM is particularly useful in cases of suspected poor metabolism (e.g., CYP2D6 poor metabolizers) or drug interactions that reduce sertraline bioavailability. ### Timeline Context - Week 3 of therapy: Still within the response window (SSRIs typically show benefit by week 4–6), but TDM at this point helps rule out exposure issues early. - Adequate dosing duration: 50 mg daily is a standard starting dose; 3 weeks allows time for steady-state (sertraline t½ ≈ 26 hours, steady-state by day 5–7). **Clinical Pearl:** In Indian practice, TDM is underutilized but increasingly recognized as cost-effective for guiding antidepressant optimization, especially in patients with multiple comorbidities or polypharmacy. [cite:KD Tripathi 8e Ch 12]
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