Can abrupt discontinuation of sertraline cause isolated ankle edema in a healthy 29‑year‑old woman?

Abrupt Sertraline Discontinuation and Ankle Edema

No, abrupt discontinuation of sertraline is extremely unlikely to cause isolated ankle edema in a healthy 29-year-old woman. This symptom does not fit the typical SSRI discontinuation syndrome profile and suggests an alternative etiology that requires investigation.

Why Sertraline Discontinuation Is Not the Cause

Expected Discontinuation Symptoms

When sertraline is stopped abruptly, the typical withdrawal syndrome manifests as:

• Central nervous system symptoms: dizziness, insomnia, fatigue, somnolence, headache, irritability, and anxiety 1
• Autonomic symptoms: sweating, nausea, and gastrointestinal disturbances 1
• Neurologic symptoms: paresthesias, tremors, and dysphoria 1

Peripheral edema is not a recognized feature of SSRI discontinuation syndrome 1.

Sertraline and Edema: The Actual Relationship

The relationship between sertraline and edema is paradoxical to your patient's presentation:

• Edema occurs during active sertraline use, not after discontinuation 2
• A 2023 systematic review of 45 cases found that peripheral edema associated with antidepressants (including sertraline) resolved following discontinuation of the medication, not after stopping it 2
• Among SSRIs, escitalopram was more commonly implicated in edema than sertraline; trazodone and mirtazapine were the most frequently associated antidepressants 2

Alternative Etiologies to Investigate

Most Likely Causes in a 29-Year-Old Woman

Evaluate for these specific conditions:

• Venous insufficiency or deep vein thrombosis: Check for unilateral vs bilateral presentation, calf tenderness, Homan's sign, and obtain venous duplex ultrasound if indicated 3
• Medication-induced edema from other drugs: Calcium channel blockers, NSAIDs, hormonal contraceptives, or corticosteroids 2
• Lymphedema: Look for thickened skinfold at the base of the second toe (Stemmer sign), non-pitting quality, and asymmetry 3
• Cardiac, renal, or hepatic dysfunction: Though less likely in a healthy 29-year-old, check BNP, creatinine, albumin, and liver function tests 3
• Inflammatory or rheumatologic conditions: Assess for morning stiffness, joint involvement, and obtain inflammatory markers (ESR, CRP, ANA) 3

Critical Diagnostic Steps

Perform these specific assessments:

1. Determine edema characteristics: Pitting vs non-pitting, unilateral vs bilateral, timing (worse at end of day suggests venous; constant suggests lymphatic) 3
2. Medication reconciliation: Identify any new medications started around the time of symptom onset, particularly those with known edema risk 2
3. Targeted laboratory evaluation: Complete metabolic panel, albumin, thyroid function, urinalysis for proteinuria 3
4. Imaging if indicated: Venous duplex for DVT concern, or lymphoscintigraphy if lymphedema suspected 3

Clinical Pitfall to Avoid

Do not attribute new symptoms to medication discontinuation without considering the expected syndrome profile. The timing coincidence of stopping sertraline and developing ankle edema is likely spurious rather than causal, as the pharmacologic mechanisms do not support this relationship 1, 2.