Can Vilazodone Cause Pain and Swelling in Feet?
Vilazodone is not documented to cause pain and swelling in the feet as a recognized adverse effect in the available medical literature. The most common side effects of vilazodone are gastrointestinal (diarrhea, nausea) and neurological (headache), with no established association with peripheral edema or foot pain 1, 2, 3.
Evidence Review
Known Adverse Effect Profile of Vilazodone
- The most frequently reported adverse effects of vilazodone include diarrhea, nausea, and headache, based on Phase III clinical trials 2, 3.
- Serious toxicity in overdose can include serotonin syndrome and seizures, particularly in children, but peripheral edema is not mentioned as a feature of vilazodone toxicity 1.
- Sexual dysfunction rates with vilazodone appear comparable to placebo, distinguishing it from traditional SSRIs 2.
Comparison to Related Antidepressants
- Peripheral edema is not a class effect of serotonin reuptake inhibitors or 5-HT1A partial agonists based on the vilazodone mechanism of action 2, 3.
- One case report documents peripheral edema (severe swelling of hands and feet) occurring with risperidone combined with citalopram (another serotonergic antidepressant), which resolved upon discontinuation and recurred upon rechallenge, implicating risperidone rather than the serotonergic agent 4.
Clinical Approach to Foot Pain and Swelling
Alternative Explanations to Consider
If a patient on vilazodone develops foot pain and swelling, investigate these more likely causes:
- Medication review for known culprits: Look for concurrent use of thiazolidinediones (which cause fluid retention in 3-5% as monotherapy), calcium channel blockers, NSAIDs, or corticosteroids 5.
- Cardiovascular assessment: Evaluate for new-onset heart failure, particularly if the patient has risk factors such as hypertension, prior myocardial infarction, or left ventricular hypertrophy 5.
- Venous insufficiency: Examine for signs of chronic venous disease, varicose veins, or dependent edema patterns 5.
- Renal function: Check serum creatinine and urinalysis for proteinuria suggesting nephrotic syndrome 5.
- Diabetic complications: If the patient has diabetes, assess for diabetic neuropathy (which causes pain) and peripheral arterial disease (which can cause both pain and swelling) 5.
Specific Physical Examination Findings
- Distinguish cardiac from non-cardiac edema: Check for jugular venous distention, S3 gallop, pulmonary rales, and orthopnea, which suggest heart failure rather than medication effect 5.
- Assess for inflammatory causes: Look for erythema, warmth, and tenderness suggesting cellulitis, gout (particularly affecting the great toe), or rheumatologic conditions 5.
- Neurological examination: Perform 10-g monofilament testing, pinprick, temperature, and vibration assessment to evaluate for diabetic neuropathy if applicable 5.
Management Recommendation
Do not discontinue vilazodone based solely on foot symptoms without identifying an alternative cause, as the temporal association may be coincidental rather than causal. Instead:
- Complete the diagnostic workup outlined above to identify the actual etiology 5.
- If no alternative cause is identified and symptoms are severe, consider a trial discontinuation of vilazodone with close monitoring to assess whether symptoms resolve 4.
- If symptoms resolve with discontinuation and recur with rechallenge, this would provide stronger evidence of causation (as demonstrated with risperidone in the case report) 4.
Common Pitfall to Avoid
Do not attribute every new symptom to the most recently started medication without considering the patient's complete medication list, comorbidities, and more common causes of the presenting complaint. Peripheral edema has multiple common etiologies that are far more likely than an undocumented adverse effect of vilazodone 5.