Which medication, Viibryd (vilazodone) or Doxepin, is more likely to cause dizziness, especially in older adults?

Viibryd is More Likely to Cause Dizziness Than Doxepin, Especially in Older Adults

Based on FDA labeling and clinical trial data, Viibryd (vilazodone) demonstrates a significantly higher risk of dizziness compared to doxepin, particularly in vulnerable populations including older adults and pediatric patients.

Evidence from FDA Drug Labeling

Viibryd's Dizziness Profile

• Dizziness was reported in at least 5% of pediatric patients treated with Viibryd and occurred at a rate at least twice that of placebo, establishing it as a prominent adverse effect 1
• The FDA label specifically identifies dizziness as one of the most common adverse reactions requiring disclosure for Viibryd across age groups 1

Doxepin's Adverse Effect Profile

• Doxepin trials in older adults (n=494) over 4-12 weeks showed that adverse effects and study withdrawals did not significantly differ from placebo, indicating a favorable tolerability profile 2
• In comparative studies, doxepin's most common side effects were dry mouth, drowsiness/sedation, and constipation, with dizziness/lightheadedness being notably less prominent than with other antidepressants 3

Comparative Clinical Trial Data

Direct Comparison Evidence

• In a double-blind geriatric study comparing fluoxetine to doxepin, dizziness/lightheadedness was specifically listed as a common side effect of doxepin (p=0.005), but this was in the context of comparison to a drug with even fewer side effects 3, 4
• However, when doxepin was compared to placebo in insomnia trials, no significant differences in adverse effects were observed, suggesting the dizziness risk is lower than many assume 2

Dose-Dependent Considerations

• Low-dose doxepin (1-6 mg) used for insomnia in older adults showed no significant difference in adverse effects compared to placebo over 4-12 weeks 2
• Higher doses of doxepin (25-50 mg) have insufficient evidence regarding specific adverse effects, but historical data suggests increased anticholinergic burden 2

Special Considerations for Older Adults

Anticholinergic and Sedative Burden

• Doxepin demonstrates high anticholinergic activity (>15 pmol/mL atropine equivalents) at typical doses, which can contribute to confusion and falls rather than isolated dizziness 5
• Gabapentinoids, which are often co-prescribed, cause somnolence, dizziness, and mental clouding that are "very problematic in older patients" 2, but this is distinct from Viibryd's mechanism

Viibryd's Specific Risk Profile

• Serotonergic antidepressants like Viibryd have been associated with clinically significant hyponatremia in elderly patients, which can manifest as dizziness and increase fall risk 1
• The FDA label notes that elderly patients may be at greater risk for this adverse reaction, compounding the direct dizziness effect 1

Clinical Algorithm for Decision-Making

When choosing between these medications in older adults:

1. If the primary concern is dizziness and fall risk: Choose low-dose doxepin (1-6 mg) over Viibryd, as it has demonstrated no significant difference from placebo in adverse effects 2

2. If using standard antidepressant doses: Viibryd carries a higher documented risk of dizziness based on FDA labeling and pediatric trial data showing twice the placebo rate 1

3. Monitor for orthostatic hypotension: While doxepin historically causes less postural hypotension than other tricyclics 6, both medications require blood pressure monitoring in older adults

4. Consider anticholinergic burden: Doxepin's high anticholinergic activity may cause cognitive effects and falls through mechanisms other than pure dizziness 5

Critical Caveats

• The evidence for doxepin showing "no significant adverse effects" applies primarily to low doses (1-6 mg) used for insomnia, not standard antidepressant doses 2
• Viibryd's dizziness data comes from pediatric populations, but the FDA specifically lists it as occurring at twice the placebo rate, suggesting clinical significance 1
• Combination with other CNS depressants exponentially increases risk for both medications, particularly in elderly patients with COPD or respiratory compromise 7, 8