What are the recommended medications for treating reflex syncope?

Medication Treatment for Reflex Syncope

Most pharmacological treatments have limited efficacy for reflex syncope, and non-pharmacological approaches should be prioritized as first-line therapy. 1

First-Line Approach: Non-Pharmacological Measures

• Patient education and reassurance about the benign nature of the condition
• Physical counterpressure maneuvers (PCMs) such as leg crossing, muscle tensing, and squatting
  • These have been proven effective in a multicentre prospective trial with 39% relative risk reduction 1
• Increased fluid intake (2-3 liters daily) and salt intake (10g NaCl)
• Avoidance of triggering situations and prolonged standing

Pharmacological Options

Alpha-Agonists

• Midodrine (5-20mg three times daily)

  • May be useful in selected patients with frequent hypotensive symptoms
  • Evidence from small, open-label randomized trials shows some benefit 1
  • Consider as "pill in the pocket" strategy (single dose 1 hour before triggering activities)
  • Cautions:
    • Frequent dosing limits long-term compliance
    • Avoid in older males due to urinary outflow adverse effects
    • Not available in all European countries

• Etilefrine

  • Not recommended - randomized placebo-controlled trial showed no difference in frequency or time to recurrent syncope 1

Mineralocorticoids

• Fludrocortisone (0.1-0.3mg once daily)
  • Widely used in adults but lacks strong trial evidence for reflex syncope 1
  • More evidence supports its use in orthostatic hypotension 2
  • Caution: Monitor for electrolyte imbalances and supine hypertension

Beta-Blockers

• Not recommended for reflex syncope
  • Failed to show efficacy in five of six long-term follow-up studies 1
  • May worsen bradycardia in carotid sinus syndrome

Other Medications

• Paroxetine

  • Shown effective in one placebo-controlled trial from a single institution
  • Not confirmed by other studies 1
  • Caution: Psychotropic drug requiring careful consideration in patients without psychiatric disease

• Droxidopa (100-600mg three times daily)

  • May have short-term effects on improving symptoms in orthostatic hypotension 3
  • Limited evidence for reflex syncope specifically

Special Considerations

Cardiac Pacing

• Limited role in reflex syncope therapy
• Consider only when severe spontaneous bradycardia is documented during prolonged monitoring 1
• Most effective in cardioinhibitory type with documented asystole during spontaneous events

Algorithm for Treatment Selection

1. Start with non-pharmacological measures (education, PCMs, fluid/salt intake)
2. If symptoms persist despite non-pharmacological measures:
   • For patients with clear prodromal symptoms: Consider midodrine as "pill in the pocket"
   • For patients with documented bradycardia/asystole: Consider cardiac pacing evaluation
   • For patients with orthostatic component: Consider fludrocortisone or midodrine

Common Pitfalls

• Overreliance on medications when non-pharmacological approaches are more effective
• Using beta-blockers despite evidence against their efficacy
• Failing to teach physical counterpressure maneuvers, which have strong evidence
• Inadequate fluid and salt intake recommendations
• Not monitoring for supine hypertension with vasopressor medications

Monitoring Recommendations

• Track symptom frequency and severity with a diary
• Monitor blood pressure in both supine and standing positions
• For patients on fludrocortisone: Regular electrolyte monitoring
• For patients on midodrine: Monitor for urinary retention in older males

Remember that the placebo effect is significant in reflex syncope treatment, which underscores the importance of evaluating any treatment in randomized controlled trials 4.