What is the indication for midodrine (orthostatic hypotension treatment)?

Indications for Midodrine

Midodrine is primarily indicated for the treatment of symptomatic orthostatic hypotension in patients whose lives are considerably impaired despite standard clinical care, including non-pharmacological treatments. 1

Primary Indication

Midodrine is FDA-approved specifically for:

• Treatment of symptomatic orthostatic hypotension (OH)
• For patients who have failed standard clinical care including:
  • Support stockings/compression garments
  • Fluid expansion
  • Lifestyle alterations

Mechanism and Efficacy

Midodrine works through its active metabolite desglymidodrine, which:

• Acts as an alpha-1 adrenergic agonist
• Increases vascular tone in arteriolar and venous vasculature
• Elevates blood pressure, particularly standing systolic pressure
• Typically increases standing systolic blood pressure by 15-30 mmHg within 1 hour of a 10 mg dose 1
• Does not stimulate cardiac beta-adrenergic receptors
• Diffuses poorly across the blood-brain barrier (minimal CNS effects)

Clinical Evidence Supporting Use

Clinical trials have demonstrated that midodrine:

• Significantly improves 1-minute standing systolic blood pressure compared to placebo 2
• Increases standing time in patients with neurogenic orthostatic hypotension 3
• Improves symptoms including dizziness, lightheadedness, and syncope 2
• Provides approximately 521 seconds longer time to syncopal symptoms during tilt-table testing compared to placebo 4

Specific Clinical Scenarios

Midodrine is particularly useful in:

1. Neurogenic orthostatic hypotension - Class I recommendation 5
2. Diabetic cardiovascular autonomic neuropathy with symptomatic OH 5
3. Intradialytic hypotension - Administered 30 minutes before dialysis sessions 5

Dosing Considerations

• Typical dosing: 10 mg three times daily 1, 3
• Last dose should be taken at least 4 hours before bedtime to minimize supine hypertension 6
• In hemodialysis patients: 5 mg administered 30 minutes before dialysis 5
• Midodrine is removed by hemodialysis and its half-life is reduced to 1.4 hours during dialysis 5

Precautions and Monitoring

• Supine hypertension risk: Can cause marked elevation of supine blood pressure (>200 mmHg systolic) 1
• Monitor for bradycardia due to reflex parasympathetic stimulation 5
• Use cautiously in patients with:
  • Congestive heart failure
  • Patients taking negative chronotropic agents (beta-blockers, digoxin, non-dihydropyridine CCBs) 5
• Avoid concomitant use with other alpha-adrenergic agents (ephedrine, pseudoephedrine) 5
• May antagonize alpha-adrenergic blockers (terazosin, prazosin, doxazosin) 5

Common Side Effects

• Piloerection (goosebumps)
• Scalp itching or tingling
• Urinary retention
• Paresthesias
• Chills
• Nausea and heartburn 1, 6

Treatment Algorithm

1. First-line: Non-pharmacological measures (compression garments, increased fluid/salt intake, physical counter-pressure maneuvers) 5
2. Second-line: Midodrine (10 mg three times daily) 5
3. For inadequate response: Combination therapy with fludrocortisone 5
4. Alternative options: Droxidopa for neurogenic OH 5

Midodrine should be continued only in patients who report significant symptomatic improvement, as clinical benefits are measured primarily through improved ability to perform life activities rather than just blood pressure measurements 1.