What is the drug of choice for treating orthostatic (postural) hypotension?

First-Line Drug Treatment for Orthostatic Hypotension

Midodrine is the drug of choice for treating orthostatic hypotension, particularly when non-pharmacological measures have failed to adequately control symptoms. 1, 2

Treatment Algorithm

1. Non-pharmacological approaches (first-line)

   • Increase fluid intake to 2-3 liters daily and salt consumption to 6-9g daily (if not contraindicated) 1
   • Implement physical counter-maneuvers (leg crossing, muscle tensing, squatting) 1
   • Use compression garments (thigh-high and abdominal) 1
   • Elevate head of bed during sleep (10°) 1
   • Consume smaller, more frequent meals to reduce post-prandial hypotension 1
   • Maintain physical activity to avoid deconditioning 1

2. Pharmacological treatment (when non-pharmacological measures fail)

   • First-line medications:

     • Midodrine: Alpha-1 agonist, FDA-approved, initial dose 2.5-5mg three times daily 1, 2
     • Fludrocortisone: Mineralocorticoid, initial dose 0.05-0.1mg daily 1
     • Droxidopa: FDA-approved for neurogenic orthostatic hypotension 1

   • Second-line/adjunctive options:

     • Pyridostigmine: For refractory cases, fewer side effects than alternatives 1
     • Erythropoietin: For patients with anemia and severe autonomic neuropathy 1
     • Desmopressin: May correct nocturnal polyuria and morning orthostatic hypotension 1

Evidence Supporting Midodrine as First Choice

Midodrine has strong evidence supporting its use as the drug of choice:

• FDA-approved specifically for symptomatic orthostatic hypotension 2
• Increases standing systolic BP by 15-30 mmHg for 2-3 hours 1
• Demonstrated efficacy in randomized controlled trials showing significant improvement in standing BP and orthostatic symptoms 3
• Comparative studies show midodrine to be at least as effective as other sympathomimetic agents and dihydroergotamine 4, 5
• Well-tolerated with manageable side effects 4

Important Considerations and Precautions

• Timing of doses: Avoid taking the last dose of midodrine after 6 PM to prevent supine hypertension during sleep 1
• Monitoring: Regular assessment for supine hypertension is essential (can cause BP>200 mmHg systolic) 2
• Common side effects: Piloerection, pruritus, paresthesias, urinary retention, and chills 4
• Contraindications: Severe cardiac disease, acute renal disease, urinary retention, pheochromocytoma, thyrotoxicosis 5
• Continued use: After initiation, midodrine should be continued only for patients who report significant symptomatic improvement 2

Special Populations

• Patients with both hypertension and orthostatic hypotension:

  • Consider long-acting dihydropyridine calcium channel blockers or RAS inhibitors as first-line antihypertensive therapy 1, 6
  • Avoid beta-blockers unless there are compelling indications 6

• Diabetic patients:

  • Assess for cardiovascular autonomic neuropathy 1
  • Consider α-lipoic acid for painful diabetic neuropathy 1
  • Pyridostigmine may benefit diabetic patients as it doesn't cause fluid retention or supine hypertension 6

Combination Therapy

For non-responders to monotherapy, consider combination therapy with midodrine and fludrocortisone 1, 7

Treatment Goals

The therapeutic goal should be minimizing postural symptoms rather than restoring normotension 1