What is the treatment for orthostatic (postural) hypotension using Midodrine?

Midodrine for Orthostatic Hypotension

Midodrine is a first-line pharmacological treatment for symptomatic orthostatic hypotension when non-pharmacological measures are insufficient, with dosing of 2.5-10mg three times daily (first dose before arising and last dose at least 4 hours before bedtime). 1

Definition and Clinical Approach

Orthostatic hypotension (OH) is characterized by a decrease in blood pressure upon standing, associated with symptoms such as:

• Dizziness, lightheadedness, visual disturbances 1
• Weakness, fatigue, low energy 2, 3
• Near syncope or syncope 2, 3

Treatment Algorithm

Step 1: Non-pharmacological Measures (First-line)

• Identify and eliminate exacerbating factors:

  • Discontinue medications that worsen OH (psychotropic drugs, diuretics, α-adrenoreceptor antagonists) 1
  • Correct volume depletion 1

• Behavioral strategies:

  • Gradual staged movements with postural change 1
  • Physical counter-maneuvers (leg-crossing, stooping, squatting, tensing muscles) 1
  • Head-up bed position (10°) during sleep 1
  • Increased fluid (2-3L/day) and salt intake (10g NaCl/day) if not contraindicated 1
  • Rapid water ingestion 1
  • Avoidance of large carbohydrate-rich meals 1

• Compression garments:

  • Elastic garments over legs and abdomen 1
  • Should be at least thigh-high, preferably including abdomen 1

Step 2: Pharmacological Treatment (When symptoms persist despite non-pharmacological measures)

First-line Medications:

1. Midodrine:

   • Mechanism: Peripheral selective α1-adrenergic agonist that exerts pressor effect through arteriolar and venous constriction 1, 4
   • Dosing: 2.5-10 mg three times daily 1, 2
   • Administration timing: First dose before arising, last dose at least 4 hours before bedtime 1, 4
   • Efficacy: Increases standing systolic BP by 22 mmHg (28%) compared to placebo 2, 3
   • FDA approval status: Only medication FDA-approved specifically for symptomatic orthostatic hypotension 1, 4
   • Common adverse effects: Pilomotor reactions (13.5%), pruritus, paresthesias, urinary retention (4%), chills, supine hypertension (8%) 5, 3

2. Fludrocortisone:

   • Mechanism: Acts through sodium retention and direct constricting effect on partially denervated vessels 1
   • Dosing: Initial dose 0.05-0.1 mg daily, titrate to 0.1-0.3 mg daily 1
   • Adverse effects: Supine hypertension, hypokalemia, congestive heart failure, peripheral edema 1

Special Considerations

Monitoring and Precautions

• The goal is to minimize postural symptoms rather than restore normotension 1
• Balance between increasing standing BP and avoiding marked supine hypertension 1
• Midodrine can cause marked elevation of supine BP (>200 mmHg systolic) 4
• Continue midodrine only for patients who report significant symptomatic improvement 4

Treatment in Specific Populations

• In diabetic patients with orthostatic hypotension due to autonomic neuropathy:
  • Midodrine is effective at 5-10 mg doses 6
  • May be combined with fludrocortisone in non-responders to monotherapy 1

Additional Treatment Options

• Erythropoietin: For patients with hemoglobin <11 g/dL 1
• Desmopressin: For nocturnal polyuria and morning orthostatic hypotension 1
• Pyridostigmine: May benefit some patients 1
• Droxidopa: FDA-approved alternative for neurogenic OH 1

Pitfalls and Caveats

• Supine hypertension is a significant concern with midodrine therapy (up to 25% of patients) 5
• Avoid taking the final daily dose within 4 hours of bedtime to reduce risk of supine hypertension 5
• Midodrine should be used only in patients whose lives are considerably impaired despite standard clinical care 4
• Treatment should focus on symptom relief rather than normalizing blood pressure values 1
• Regular reassessment of treatment efficacy is essential 4