What is the best treatment for orthostatic (postural) hypotension?

Treatment of Orthostatic Hypotension

Stepwise Treatment Algorithm

Begin with non-pharmacologic interventions for all patients, and add pharmacologic therapy only when symptoms persist despite these measures, with midodrine as the first-line medication due to its strongest evidence base. 1

Step 1: Identify and Eliminate Reversible Causes

• Discontinue or switch offending medications immediately rather than simply reducing doses, as drug-induced autonomic failure is the most frequent cause of orthostatic hypotension 1, 2
• High-risk medications to discontinue include:
  • Alpha-1 blockers (doxazosin, prazosin, terazosin, tamsulosin) 2
  • Diuretics, particularly thiazides in elderly patients 2
  • Centrally-acting antihypertensives (clonidine, methyldopa) 2
  • Vasodilators (hydralazine, minoxidil) 2
• If antihypertensive therapy must continue, switch to long-acting dihydropyridine calcium channel blockers or RAS inhibitors, which have minimal impact on orthostatic blood pressure 2
• Assess for volume depletion, alcohol use, and endocrine disorders 1

Step 2: Implement Non-Pharmacologic Interventions (All Patients)

Fluid and salt management:

• Increase fluid intake to 2-3 liters daily 1
• Increase salt intake to 6-9 grams daily (unless contraindicated by heart failure) 1
• Acute water ingestion of ≥480 mL provides temporary relief with peak effect at 30 minutes 1

Physical countermeasures during symptomatic episodes:

• Teach leg crossing, squatting, stooping, and muscle tensing—particularly effective in patients under 60 years with prodromal symptoms 1
• These maneuvers increase venous return and can abort symptoms before syncope occurs 1

Compression therapy:

• Use waist-high compression stockings (30-40 mmHg) and abdominal binders to reduce venous pooling 1
• Thigh-high compression alone is less effective than abdominal compression 1

Postural modifications:

• Elevate head of bed by 10 degrees during sleep to prevent nocturnal polyuria, maintain favorable fluid distribution, and ameliorate nocturnal hypertension 1
• Teach gradual staged movements with postural changes 1
• Avoid taking the last medication dose after 6 PM to prevent supine hypertension 1

Dietary modifications:

• Eat smaller, more frequent meals to reduce post-prandial hypotension 1
• Encourage physical activity and exercise to avoid deconditioning 1

Step 3: First-Line Pharmacologic Therapy

Midodrine is the first-line medication with the strongest evidence base (three randomized placebo-controlled trials demonstrating efficacy) 1, 3:

• Start at 2.5-5 mg three times daily 1
• Titrate individually up to 10 mg three times daily based on response 1
• Critical timing: Last dose must be taken at least 3-4 hours before bedtime (not after 6 PM) to prevent supine hypertension during sleep 1, 3
• Increases standing systolic BP by 15-30 mmHg for 2-3 hours 1
• Monitor for supine hypertension, bradycardia, and urinary retention 3
• Avoid concomitant use with other vasoconstrictors, cardiac glycosides, or beta-blockers without careful monitoring 3

Step 4: Second-Line or Combination Therapy

If midodrine alone provides insufficient symptom control, add fludrocortisone:

• Start at 0.05-0.1 mg once daily 1
• Titrate to 0.1-0.3 mg daily (maximum 1.0 mg daily) 1
• Acts through sodium retention and vessel wall effects—complementary mechanism to midodrine's alpha-1 adrenergic stimulation 1
• Monitor closely for:
  • Supine hypertension (most important limiting factor) 1
  • Hypokalemia (check electrolytes periodically) 1
  • Congestive heart failure and peripheral edema 1
• Contraindications: Active heart failure, significant cardiac dysfunction, severe renal disease, pre-existing supine hypertension 1

Alternative first-line agents:

• Droxidopa: FDA-approved, particularly effective for neurogenic orthostatic hypotension in Parkinson's disease, pure autonomic failure, and multiple system atrophy; may reduce falls 1, 3
• Pyridostigmine: Consider for refractory cases, especially in elderly patients; favorable side effect profile with no fluid retention or supine hypertension 1

Step 5: Monitoring and Treatment Goals

The therapeutic objective is minimizing postural symptoms and improving functional capacity, NOT restoring normotension 1:

• Measure BP after 5 minutes lying/sitting, then at 1 and 3 minutes after standing to document orthostatic changes 1
• Reassess within 1-2 weeks after medication changes 1
• Monitor orthostatic vital signs at each follow-up visit 1
• Balance the benefits of increasing standing BP against the risk of worsening supine hypertension 1

Critical Pitfalls to Avoid

• Never simply reduce the dose of offending medications—switch to alternatives instead 1, 2
• Never administer midodrine after 6 PM due to supine hypertension risk 1
• Never use fludrocortisone in patients with heart failure or supine hypertension 1
• Never combine multiple vasodilating agents (ACE inhibitors + calcium channel blockers + diuretics) without careful monitoring 1
• Never overlook volume depletion as a contributing factor 1
• Never use beta-blockers in patients with orthostatic hypotension unless there are compelling indications 2

Special Populations

Patients with both hypertension and orthostatic hypotension:

• Test for orthostatic hypotension before starting or intensifying any BP-lowering medication 2
• Prefer long-acting dihydropyridine calcium channel blockers or RAS inhibitors as first-line agents 2
• Avoid diuretics and alpha-blockers 2

Diabetic patients:

• Assess for cardiovascular autonomic neuropathy 1
• Consider alpha-lipoic acid for painful diabetic neuropathy with potential autonomic benefits 1

Elderly or frail patients (≥85 years):

• Long-acting dihydropyridine CCBs or RAS inhibitors are preferred first-line agents if antihypertensive therapy is needed 2
• Thiazide diuretics often cause orthostatic hypotension and further reduction in renal function in this population 2