What are the treatment options for orthostatic hypotension?

Treatment of Orthostatic Hypotension

Initial Management: Identify and Eliminate Reversible Causes

The first and most critical step is to discontinue or switch medications that worsen orthostatic hypotension rather than simply reducing doses. 1

• Drug-induced autonomic failure is the most frequent cause of orthostatic hypotension, with diuretics and vasodilators being the most important culprits 1
• Alpha-1 blockers (doxazosin, prazosin, terazosin, tamsulosin) are strongly associated with orthostatic hypotension, especially in older adults 2
• Centrally-acting drugs (clonidine, methyldopa, guanfacine) and vasodilators (hydralazine, minoxidil) should be discontinued if possible 2
• For patients requiring continued antihypertensive therapy, switch to long-acting dihydropyridine calcium channel blockers or RAS inhibitors (ACE inhibitors/ARBs), which have minimal impact on orthostatic blood pressure 1, 2
• Evaluate for volume depletion, alcohol use, and endocrine disorders as reversible causes 1

Non-Pharmacological Interventions (First-Line for All Patients)

All patients should receive comprehensive non-pharmacological management before or alongside pharmacological treatment. 1

Fluid and Salt Management

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

Physical Countermeasures

• Teach leg crossing, squatting, stooping, and muscle tensing during symptomatic episodes—particularly effective in patients under 60 years with prodromal symptoms 1
• Implement gradual staged movements with postural changes 1

Compression Garments

• Use waist-high compression stockings (30-40 mmHg) and abdominal binders to reduce venous pooling 1

Positional and Dietary Modifications

• Elevate the head of bed by 10 degrees during sleep to prevent nocturnal polyuria, maintain favorable fluid distribution, and ameliorate nocturnal hypertension 1
• Eat smaller, more frequent meals to reduce post-prandial hypotension 1
• Encourage physical activity and exercise to avoid deconditioning, which worsens orthostatic intolerance 1

Pharmacological Treatment (When Non-Pharmacological Measures Fail)

The therapeutic goal is minimizing postural symptoms and improving functional capacity, not restoring normotension. 1

First-Line Pharmacological Options

Midodrine is the first-line pharmacological agent with the strongest evidence base, supported by three randomized placebo-controlled trials. 1, 3

• Midodrine (alpha-1 agonist): Start at 2.5-5 mg three times daily 1, 3

  • Increases standing systolic BP by 15-30 mmHg for 2-3 hours 1
  • Critical timing: Avoid the last dose after 6 PM (ideally at least 3-4 hours before bedtime) to prevent supine hypertension during sleep 1
  • FDA-approved for symptomatic orthostatic hypotension 3
  • Should only be continued in patients who report significant symptomatic improvement 3

• Fludrocortisone (mineralocorticoid): Start at 0.05-0.1 mg once daily, titrate to 0.1-0.3 mg daily (maximum 1.0 mg daily) 1

  • Works through sodium retention and vessel wall effects 1
  • Can be used as monotherapy or added to midodrine for non-responders 1
  • Contraindications: Active heart failure, significant cardiac dysfunction, severe renal disease, or pre-existing supine hypertension 1
  • Monitoring required: Check for supine hypertension (most important limiting factor), hypokalemia, congestive heart failure, and peripheral edema 1
  • Monitor electrolytes, BUN, and creatinine periodically 1

• Droxidopa: FDA-approved, particularly effective for neurogenic orthostatic hypotension in Parkinson's disease, pure autonomic failure, and multiple system atrophy 1

  • May reduce falls 1

Second-Line Options for Refractory Cases

• Pyridostigmine: Beneficial for refractory orthostatic hypotension in elderly patients who have not responded to other treatments 1

  • Favorable side effect profile compared to alternatives like fludrocortisone 1
  • Does not cause fluid retention or supine hypertension 2
  • Common side effects include nausea, vomiting, abdominal cramping, sweating, salivation, and urinary incontinence 1

• Combination therapy: Consider midodrine plus fludrocortisone for non-responders to monotherapy 1

Critical Monitoring Requirements

Measure blood pressure after 5 minutes of sitting/lying, then at 1 and 3 minutes after standing to document orthostatic changes. 1

• Monitor for supine hypertension development, which can cause end-organ damage 1
• Monitor orthostatic vital signs at each follow-up visit 1
• Reassess within 1-2 weeks after medication changes 1
• Check electrolytes periodically if using fludrocortisone due to mineralocorticoid effects causing potassium wasting 1

Special Populations

Patients with Concurrent Hypertension and Orthostatic Hypotension

• Test for orthostatic hypotension before starting or intensifying any blood pressure-lowering medication 1, 2
• Prefer long-acting dihydropyridine calcium channel blockers or RAS inhibitors as first-line agents 1, 2
• Switch medications that worsen orthostatic hypotension to alternatives rather than reducing doses 1, 2

Diabetic Patients

• Assess for cardiovascular autonomic neuropathy 1
• Consider alpha-lipoic acid for painful diabetic neuropathy, potentially beneficial for autonomic function 1

Common Pitfalls to Avoid

• Do not simply reduce the dose of offending medications—switch to alternatives 1
• Do not administer midodrine after 6 PM 1
• Do not use fludrocortisone in patients with heart failure or supine hypertension 1
• Do not combine multiple vasodilating agents (ACE inhibitors + calcium channel blockers + diuretics) without careful monitoring 1
• Do not overlook volume depletion as a contributing factor 1
• Do not inappropriately withhold ACE inhibitors from patients who would benefit (heart failure, post-MI, diabetes, chronic kidney disease) simply because they have orthostatic hypotension—instead, start at low doses and titrate gradually 2