What are the treatment options for orthostatic hypotension?

Treatment of Orthostatic Hypotension

Start with non-pharmacological interventions first, and only add medications when symptoms remain significantly disabling despite these measures, prioritizing midodrine or fludrocortisone as first-line agents. 1

Initial Management: Identify and Remove Culprits

• Discontinue or switch medications that worsen orthostatic hypotension rather than simply reducing doses 1
• Drug-induced autonomic failure is the most frequent cause, with diuretics, vasodilators, alpha-1 blockers (doxazosin, prazosin, terazosin), and centrally-acting agents (clonidine, methyldopa) being the primary culprits 1, 2
• Evaluate for reversible causes including volume depletion, alcohol use, endocrine disorders, and cardiovascular conditions 1

Non-Pharmacological Interventions (Implement for ALL Patients)

Volume Expansion Strategies

• Increase fluid intake to 2-3 liters daily 1
• Increase salt consumption to 6-9 grams daily (if not contraindicated by heart failure or renal disease) 1
• Acute water ingestion of ≥480 mL provides temporary relief with peak effect at 30 minutes 1

Postural and Physical Maneuvers

• Teach gradual staged movements with postural changes—avoid rapid standing 1
• Implement physical counter-maneuvers during symptom onset: leg crossing, squatting, stooping, and muscle tensing 1
• Elevate the head of bed by 10 degrees during sleep to prevent nocturnal polyuria and supine hypertension 1

Compression and Dietary Modifications

• Use compression garments including thigh-high stockings and abdominal binders to reduce venous pooling 1
• Eat smaller, more frequent meals to reduce post-prandial hypotension 1
• Encourage physical activity and exercise to avoid deconditioning 1

Pharmacological Treatment (When Non-Pharmacological Measures Fail)

First-Line Medications

Midodrine (Alpha-1 Agonist)

• Start at 2.5-5 mg three times daily, increases standing systolic BP by 15-30 mmHg for 2-3 hours 1, 3
• FDA-approved for symptomatic orthostatic hypotension 3
• Avoid the last dose after 6 PM to prevent supine hypertension during sleep 1
• Peak effect occurs 1 hour after dosing with duration of 2-3 hours 3

Fludrocortisone (Mineralocorticoid)

• Start at 0.05-0.1 mg daily, titrate individually to 0.1-0.3 mg daily (maximum 1.0 mg daily) 1
• Works through sodium retention and vessel wall effects, increasing plasma volume 1
• Monitor for supine hypertension (most important limiting factor), hypokalemia, congestive heart failure, and peripheral edema 1
• Contraindicated in active heart failure, significant cardiac dysfunction, severe renal disease, and pre-existing supine hypertension 1
• Evidence quality is limited with only very low-certainty evidence from small trials 1

Droxidopa

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

Combination Therapy

• For non-responders to monotherapy, combine midodrine and fludrocortisone 1

Second-Line and 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—does not cause fluid retention or supine hypertension 1, 2
• Common side effects include nausea, vomiting, abdominal cramping, sweating, salivation, and urinary incontinence 1

Other Agents for Specific Situations

• Erythropoietin for patients with anemia and severe autonomic neuropathy 1
• Desmopressin acetate for nocturnal polyuria and morning orthostatic hypotension 1

Treatment Goals and Monitoring

• The therapeutic goal is minimizing postural symptoms, NOT restoring normotension 1
• Measure blood pressure after 5 minutes lying/sitting, then at 1 and 3 minutes after standing to document orthostatic changes 1
• Balance the benefits of increasing standing BP against the risk of worsening supine hypertension 1
• Monitor regularly for supine hypertension with pressor agents and electrolyte abnormalities with fludrocortisone 1
• Reassess within 1-2 weeks after medication changes 1
• Continue midodrine only for patients who report significant symptomatic improvement 3

Special Considerations for Patients with Concurrent Hypertension

• Long-acting dihydropyridine calcium channel blockers or RAS inhibitors (ACE inhibitors/ARBs) are preferred first-line agents 1, 2
• Test for orthostatic hypotension before starting or intensifying any blood pressure-lowering medication 2
• Avoid beta-blockers unless there are compelling indications 2
• Switch medications that worsen orthostatic hypotension to alternatives rather than reducing doses 1

Critical Pitfalls to Avoid

• Do not aim for normotension—this will cause dangerous supine hypertension 1
• Avoid taking midodrine after 6 PM 1
• Do not use fludrocortisone in patients with heart failure or supine hypertension 1
• Recognize that fludrocortisone's plasma volume expansion effects are transient 4
• In patients with supine hypertension, avoiding the supine posture may be as important as increasing dietary salt 4