What is the recommended management for orthostatic hypotension, including non‑pharmacologic and pharmacologic options?

Management of Orthostatic Hypotension

Diagnostic Confirmation

Measure blood pressure after 5 minutes of supine or seated rest, then at both 1 minute and 3 minutes after standing, keeping the arm supported at heart level throughout. 1, 2 Orthostatic hypotension is confirmed by a drop of ≥20 mmHg systolic or ≥10 mmHg diastolic (or systolic falling below 90 mmHg) within 3 minutes of standing. 1, 3

• Document heart rate response during postural change: a blunted increase (<10 bpm) suggests neurogenic orthostatic hypotension, whereas a compensatory tachycardia (>15 bpm) indicates non-neurogenic causes. 3
• Assess for accompanying symptoms—dizziness, lightheadedness, visual blurring, syncope—to correlate hemodynamic findings with clinical presentation. 1
• Evaluate for reversible causes: volume depletion (dehydration, blood loss), medication effects, endocrine disorders (adrenal insufficiency), and cardiac dysfunction before attributing symptoms to autonomic failure. 1, 3

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Medication Review and Discontinuation (First Priority)

Discontinue or switch—do not simply reduce the dose—medications that worsen orthostatic hypotension, as drug-induced autonomic failure is the most frequent cause. 1, 3

High-Risk Medications to Discontinue:

• Alpha-1 blockers (doxazosin, prazosin, terazosin, tamsulosin) are the most problematic agents and should be stopped immediately. 1
• Centrally acting antihypertensives (clonidine, methyldopa, guanfacine) must be tapered gradually over 1–2 weeks to avoid rebound hypertension, then switched to alternative therapy. 1
• Diuretics and vasodilators (hydralazine, nitrates) should be discontinued or switched to agents with minimal orthostatic impact. 1, 3
• Beta-blockers should be avoided unless compelling indications exist (heart failure, recent MI), as they can exacerbate orthostatic hypotension. 1

Preferred Antihypertensive Alternatives (if BP control needed):

• Long-acting dihydropyridine calcium channel blockers (amlodipine) or RAS inhibitors (ACE inhibitors/ARBs) are first-line agents for patients with concurrent hypertension and orthostatic hypotension. 1, 3 These agents minimize orthostatic effects while providing cardiovascular protection.

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Non-Pharmacologic Management (Foundational Measures)

All patients should implement non-pharmacologic interventions before or alongside pharmacologic therapy, as these measures form the cornerstone of treatment. 1, 3

Volume Expansion:

• Increase fluid intake to 2–3 liters daily and dietary sodium to 6–9 grams daily, unless contraindicated by heart failure or uncontrolled hypertension. 1, 3
• 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—these maneuvers are particularly effective in patients under 60 years with prodromal symptoms. 1
• Advise gradual positional changes: sit on the bedside for 2–3 minutes before standing, avoid prolonged standing. 1

Compression Garments:

• Use waist-high compression stockings (30–40 mmHg) and/or abdominal binders to reduce venous pooling. 1, 3

Postural Adjustments:

• Elevate the head of the bed by approximately 10 degrees during sleep to prevent nocturnal polyuria, maintain favorable fluid distribution, and ameliorate supine hypertension. 1, 3

Dietary Modifications:

• Eat smaller, more frequent meals to reduce postprandial hypotension. 1, 3
• Avoid alcohol, which causes both autonomic neuropathy and central volume depletion. 1

Exercise:

• Encourage regular physical activity to prevent deconditioning, which worsens orthostatic intolerance. 1, 3

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Pharmacologic Treatment (When Non-Pharmacologic Measures Fail)

The therapeutic goal is to minimize postural symptoms and improve functional capacity—not to restore normotension or achieve arbitrary blood pressure targets. 1, 3

First-Line Agent: Midodrine

Midodrine has the strongest evidence base among pressor agents, supported by three randomized placebo-controlled trials. 1

• Start at 2.5–5 mg three times daily (at roughly 4-hour intervals during waking hours), titrate up to 10 mg three times daily based on symptom response. 1, 3
• The last dose must be taken at least 3–4 hours before bedtime (not after 6 PM) to prevent supine hypertension during sleep. 1, 3
• Midodrine raises standing systolic BP by 15–30 mmHg for 2–3 hours via peripheral α₁-adrenergic vasoconstriction. 1
• Avoid concurrent use with other α-adrenergic agents (ephedrine, pseudoephedrine) due to additive supine hypertension risk. 1
• Use caution when combining with negative chronotropic drugs (beta-blockers, digoxin, non-dihydropyridine calcium channel blockers). 1

Second-Line or Combination Agent: Fludrocortisone

Fludrocortisone may be used as monotherapy or combined with midodrine when a single agent provides insufficient symptom control. 1, 3

• Start at 0.05–0.1 mg once daily, titrate to 0.1–0.3 mg daily (maximum 1.0 mg daily) based on clinical response. 1, 3
• Acts through sodium retention and vessel wall effects, expanding plasma volume via a complementary mechanism to midodrine's vasoconstriction. 1, 3
• Monitor for supine hypertension, hypokalemia, congestive heart failure, and peripheral edema. 1, 3
• Contraindicated in patients with active heart failure, severe renal disease, or pre-existing supine hypertension. 1
• Check electrolytes periodically due to mineralocorticoid-induced potassium wasting. 1

Combination Therapy for Refractory Cases:

When monotherapy fails, combine midodrine with fludrocortisone, as the agents act via complementary mechanisms (α₁-adrenergic vasoconstriction plus mineralocorticoid-mediated volume expansion). 1, 3

Alternative Agent: Droxidopa

Droxidopa is FDA-approved and particularly effective for neurogenic orthostatic hypotension in Parkinson's disease, pure autonomic failure, and multiple system atrophy. 1, 3

• May reduce falls in neurogenic orthostatic hypotension. 1
• Note: Concomitant carbidopa therapy can diminish droxidopa's efficacy by inhibiting peripheral conversion to norepinephrine. 1

Refractory Cases: Pyridostigmine

Pyridostigmine (60 mg three times daily) may be added for patients refractory to midodrine and fludrocortisone, particularly when supine hypertension limits further pressor use. 1, 3

• Enhances ganglionic sympathetic transmission by inhibiting acetylcholinesterase, raising BP preferentially in the upright position without worsening supine hypertension. 1
• Common side effects include nausea, vomiting, abdominal cramping, sweating, salivation, and urinary incontinence—generally manageable. 1
• Preferred agent when supine hypertension is a concern, as it does not worsen supine BP. 1

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Special Populations

Frail Elderly (≥85 years):

• Defer blood pressure-lowering treatment until office BP ≥140/90 mmHg in patients with pre-treatment symptomatic orthostatic hypotension, moderate-to-severe frailty, or limited life expectancy. 1, 3
• Use "as low as reasonably achievable" (ALARA) principle rather than strict 130/80 mmHg targets. 1
• Asymptomatic orthostatic hypotension during hypertension treatment should not trigger automatic down-titration of therapy, as intensive BP lowering may actually reduce orthostatic hypotension risk by improving baroreflex function. 4, 1

Diabetic Patients:

• Assess for cardiovascular autonomic neuropathy (CAN) in diabetic patients >50 years with orthostatic hypotension using cardiac autonomic reflex tests (CARTs). 1
• CAN is a Level A evidence risk marker for all-cause mortality and confers additional mortality risk beyond heart-rate variability abnormalities. 1
• Midodrine or droxidopa are preferred as "norepinephrine replacers" in neurogenic patterns. 3

Parkinson's Disease:

• Review antiparkinsonian medications as potential contributors. 3
• Droxidopa is particularly effective in this population. 1, 3

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Monitoring and Follow-Up

At each visit, measure both supine (or seated) and standing blood pressures after 5 minutes of rest, then at 1 and 3 minutes after standing. 1, 3

• Initial follow-up within 1–2 weeks after medication changes to assess symptom improvement, functional capacity, and development of supine hypertension. 1, 3
• Monitor for supine hypertension development, which can cause end-organ damage—this is the most important limiting factor for pressor therapy. 1
• If using fludrocortisone, check electrolytes, BUN, and creatinine periodically. 1
• Reassess orthostatic vital signs, symptom diary, falls assessment, and quality of life at ongoing visits. 3

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Common Pitfalls to Avoid

• Do not simply reduce the dose of offending medications—switch to alternative therapy. 1, 3
• Do not administer midodrine after 6 PM to prevent nocturnal supine hypertension. 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—assess hydration status, recent fluid intake, diuretic use, vomiting, diarrhea, or heat exposure. 1
• Do not measure only at 3 minutes—perform measurements at both 1 minute and 3 minutes after standing to detect early orthostatic hypotension. 2
• Do not use sit-to-stand testing (sensitivity only 15.5%)—adopt supine-to-stand as the preferred method. 2