What is the treatment for orthostatic hypotension?

Treatment of Orthostatic Hypotension

Begin with non-pharmacological measures and medication review; if symptoms persist, initiate midodrine as first-line pharmacological therapy, with fludrocortisone as an alternative or add-on agent.

Immediate Assessment and Reversible Causes

• Confirm the diagnosis by measuring blood pressure after 5 minutes supine or seated, then at 1 and 3 minutes after standing; a drop ≥20 mmHg systolic or ≥10 mmHg diastolic defines orthostatic hypotension 1.

• Identify and discontinue culprit medications as the primary treatment strategy, since drug-induced autonomic failure is the most frequent cause of orthostatic hypotension 1. The most problematic agents include:

  • Alpha-1 blockers (doxazosin, prazosin, terazosin, tamsulosin) 1, 2
  • Diuretics, especially when causing volume depletion 1, 2
  • Centrally-acting antihypertensives (clonidine, methyldopa) 1, 2
  • Vasodilators (hydralazine, minoxidil) 2
  • Beta-blockers (unless compelling indication exists, such as heart failure or recent MI) 2

• Switch offending medications to alternatives rather than simply reducing the dose—for example, replace problematic agents with long-acting dihydropyridine calcium channel blockers or RAS inhibitors, which have minimal impact on orthostatic blood pressure 1, 2.

• Assess for volume depletion from dehydration, blood loss, or excessive diuresis, and correct the deficit 1.

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

Fluid and Salt Expansion

• Increase fluid intake to 2–3 liters daily unless contraindicated by heart failure 1, 3.
• Increase dietary sodium to 6–9 grams daily if not contraindicated by hypertension or heart failure 1, 3.
• Acute water ingestion of ≥480 mL provides temporary relief with peak effect at 30 minutes 1.

Physical Countermaneuvers

• 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, 3.
• Advise gradual staged movements with postural changes—sit on the bedside for 2–3 minutes before standing 1.

Compression Garments

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

Positional and Dietary Strategies

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

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Pharmacological Management (When Non-Pharmacological Measures Fail)

First-Line Agent: Midodrine

Midodrine has the strongest evidence base among pressor agents, supported by three randomized placebo-controlled trials and FDA approval 1, 4, 5.

• Dosing: Start at 2.5–5 mg three times daily (roughly every 4 hours during waking hours), titrating up to 10 mg three times daily based on response 1, 5.
• Timing: 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.
• Mechanism: Alpha-1 adrenergic agonist that increases standing systolic blood pressure by 15–30 mmHg for 2–3 hours through peripheral vasoconstriction 1.
• FDA indication: Approved for symptomatic orthostatic hypotension in patients whose lives are considerably impaired despite standard care 4.

Alternative or Add-On Agent: Fludrocortisone

• Dosing: Start at 0.05–0.1 mg once daily, titrate to 0.1–0.3 mg daily based on response 1, 3, 6.
• Mechanism: Mineralocorticoid that expands plasma volume through sodium retention and vessel wall effects 1.
• Monitoring: Check for supine hypertension, hypokalemia, congestive heart failure, and peripheral edema 1.
• Contraindications: Avoid in patients with active heart failure, severe renal disease, or pre-existing supine hypertension 1.

Combination Therapy for Inadequate Response

When monotherapy fails, combine midodrine with fludrocortisone because they act via complementary mechanisms (vasoconstriction plus volume expansion) 1, 6.

Second-Line Agent: Droxidopa

• FDA-approved for neurogenic orthostatic hypotension caused by Parkinson's disease, multiple system atrophy, pure autonomic failure, dopamine beta-hydroxylase deficiency, and non-diabetic autonomic neuropathy 1, 7.
• Particularly effective in neurogenic orthostatic hypotension and may reduce falls 1.
• Note: Effectiveness beyond 2 weeks has not been established; continued effectiveness should be assessed periodically 7.

Refractory Cases: Pyridostigmine

• Dosing: 60 mg three times daily 1.
• Indication: For elderly patients or those with neurogenic orthostatic hypotension refractory to first-line agents, especially when supine hypertension is a concern because pyridostigmine does not worsen supine blood pressure 1.
• Mechanism: Acetylcholinesterase inhibitor that enhances ganglionic sympathetic transmission 1.
• Side effects: Nausea, vomiting, abdominal cramping, sweating, salivation, urinary incontinence (generally manageable) 1.

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Treatment Goals and Monitoring

• The therapeutic objective is minimizing postural symptoms and improving functional capacity, NOT restoring normotension 1, 3, 6, 8.

• At each follow-up visit, measure blood pressure after 5 minutes supine/seated, then at 1 and 3 minutes after standing to document both orthostatic changes and supine hypertension 1.

• Monitor for supine hypertension, which is the most important limiting factor and can cause end-organ damage 1, 3.

• Reassess within 1–2 weeks after medication changes 1.

• If fludrocortisone is used, check electrolytes periodically due to mineralocorticoid effects that can cause potassium wasting 1.

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Common Pitfalls to Avoid

• Do not simply reduce the dose of offending medications—switch to alternative agents with minimal orthostatic impact 1, 2.

• Do not administer midodrine after 6 PM to avoid 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 1.

• Avoid beta-blockers unless compelling indications exist (e.g., heart failure, recent MI) 2.

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Special Populations

Diabetic Patients

• Assess for cardiovascular autonomic neuropathy in diabetic patients with orthostatic hypotension 1.
• Consider alpha-lipoic acid for painful diabetic neuropathy and potential autonomic function benefits 1, 3.

Elderly or Frail Patients

• Defer blood pressure-lowering treatment in patients ≥85 years with pre-treatment symptomatic orthostatic hypotension, moderate-to-severe frailty, or limited life expectancy until office blood pressure is ≥140/90 mmHg 1.
• When antihypertensive therapy is needed, prefer long-acting dihydropyridine calcium channel blockers or RAS inhibitors as first-line agents 1, 2.

Patients with Concurrent Hypertension and Orthostatic Hypotension

• Use long-acting dihydropyridine calcium channel blockers or RAS inhibitors as first-line therapy 1, 2.
• Asymptomatic orthostatic hypotension during treatment should not trigger automatic down-titration, as intensive blood pressure lowering may actually reduce orthostatic hypotension risk by improving baroreflex function 1.