What are the treatment options for orthostatic hypotension, especially in older adults?

Treatment of Orthostatic Hypotension

Start with non-pharmacological interventions as first-line therapy, and if symptoms persist despite these measures, initiate midodrine 2.5-5 mg three times daily (last dose before 6 PM), adding fludrocortisone 0.05-0.1 mg daily only if midodrine alone provides insufficient symptom control. 1, 2

Initial Assessment and Reversible Causes

• Confirm orthostatic hypotension by measuring blood pressure after 5 minutes of sitting or lying, then at 1 and 3 minutes after standing—a drop of ≥20 mmHg systolic or ≥10 mmHg diastolic confirms the diagnosis 1, 2
• Identify and discontinue medications that worsen orthostatic hypotension: alpha-1 blockers (doxazosin, prazosin, terazosin, tamsulosin), diuretics, vasodilators, and centrally acting agents 2, 3
• Switch offending medications to alternative therapy rather than simply reducing doses—for example, replace alpha-blockers with long-acting dihydropyridine calcium channel blockers or RAS inhibitors if blood pressure control is needed 2, 3
• Evaluate for volume depletion, endocrine disorders, and alcohol use as reversible contributors 2

Non-Pharmacological Interventions (First-Line)

These measures should be implemented in all patients before or alongside pharmacological treatment: 1, 2

Volume Expansion

• Increase fluid intake to 2-3 liters daily unless contraindicated by heart failure 1, 2
• Increase salt intake to 6-9 grams daily if not contraindicated 1, 2
• Acute water ingestion of ≥480 mL provides temporary relief with peak effect at 30 minutes—useful for planned activities requiring standing 1, 2

Postural Modifications

• Elevate the head of the bed by 10 degrees during sleep to prevent nocturnal polyuria, maintain favorable fluid distribution, and ameliorate nocturnal hypertension 1, 2
• Teach gradual staged movements with postural changes—avoid rapid standing 1, 2
• Instruct patients in physical counter-maneuvers: leg crossing, squatting, stooping, and muscle tensing during symptomatic episodes (particularly effective in patients under 60 years with prodromal symptoms) 1, 2

Mechanical Compression

• Use waist-high compression stockings (30-40 mmHg) and abdominal binders to reduce venous pooling 1, 2
• Note: Compression stockings are often poorly tolerated by elderly patients due to difficulty with application/removal and stigma concerns, making them less practical despite guideline recommendations 4

Dietary Modifications

• Eat smaller, more frequent meals to reduce postprandial hypotension 1, 2

Pharmacological Treatment (When Non-Pharmacological Measures Insufficient)

The therapeutic goal is minimizing postural symptoms and improving functional capacity, NOT restoring normotension. 1, 2

First-Line: Midodrine

Midodrine has the strongest evidence base among pressor agents, with three randomized placebo-controlled trials demonstrating efficacy. 1, 2

• Starting dose: 2.5-5 mg three times daily 1, 2, 5
• Titration: Increase up to 10 mg three times daily based on response 1, 2
• Critical timing: Last dose must be taken at least 3-4 hours before bedtime (not later than 6 PM) to prevent supine hypertension during sleep 1, 2, 5
• Mechanism: Alpha-1 agonist that increases vascular tone through arteriolar and venous constriction 1
• Expected effect: Increases standing systolic BP by 15-30 mmHg for 2-3 hours 1
• Monitoring: Check supine blood pressure regularly to detect treatment-induced supine hypertension 1, 5
• Contraindications/Cautions: Use cautiously with cardiac glycosides, beta-blockers, urinary retention, and in patients with renal or hepatic impairment (start at 2.5 mg) 5

Second-Line or Adjunctive: Fludrocortisone

Add fludrocortisone only if midodrine alone provides insufficient symptom control, or use as monotherapy if midodrine is contraindicated. 1, 2

• Starting dose: 0.05-0.1 mg once daily 1, 2
• Titration: Increase to 0.1-0.3 mg daily based on response (maximum 1.0 mg daily) 1, 2
• Mechanism: Mineralocorticoid that acts through sodium retention and vessel wall effects 1, 2
• Monitoring requirements: Check for supine hypertension, hypokalemia, congestive heart failure, and peripheral edema 1, 2
• Absolute contraindications: Active heart failure, significant cardiac dysfunction, or pre-existing supine hypertension 1, 2

Alternative Agents for Refractory Cases

Droxidopa:

• FDA-approved for neurogenic orthostatic hypotension, particularly effective in Parkinson's disease, pure autonomic failure, and multiple system atrophy 2
• May reduce falls in these populations 2

Pyridostigmine:

• Preferred agent when supine hypertension is a major concern, as it does not worsen supine blood pressure 2, 3
• Starting dose: 60 mg orally three times daily 2
• Mechanism: Acetylcholinesterase inhibitor that enhances ganglionic sympathetic transmission 2
• Common side effects: Nausea, vomiting, abdominal cramping, sweating, salivation, urinary incontinence (generally manageable) 2
• Consider for elderly patients refractory to first-line treatments, especially those with concurrent supine hypertension or cardiac dysfunction 2, 3

Special Considerations in Older Adults

Intensive blood pressure lowering does not increase the risk of orthostatic hypotension or falls in elderly patients—in fact, it may reduce orthostatic hypotension by improving baroreflex function and reducing left ventricular hypertrophy. 6, 1

• Asymptomatic orthostatic hypotension during hypertension treatment should NOT trigger automatic down-titration of therapy 6, 1
• For patients aged ≥85 years or those with moderate-to-severe frailty requiring both hypertension treatment and orthostatic hypotension management, long-acting dihydropyridine calcium channel blockers or RAS inhibitors are preferred first-line antihypertensive agents 1, 3
• Defer blood pressure-lowering treatment in patients ≥85 years with orthostatic hypotension until blood pressure is >140/90 mmHg 2

Combination Therapy for Refractory Symptoms

• Midodrine plus fludrocortisone: These agents work through complementary mechanisms (alpha-1 adrenergic stimulation vs. sodium retention) and can be combined for refractory cases 2
• Ensure adequate salt (6-10 g daily) and fluid (2-3 L daily) intake as adjunctive measures when using pharmacological therapy 2

Critical Monitoring Parameters

• Measure blood pressure in both supine/sitting and standing positions at each visit 2, 3
• Reassess patients within 1-2 weeks after medication initiation or dose changes 2
• Monitor for symptoms: dizziness, lightheadedness, falls, syncope 3
• Check electrolytes periodically if using fludrocortisone due to potassium-wasting effects 2
• Balance the benefits of increasing standing blood pressure against the risk of worsening supine hypertension 2

Common Pitfalls to Avoid

• Do not simply reduce the dose of offending medications—switch to alternative therapy 2, 3
• Do not administer midodrine after 6 PM 2
• Do not use fludrocortisone in patients with heart failure or supine hypertension 2
• Do not combine multiple vasodilating agents (ACE inhibitors + calcium channel blockers + diuretics) without careful monitoring 2
• Do not overlook volume depletion as a contributing factor 2
• Do not withhold treatment based on age alone 2