What are the best treatment options for an older adult patient with orthostatic hypotension?

Treatment of Orthostatic Hypotension in Older Adults

Non-pharmacological interventions should be implemented first-line for all patients with orthostatic hypotension, and if symptoms persist despite these measures, midodrine is the first-choice pharmacological agent with the strongest evidence base, followed by fludrocortisone or droxidopa as alternatives. 1, 2

Initial Assessment and Reversible Causes

Before initiating any treatment, confirm the diagnosis by measuring blood pressure after 5 minutes of sitting or lying, then at 1 and/or 3 minutes after standing—a drop of ≥20 mmHg systolic or ≥10 mmHg diastolic confirms orthostatic hypotension. 3, 1

The single most important first step is identifying and discontinuing medications that cause or worsen orthostatic hypotension, as drug-induced autonomic failure is the most frequent cause of this condition. 1 The primary culprits include:

• Diuretics and vasodilators (the most important offending agents) 1
• Alpha-1 blockers (doxazosin, prazosin, terazosin, tamsulosin) 1, 4
• Centrally-acting antihypertensives (clonidine, methyldopa) 4
• Psychotropic medications 1

Critical principle: Switch offending medications to alternatives rather than simply reducing doses, as dose reduction alone is inadequate. 3, 1

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

These interventions form the foundation of treatment and should be implemented before or alongside pharmacotherapy:

Volume Expansion Strategies

• Increase fluid intake to 2-3 liters daily (unless contraindicated by heart failure) 1
• Increase salt consumption to 6-9 grams daily (unless contraindicated) 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—these are particularly effective in patients under 60 years with prodromal symptoms 1
• Implement gradual staged movements when changing positions 1

Compression Therapy

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

Positional and Dietary 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
• 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 Management (When Non-Pharmacological Measures Fail)

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

First-Line Pharmacological Agent: Midodrine

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

Dosing:

• Start at 2.5-5 mg three times daily 1, 2
• The last dose must be taken at least 3-4 hours before bedtime (not after 6 PM) to prevent supine hypertension during sleep 1, 2
• Can increase standing systolic BP by 15-30 mmHg for 2-3 hours 1, 2

Mechanism: Alpha-1 adrenergic agonist that causes arteriolar and venous constriction, increasing vascular tone and blood pressure without stimulating cardiac beta-receptors. 2

Critical monitoring: Measure supine blood pressure regularly to detect treatment-induced supine hypertension, which is the most important limiting factor. 1, 2

Second-Line Agents

Fludrocortisone

Use when midodrine alone provides insufficient symptom control or as an alternative first-line agent. 1

Dosing:

• Start at 0.05-0.1 mg once daily 1
• Titrate to 0.1-0.3 mg daily based on response 1
• Maximum dose: 1.0 mg daily 1

Mechanism: Mineralocorticoid that acts through sodium retention and vessel wall effects, increasing plasma volume. 1

Contraindications:

• Active heart failure or significant cardiac dysfunction 1
• Pre-existing supine hypertension 1
• Severe renal disease where sodium retention would be harmful 1

Monitoring requirements:

• Check for supine hypertension (most important limiting factor) 1
• Monitor electrolytes periodically for hypokalemia 1
• Watch for peripheral edema and congestive heart failure 1

Droxidopa

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

Combination Therapy

For non-responders to monotherapy, consider combining midodrine with fludrocortisone, as they work through complementary mechanisms (alpha-1 adrenergic stimulation vs. sodium retention). 1

Refractory Cases

Pyridostigmine may be beneficial in patients with syncope due to neurogenic orthostatic hypotension who are refractory to other treatments, with a favorable side effect profile compared to alternatives. 1 Common side effects include nausea, vomiting, abdominal cramping, sweating, and salivation, which are generally manageable. 1

Special Considerations for Patients with Concurrent Hypertension

For patients with both hypertension and orthostatic hypotension:

• Pursue non-pharmacological approaches as first-line treatment 3
• When antihypertensive therapy is necessary, use long-acting dihydropyridine calcium channel blockers or RAS inhibitors as first-line agents 3, 4
• Avoid beta-blockers unless compelling indications exist 3
• Avoid alpha-blockers 3
• Switch medications that worsen orthostatic hypotension to alternatives rather than de-intensifying therapy 3, 1

Common Pitfalls to Avoid

• Do NOT simply reduce the dose of offending medications—switch to alternatives instead 1
• Do NOT administer midodrine after 6 PM due to risk of 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
• Do NOT use beta-blockers for orthostatic hypotension—they are not effective and may aggravate bradycardia 1

Monitoring and Follow-Up

• Reassess within 1-2 weeks after medication changes 1
• Monitor orthostatic vital signs at each follow-up visit 1
• Measure blood pressure in both supine/sitting and standing positions to balance symptom improvement against supine hypertension risk 1
• Continue midodrine only for patients who report significant symptomatic improvement 2