What are the treatment options for a patient with orthostatic hypotension?

Treatment of Orthostatic Hypotension

Begin by discontinuing medications that cause orthostatic hypotension—particularly alpha-blockers, diuretics, and vasodilators—as drug-induced autonomic failure is the most frequent cause, and switching to alternative agents rather than dose reduction is the primary treatment strategy. 1

Step 1: Identify and Eliminate Reversible Causes

Medication Review (Most Critical First Step)

• Immediately discontinue alpha-1 blockers (doxazosin, prazosin, terazosin, tamsulosin) as these are the most problematic agents, especially in older adults 1, 2
• Stop or switch diuretics if causing volume depletion, as these are among the most frequent culprits of drug-induced orthostatic hypotension 1, 2
• Discontinue vasodilators (hydralazine, minoxidil) and centrally-acting agents (clonidine, methyldopa) 1, 2
• Avoid beta-blockers unless compelling indications exist (e.g., heart failure, post-MI), as they can exacerbate orthostatic hypotension 1
• Switch, don't reduce doses: For patients requiring continued antihypertensive therapy, replace offending medications with long-acting dihydropyridine calcium channel blockers or RAS inhibitors rather than simply lowering doses 1, 2

Other Reversible Causes to Address

• Correct volume depletion from dehydration or blood loss 1
• Eliminate alcohol consumption, as it causes both direct autonomic dysfunction and central volume depletion 1
• Evaluate for endocrine disorders (adrenal insufficiency, hypothyroidism) 1

Step 2: Implement Non-Pharmacological Measures (For All Patients)

Volume Expansion Strategies

• Increase fluid intake to 2-3 liters daily unless contraindicated by heart failure 1
• Increase salt intake to 6-9 grams daily if not contraindicated 1
• Acute water bolus: Drink ≥480 mL of water for temporary relief, with peak effect at 30 minutes 1

Positional and Physical Maneuvers

• Elevate head of bed by 10 degrees during sleep to prevent nocturnal polyuria, maintain fluid distribution, and reduce supine hypertension 1
• Teach physical counter-maneuvers: leg crossing, squatting, stooping, and muscle tensing during symptomatic episodes—particularly effective in patients under 60 years with prodromal symptoms 1
• Gradual staged movements with postural changes to allow cardiovascular compensation 1

Compression Garments

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

Dietary Modifications

• Eat smaller, more frequent meals to reduce post-prandial hypotension 1
• Encourage physical activity and exercise to avoid deconditioning, which worsens orthostatic intolerance 1

Step 3: Pharmacological Treatment (When Non-Pharmacological Measures Fail)

Treatment Goal

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

First-Line Pharmacological Agents

Midodrine (Strongest Evidence Base)

• Midodrine has the strongest evidence among pressor agents, with three randomized placebo-controlled trials demonstrating efficacy 1
• Initial dose: 2.5-5 mg three times daily, titrate up to 10 mg three times daily based on response 1
• Increases standing systolic BP by 15-30 mmHg for 2-3 hours 1
• Critical timing: Last dose must be taken at least 3-4 hours before bedtime (not after 6 PM) to prevent supine hypertension during sleep 1
• Mechanism: Alpha-1 adrenergic agonist causing arteriolar and venous constriction 1

Fludrocortisone

• Initial dose: 0.05-0.1 mg once daily, titrate individually to 0.1-0.3 mg daily (maximum 1.0 mg daily) 1
• Mechanism: Mineralocorticoid that increases plasma volume through sodium retention and vessel wall effects 1
• Monitor for: supine hypertension (most important limiting factor), hypokalemia, congestive heart failure, and peripheral edema 1
• Contraindications: Active heart failure, significant cardiac dysfunction, severe renal disease, or pre-existing supine hypertension 1
• Evidence quality is limited: Only very low-certainty evidence from small, short-term trials 1

Droxidopa

• FDA-approved for neurogenic orthostatic hypotension due to Parkinson's disease, pure autonomic failure, and multiple system atrophy 1, 3
• May reduce falls in these populations 1
• Important limitation: Effectiveness beyond 2 weeks is uncertain; patients should be evaluated periodically to determine if droxidopa continues to provide benefit 3
• Evidence: Showed statistically significant 0.9 unit decrease in dizziness at Week 1 versus placebo (P=0.028), but effect did not persist beyond Week 1 3

Second-Line and Combination Therapy

Combination Therapy

• For non-responders to monotherapy: Consider combining midodrine and fludrocortisone, as they work through different mechanisms (alpha-1 adrenergic stimulation vs. sodium retention) 1
• Add fludrocortisone 0.1-0.3 mg once daily if midodrine alone provides insufficient symptom control 1

Pyridostigmine (For Refractory Cases)

• Recommended for refractory orthostatic hypotension in elderly patients who have not responded to first-line treatments 1
• Starting dose: 60 mg orally three times daily (maximum 600 mg daily) 1
• Mechanism: Acetylcholinesterase inhibitor that enhances ganglionic sympathetic transmission 1
• Key advantage: Does NOT worsen supine hypertension or cause fluid retention, making it preferred when supine hypertension is a concern 1
• Favorable side effect profile compared to alternatives like fludrocortisone 1
• Common side effects: Nausea, vomiting, abdominal cramping, sweating, salivation, urinary incontinence (generally manageable) 1

Other Agents for Specific Situations

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

Step 4: Monitoring and Safety

Blood Pressure Measurement Protocol

• Measure BP after 5 minutes of sitting/lying, then at 1 and 3 minutes after standing to document orthostatic changes 1
• Monitor both supine and standing BP at each visit to detect treatment-induced supine hypertension 1

Follow-Up Schedule

• Reassess within 1-2 weeks after medication changes 1
• Monitor orthostatic vital signs at each follow-up visit 1
• For droxidopa specifically: Evaluate periodically to determine if continuing benefit exists beyond 2 weeks 3

Critical Monitoring Parameters

• Supine hypertension: Most important limiting factor with pressor agents 1
• Electrolytes: Check periodically if using fludrocortisone due to potassium wasting 1
• BUN and creatinine: Monitor if using fludrocortisone 1

Special Considerations

Patients with Concurrent Hypertension and Orthostatic Hypotension

• Preferred antihypertensives: Long-acting dihydropyridine calcium channel blockers or RAS inhibitors as first-line therapy 1, 2
• Avoid: Alpha-blockers, beta-blockers (unless compelling indication), and excessive diuretic use 1, 2
• Consider shorter-acting antihypertensives at bedtime to manage supine hypertension 1

Elderly and Frail Patients (≥85 Years)

• Defer BP-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
• Target "as low as reasonably achievable" (ALARA principle) rather than strict 130/80 mmHg 1
• Asymptomatic orthostatic hypotension during treatment should NOT trigger automatic down-titration, as intensive BP lowering may actually reduce OH risk by improving baroreflex function 1

Diabetic Patients

• Assess for cardiovascular autonomic neuropathy in diabetic patients with orthostatic hypotension 1
• Consider α-lipoic acid for painful diabetic neuropathy, potentially beneficial for autonomic function 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 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
• Do NOT withhold treatment based on age alone unless diastolic BP is lowered to 55-60 mmHg 1