What are the treatment options for orthostatic hypotension?

Treatment of Orthostatic Hypotension

Begin with non-pharmacological interventions for all patients, and add pharmacological therapy only when symptoms persist despite these measures, with midodrine as the first-line medication and fludrocortisone as second-line or combination therapy. 1

Initial Evaluation and Reversible Causes

Before initiating treatment, identify and eliminate reversible causes:

• Discontinue or switch culprit medications as the first-line approach, particularly diuretics, vasodilators, alpha-1 blockers (doxazosin, prazosin, terazosin, tamsulosin), centrally-acting agents (clonidine, methyldopa), and psychotropic drugs 1, 2
• Switch rather than reduce doses of blood pressure medications that worsen orthostatic hypotension—for patients requiring continued antihypertensive therapy, use long-acting dihydropyridine calcium channel blockers or RAS inhibitors as preferred agents 1, 2
• Evaluate for volume depletion, neurogenic causes, and endocrine disorders 1
• Measure blood pressure after 5 minutes of sitting/lying, then at 1 and 3 minutes after standing to confirm diagnosis 1

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

Fluid and Salt Management

• 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 therapy: Drink ≥480 mL of water for temporary relief, with peak effect at 30 minutes—notably, plain water is more effective than salt water for acute pressor response 1, 3

Physical Countermeasures

• Teach leg crossing, squatting, stooping, and muscle tensing during symptomatic episodes—particularly effective in patients under 60 years with prodromal symptoms 1
• Use waist-high compression stockings (30-40 mmHg) and abdominal binders to reduce venous pooling 1

Postural and Lifestyle Modifications

• Elevate head of bed by 10 degrees during sleep to prevent nocturnal polyuria, maintain favorable fluid distribution, and ameliorate supine hypertension 1
• Implement gradual staged movements with postural changes 1
• Eat smaller, more frequent meals to reduce post-prandial hypotension 1
• Encourage physical activity and exercise to avoid deconditioning 1
• Avoid taking last medication dose after 6 PM to prevent supine hypertension during sleep 1

Pharmacological Management

First-Line: Midodrine

Midodrine is the first-line pharmacological therapy with the strongest evidence base among pressor agents, supported by three randomized placebo-controlled trials and FDA approval. 1, 4

• Starting dose: 2.5-5 mg three times daily 1, 4
• Timing: Last dose at least 3-4 hours before bedtime to prevent supine hypertension 1, 4
• Mechanism: Alpha-1 agonist causing arteriolar and venous constriction 4
• Effect: Increases standing systolic BP by 15-30 mmHg for 2-3 hours 1, 4
• Peak effect: 1 hour after dosing 4
• Monitoring: Watch for supine hypertension (BP >200 mmHg systolic), bradycardia, and urinary retention 4
• Contraindications: Use cautiously with cardiac glycosides, beta blockers, and other vasoconstrictors 4

Second-Line: Fludrocortisone

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

• Starting dose: 0.05-0.1 mg once daily 1
• Titration: Increase to 0.1-0.3 mg daily based on response (maximum 1.0 mg daily) 1
• Mechanism: Mineralocorticoid causing sodium retention and vessel wall effects 1
• Monitoring: Check for supine hypertension (most important limiting factor), hypokalemia, peripheral edema, and congestive heart failure 1
• Contraindications: Avoid in active heart failure, significant cardiac dysfunction, severe renal disease, and pre-existing supine hypertension 1
• Evidence quality: Limited, with only very low-certainty evidence from small, short-term trials 1

Combination Therapy

• For non-responders to monotherapy, combine midodrine and fludrocortisone 1

Alternative Agents

Droxidopa (FDA-approved):

• Particularly effective for neurogenic orthostatic hypotension in Parkinson's disease, pure autonomic failure, and multiple system atrophy 1
• May reduce falls 1

Pyridostigmine:

• Beneficial for refractory orthostatic hypotension in elderly patients 1
• Favorable side effect profile compared to fludrocortisone—does not cause fluid retention or supine hypertension 1, 2
• Common side effects: nausea, vomiting, abdominal cramping, sweating, salivation, urinary incontinence 1
• Supported by 2017 ACC/AHA/HRS guidelines for neurogenic orthostatic hypotension refractory to other treatments 1

Treatment Goals and Monitoring

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

• Continue midodrine only for patients who report significant symptomatic improvement 4
• Balance increasing standing BP against the risk of worsening supine hypertension 1
• Monitor for supine hypertension development, which can cause end-organ damage 1
• Reassess within 1-2 weeks after medication changes 1
• Measure BP after 5 minutes lying/sitting, then at 1 and 3 minutes after standing to document orthostatic changes 1

Special Populations

Patients with Concurrent Hypertension

• Use long-acting dihydropyridine calcium channel blockers or RAS inhibitors as first-line antihypertensive agents 1, 2
• Test for orthostatic hypotension before starting or intensifying any blood pressure-lowering medication 1, 2

Patients with Heart Failure and Low Blood Pressure

• Prioritize SGLT2 inhibitors and mineralocorticoid receptor antagonists, which have the least impact on blood pressure 2

Diabetic Patients

• Assess for cardiovascular autonomic neuropathy 1
• Consider pyridostigmine, which does not cause fluid retention or supine hypertension 2

Elderly/Frail Patients (≥85 years)

• If antihypertensive therapy needed, use long-acting dihydropyridine calcium channel blockers or RAS inhibitors first, followed by low-dose diuretics if tolerated 2
• Start midodrine at lower dose (2.5 mg) in patients with renal impairment 4

Common Pitfalls to Avoid

• Do not simply reduce doses of offending antihypertensives—switch to alternative agents instead 1, 2
• Do not allow patients to take midodrine if they will be supine for any length of time—avoid late evening doses 1, 4
• Do not add salt to water for acute pressor response—plain water is paradoxically more effective than salt water 3
• Do not use alpha-1 blockers, which antagonize midodrine's effects 4
• Do not confuse orthostatic tremor with orthostatic hypotension, which require different management approaches 5