What is the treatment for orthostatic hypotension?

Treatment of Orthostatic Hypotension

Begin with non-pharmacological interventions and medication review, then add midodrine as first-line pharmacological therapy if symptoms persist, reserving fludrocortisone for combination therapy or when midodrine is insufficient. 1

Initial Management: Identify and Eliminate Reversible Causes

• Discontinue or switch medications that worsen orthostatic hypotension rather than simply reducing doses—this is the principal treatment strategy since drug-induced autonomic failure is the most frequent cause. 1
• The most important culprits are diuretics, vasodilators, alpha-1 blockers (doxazosin, prazosin, terazosin), and centrally-acting agents (clonidine, methyldopa). 1, 2
• For patients requiring continued antihypertensive therapy, switch to long-acting dihydropyridine calcium channel blockers or RAS inhibitors (ACE inhibitors/ARBs), which have minimal impact on orthostatic blood pressure. 2
• Avoid alcohol, as it induces both autonomic neuropathy and central volume depletion. 1

Non-Pharmacological Interventions (Implement for ALL Patients)

Fluid and Salt Management:

• Increase fluid intake to 2-3 liters daily and salt consumption to 6-9 grams daily, unless contraindicated by heart failure. 1
• Acute water ingestion of ≥480 mL provides temporary relief with peak effect at 30 minutes. 1

Physical Counter-Maneuvers:

• Teach leg crossing, squatting, stooping, and muscle tensing during symptomatic episodes—particularly effective in patients under 60 years with prodromal symptoms. 1

Compression Garments:

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

Positional Strategies:

• Elevate the head of bed by 10 degrees during sleep to prevent nocturnal polyuria, maintain favorable fluid distribution, and ameliorate nocturnal hypertension. 1
• Teach gradual staged movements with postural changes. 1

Dietary Modifications:

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

First-Line Pharmacological Treatment: Midodrine

When non-pharmacological measures fail to adequately control symptoms, midodrine is the first-line medication with the strongest evidence base—three randomized placebo-controlled trials demonstrate efficacy. 1, 3

Dosing:

• Start at 2.5-5 mg three times daily. 1, 3
• Titrate individually up to 10 mg three times daily based on response. 1
• Critical timing: Take the last dose at least 3-4 hours before bedtime (not after 6 PM) to prevent supine hypertension during sleep. 1, 3

Mechanism and Effects:

• Midodrine is an alpha-1 adrenergic agonist causing arteriolar and venous constriction. 1
• Increases standing systolic BP by 15-30 mmHg for 2-3 hours. 1

Monitoring:

• Measure blood pressure after 5 minutes lying/sitting, then at 1 and 3 minutes after standing to document orthostatic changes. 1
• Monitor for supine hypertension development, which can cause end-organ damage. 1
• Watch for bradycardia (pulse slowing, increased dizziness, syncope)—discontinue if this occurs. 3

Precautions:

• Use cautiously with cardiac glycosides, beta blockers, or other agents that reduce heart rate. 3
• Avoid concomitant use with other vasoconstrictors (phenylephrine, pseudoephedrine, ephedrine). 3
• Use with caution in urinary retention, diabetes, and renal/hepatic impairment (start at 2.5 mg in renal impairment). 3

Second-Line or Combination Therapy: Fludrocortisone

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

Dosing:

• Start at 0.05-0.1 mg once daily. 1
• Titrate individually to 0.1-0.3 mg daily (maximum 1.0 mg daily). 1

Mechanism:

• Acts through sodium retention and vessel wall effects to increase plasma volume. 1

Combination Therapy:

• For non-responders to monotherapy, combine midodrine and fludrocortisone—they work through complementary mechanisms (alpha-1 adrenergic stimulation versus sodium retention). 1

Monitoring:

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

Contraindications:

• Avoid in active heart failure, significant cardiac dysfunction, severe renal disease, or pre-existing supine hypertension. 1

Alternative Pharmacological Options

Droxidopa:

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

Pyridostigmine:

• Consider for refractory orthostatic hypotension in elderly patients who have not responded to other treatments. 1
• Favorable side effect profile compared to fludrocortisone (fewer cardiovascular risks). 1
• Does not cause fluid retention or supine hypertension. 2
• Common side effects: nausea, vomiting, abdominal cramping, sweating, salivation, urinary incontinence. 1

Treatment Goals and Monitoring

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

• Balance the benefits of increasing standing blood pressure against the risk of worsening supine hypertension. 1
• Reassess patients within 1-2 weeks after medication changes. 1
• Monitor orthostatic vital signs at each follow-up visit. 1
• Continue treatment only for patients who report significant symptomatic improvement. 3

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. 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
• Beta-blockers are not effective and may aggravate bradycardia—avoid unless there are compelling indications. 1, 2