What is the treatment for orthostatic hypotension?

Treatment of Orthostatic Hypotension

Begin with non-pharmacological interventions for all patients, and add pharmacological therapy with midodrine or fludrocortisone when symptoms persist despite conservative measures, with the goal of minimizing postural symptoms rather than normalizing blood pressure. 1

Initial Assessment and Reversible Causes

First, identify and eliminate reversible causes before initiating specific treatment:

• Discontinue or switch culprit medications that worsen orthostatic hypotension rather than simply reducing doses 1

  • Alpha-1 blockers (doxazosin, prazosin, terazosin) are the most problematic antihypertensives 2
  • Diuretics and vasodilators are the most frequent drug-induced causes 1
  • Centrally-acting agents (clonidine, methyldopa) commonly contribute 2
  • Avoid psychotropic drugs and α-adrenoreceptor antagonists when possible 1

• Evaluate for volume depletion, endocrine disorders, and neurogenic causes before assuming the diagnosis is idiopathic 1

• Measure blood pressure after 5 minutes lying/sitting, then at 1 and 3 minutes after standing to confirm the diagnosis (≥20 mmHg systolic or ≥10 mmHg diastolic drop) 1

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

These interventions should be implemented before or alongside pharmacological therapy:

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 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 to acutely raise blood pressure 1
• Use compression garments (thigh-high or waist-high stockings and abdominal binders) to reduce venous pooling 1
• Encourage physical activity and exercise to prevent deconditioning, which worsens orthostatic intolerance 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 reduce supine hypertension 1
• Eat smaller, more frequent meals to reduce post-prandial hypotension 1
• Implement gradual staged movements when changing positions 1

Pharmacological Management (When Non-Pharmacological Measures Fail)

The therapeutic goal is minimizing postural symptoms, not restoring normotension, to avoid excessive supine hypertension. 1

First-Line Medications

Midodrine (FDA-approved, preferred initial agent):

• Start with 2.5-5 mg three times daily, can increase standing systolic BP by 15-30 mmHg for 2-3 hours 1, 3
• Avoid the last dose after 6 PM to prevent supine hypertension during sleep 1
• Mechanism: Alpha-1 agonist causing arteriolar and venous constriction 3
• Peak effect: 1 hour after dosing, with some effect persisting 2-3 hours 3
• Critical warning: Can cause marked supine hypertension (BP >200 mmHg systolic); monitor carefully 3
• Use only in patients whose lives are considerably impaired despite standard care 3

Fludrocortisone (alternative first-line agent):

• Start with 0.05-0.1 mg once daily, titrate individually to 0.1-0.3 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, and pre-existing supine hypertension 1
• Evidence quality is limited to small, short-term trials with very low-certainty evidence 1

Second-Line Medications

Droxidopa (FDA-approved):

• Effective for neurogenic orthostatic hypotension due to Parkinson's disease, pure autonomic failure, and multiple system atrophy 1
• May reduce falls in these populations 1

Pyridostigmine (for refractory cases):

• Consider for elderly patients refractory to other treatments, with fewer side effects than fludrocortisone 1
• Does not cause fluid retention or supine hypertension, making it useful in diabetic patients 2
• Common side effects: Nausea, vomiting, abdominal cramping, sweating, salivation, urinary incontinence 1

Combination Therapy

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

Special Populations

Patients with Concurrent Hypertension

• Use long-acting dihydropyridine calcium channel blockers or RAS inhibitors as first-line antihypertensives, as these have minimal impact on orthostatic blood pressure 1, 2
• Test for orthostatic hypotension before starting or intensifying any blood pressure-lowering medication 2
• Avoid beta-blockers unless there are compelling indications 2

Diabetic Patients

• Assess for cardiovascular autonomic neuropathy in diabetic patients with orthostatic hypotension 1
• Consider pyridostigmine as it avoids fluid retention and supine hypertension 2

Patients on Hemodialysis

• Midodrine is removed by dialysis; timing of doses relative to dialysis sessions requires consideration 3

Monitoring and Safety

Critical monitoring parameters:

• Measure supine and sitting blood pressure regularly to detect supine hypertension (rises of 16/8 mmHg supine and 20/10 mmHg sitting are common with fludrocortisone) 1
• Check electrolytes periodically when using fludrocortisone due to potassium wasting 1
• Monitor for bradycardia when using midodrine with cardiac glycosides, beta blockers, or other rate-lowering agents 3
• Reassess within 1-2 weeks after medication changes 1

Important caveats:

• Balance the risk of falls and injury from orthostatic hypotension against cardiovascular protection from blood pressure control 1
• Avoid supine/nocturnal hypertension, as this can cause end-organ damage 1
• Continue midodrine only in patients who report significant symptomatic improvement, as clinical benefits beyond standing BP improvement have not been fully established 3

Treatment Algorithm

1. Identify and eliminate reversible causes (medications, volume depletion) 1
2. Implement all appropriate non-pharmacological measures (fluid/salt, compression, physical countermeasures, positional changes) 1
3. If symptoms persist, add midodrine 2.5-5 mg three times daily (last dose before 6 PM) 1, 3
4. If midodrine insufficient or contraindicated, use fludrocortisone 0.05-0.1 mg daily 1
5. For inadequate response to monotherapy, combine midodrine and fludrocortisone 1
6. For refractory cases, consider pyridostigmine or droxidopa 1
7. Monitor closely for supine hypertension and adjust therapy accordingly 1