What medication is used to treat orthostatic (postural) hypotension?

Treatment of Orthostatic Hypotension

For symptomatic orthostatic hypotension, start with midodrine 2.5-5 mg three times daily (last dose before 6 PM) or fludrocortisone 0.05-0.1 mg once daily as first-line pharmacological therapy, after implementing non-pharmacological measures including increased fluid (2-3 liters daily) and salt intake (6-9g daily). 1, 2, 3

Non-Pharmacological Management (Always Implement First)

Before initiating medications, implement these evidence-based interventions:

• Increase fluid intake to 2-3 liters daily and salt consumption to 6-9g daily, unless contraindicated by heart failure or renal disease 1, 2
• Elevate the head of the bed by 10 degrees during sleep to prevent nocturnal polyuria, maintain favorable fluid distribution, and reduce supine hypertension 1, 2
• Teach physical counter-pressure maneuvers including leg crossing, squatting, stooping, and muscle tensing during symptomatic episodes—these are particularly effective in patients under 60 years with prodromal symptoms 4, 1
• Use compression garments (waist-high compression stockings and abdominal binders) to reduce venous pooling—abdominal binders have strong recommendation based on evidence 1, 5
• Implement acute water ingestion of ≥480 mL for temporary relief, with peak effect at 30 minutes 1
• Recommend smaller, more frequent meals to reduce post-prandial hypotension 1, 2
• Review and discontinue or switch medications that worsen orthostatic hypotension (diuretics, vasodilators, alpha-1 blockers, centrally-acting antihypertensives) rather than simply reducing doses 1, 2

First-Line Pharmacological Options

When non-pharmacological measures fail to adequately control symptoms, choose between:

Midodrine (FDA-Approved, Preferred for Rapid Effect)

• Start at 2.5-5 mg three times daily, increases standing systolic BP by 15-30 mmHg for 2-3 hours 1, 2, 3
• Critical timing: avoid last dose after 6 PM to prevent supine hypertension during sleep 1, 3
• Mechanism: alpha-1 agonist causing arteriolar and venous vasoconstriction 3
• ACC/AHA gives Class IIa recommendation (reasonable to use) for recurrent vasovagal syncope with orthostatic component 4
• Monitor for supine hypertension (can cause systolic BP >200 mmHg), bradycardia, urinary retention 3
• Contraindications: severe heart disease, urinary retention, supine hypertension, pheochromocytoma 3

Fludrocortisone (Traditional First-Line)

• Start at 0.05-0.1 mg once daily, titrate to 0.1-0.3 mg daily (maximum 1.0 mg daily) 1, 2
• Mechanism: mineralocorticoid causing sodium retention and vessel wall effects 1
• American Diabetes Association recommends as first-line for orthostatic hypotension 1
• Major limitation: very low-certainty evidence from small, short-term trials per Cochrane review 6
• Monitor for hypokalemia, supine hypertension, peripheral edema, and heart failure exacerbation 1, 2
• Avoid in patients with active heart failure, severe renal disease, or pre-existing supine hypertension 1

Second-Line and Alternative Agents

Droxidopa (FDA-Approved for Neurogenic Orthostatic Hypotension)

• Particularly effective for neurogenic orthostatic hypotension due to Parkinson's disease, pure autonomic failure, and multiple system atrophy 1, 2
• May reduce falls in these populations 1
• ESC recommends as first-line option alongside midodrine and fludrocortisone 1

Pyridostigmine (For Refractory Cases)

• Consider for elderly patients refractory to other treatments, with fewer side effects than fludrocortisone 1
• ACC/AHA/HRS 2017 guidelines support use in neurogenic orthostatic hypotension refractory to other treatments 1
• Does not cause fluid retention or supine hypertension 1
• Common side effects: nausea, vomiting, abdominal cramping, sweating, salivation 1

Combination Therapy

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

Treatment Algorithm

1. Confirm diagnosis: Measure BP after 5 minutes lying/sitting, then at 1 and 3 minutes after standing (drop ≥20 mmHg systolic or ≥10 mmHg diastolic) 1, 2

2. Identify and eliminate reversible causes: Review medications (especially diuretics, vasodilators, alpha-blockers), assess for volume depletion, evaluate for autonomic neuropathy 1, 2

3. Implement all non-pharmacological measures for 1-2 weeks 1

4. If symptoms persist, initiate pharmacotherapy:

   • For rapid symptom control or neurogenic orthostatic hypotension: Start midodrine 2.5-5 mg TID 1, 3
   • For volume expansion approach or younger patients: Start fludrocortisone 0.05-0.1 mg daily 1, 2
   • For Parkinson's disease or autonomic failure: Consider droxidopa 1, 2

5. Reassess within 1-2 weeks after medication changes 1

6. If inadequate response: Add second agent or switch to alternative 1

7. For refractory cases: Consider pyridostigmine 1

Critical Monitoring and Safety Considerations

• Treatment goal is minimizing postural symptoms, NOT restoring normotension—avoid over-treatment 1, 2
• Monitor for supine hypertension (most important limiting factor)—measure supine BP regularly, especially with midodrine and fludrocortisone 1, 3
• Check electrolytes periodically with fludrocortisone due to potassium wasting 1
• Balance fall risk from orthostatic hypotension against cardiovascular protection—do not aggressively normalize BP 1, 2
• Avoid drug interactions: Do not combine with MAO inhibitors, use caution with other vasoconstrictors (phenylephrine, pseudoephedrine, ephedrine) 3

Common Pitfalls to Avoid

• Do not simply reduce antihypertensive doses—switch to agents with minimal orthostatic effect (long-acting dihydropyridine CCBs or RAS inhibitors preferred) 1, 2
• Do not allow midodrine dosing after 6 PM—this causes nocturnal supine hypertension 1, 3
• Do not use fludrocortisone in heart failure patients—risk of exacerbation 1
• Do not ignore supine hypertension—can cause end-organ damage 1
• Do not use beta-blockers for orthostatic hypotension—ESC gives Class III recommendation (not indicated) 4