What are the treatment options for a patient with 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 lifestyle modifications. 1

Step 1: Identify and Eliminate Reversible Causes

• Discontinue or switch medications that worsen orthostatic hypotension rather than simply reducing doses 1
• Drug-induced autonomic failure is the most frequent cause of orthostatic hypotension, with diuretics and vasodilators being the primary culprits 1
• Alpha-1 blockers (doxazosin, prazosin, terazosin), centrally-acting agents (clonidine, methyldopa), and psychotropic medications commonly cause orthostatic symptoms 1, 2
• Evaluate for volume depletion, endocrine disorders, and neurogenic causes 1
• Avoid alcohol, as it induces both autonomic neuropathy and central volume depletion 1

Step 2: Implement Non-Pharmacological Measures (First-Line for All Patients)

Volume Expansion

• Increase fluid intake to 2-3 liters daily 1
• Increase 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

Postural Modifications

• Elevate the head of bed by 10 degrees during sleep to prevent nocturnal polyuria, maintain favorable fluid distribution, and reduce supine hypertension 1
• Teach gradual staged movements with postural changes 1
• Implement physical counter-maneuvers during symptomatic episodes: leg crossing, squatting, stooping, and muscle tensing (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

Dietary Modifications

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

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

The therapeutic goal is minimizing postural symptoms rather than restoring normotension. 1

First-Line Pharmacological Options

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 1
• Can increase standing systolic BP by 15-30 mmHg for 2-3 hours 1
• Take the last dose 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 1
• 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, hypokalemia, congestive heart failure, and peripheral edema 1
• Avoid in patients with active heart failure, significant cardiac dysfunction, pre-existing supine hypertension, or severe renal disease 1
• Check electrolytes periodically due to potassium wasting 1

Droxidopa

• FDA-approved for neurogenic orthostatic hypotension caused by Parkinson's disease, multiple system atrophy, pure autonomic failure, dopamine beta-hydroxylase deficiency, and non-diabetic autonomic neuropathy 3
• Effectiveness beyond 2 weeks has not been established; assess continued effectiveness periodically 3
• Particularly effective for neurogenic orthostatic hypotension and may reduce falls 1
• In clinical trials, showed a statistically significant 0.9 unit decrease in dizziness at Week 1 versus placebo (P=0.028), but the 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 1
• These agents work through complementary mechanisms (alpha-1 adrenergic stimulation vs. sodium retention) 1

Pyridostigmine

• Consider for refractory orthostatic hypotension in elderly patients who have not responded to other treatments 1
• Has a favorable side effect profile compared to alternatives like fludrocortisone 1
• Common side effects include nausea, vomiting, abdominal cramping, sweating, salivation, and urinary incontinence 1

Step 4: Special Considerations

Patients with Concurrent Hypertension and Orthostatic Hypotension

• Use long-acting dihydropyridine calcium channel blockers or RAS inhibitors as first-line antihypertensive therapy 1, 2
• These agents have minimal impact on orthostatic blood pressure 2
• Switch medications that worsen orthostatic hypotension to alternatives rather than reducing doses 1
• Avoid beta-blockers unless compelling indications exist 2

Diabetic Patients

• Assess for cardiovascular autonomic neuropathy 1
• Consider alpha-lipoic acid for painful diabetic neuropathy, which may benefit autonomic function 1

Monitoring Protocol

• Measure blood pressure after 5 minutes of sitting/lying, then at 1 and 3 minutes after standing 1
• Monitor for both symptomatic improvement and development of supine hypertension 1
• Reassess within 1-2 weeks after medication changes 1
• Regular monitoring for adverse effects is essential, especially supine hypertension with pressor agents and electrolyte abnormalities with fludrocortisone 1

Critical Pitfalls to Avoid

• Do not simply reduce the dose of offending medications—switch to alternatives 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
• Balance the benefits of increasing standing blood pressure against the risk of worsening supine hypertension 1