What is the best treatment approach for orthostatic hypotension in an older patient with Parkinson's disease (PD), considering potential comorbidities and medication interactions, using fludrocortisone (a mineralocorticoid)?

Treatment of Orthostatic Hypotension in Parkinson's Disease with Fludrocortisone

Fludrocortisone is a reasonable second-line pharmacological option for orthostatic hypotension in Parkinson's disease, but midodrine should be considered first-line due to stronger evidence, with fludrocortisone reserved for combination therapy or when midodrine is contraindicated. 1

Initial Non-Pharmacological Management (Always Start Here)

Before initiating any medication, implement these measures which form the foundation of treatment:

• Increase fluid intake to 2-3 liters daily and salt intake to 6-9 grams daily (unless contraindicated by heart failure or other cardiac conditions) 1
• Elevate the head of the bed by 10 degrees during sleep to prevent nocturnal polyuria and reduce supine hypertension 1
• Teach physical counter-pressure maneuvers including leg crossing, squatting, stooping, and muscle tensing during symptomatic episodes 1
• Use compression garments (waist-high stockings 30-40 mmHg or abdominal binders) to reduce venous pooling 1
• Recommend smaller, more frequent meals to reduce postprandial hypotension 2, 1
• Encourage physical activity and exercise to avoid deconditioning, which worsens orthostatic intolerance 2, 1

Medication Review (Critical First Step)

Discontinue or switch medications that worsen orthostatic hypotension rather than simply reducing doses—this is the most frequent reversible cause 1:

• Alpha-1 blockers (doxazosin, prazosin, terazosin, tamsulosin) 1
• Diuretics 1
• Vasodilators 1
• Avoid combining multiple vasodilating agents (ACE inhibitors + calcium channel blockers + diuretics) without careful monitoring 1

Pharmacological Treatment Algorithm

First-Line: Midodrine

Midodrine has the strongest evidence base among pressor agents with three randomized placebo-controlled trials demonstrating efficacy 1:

• Start at 2.5-5 mg three times daily, taken at approximately 4-hour intervals during daytime hours 1, 3
• Titrate up to 10 mg three times daily based on response 1
• Last dose must be taken at least 3-4 hours before bedtime (not after 6 PM) to prevent supine hypertension during sleep 1
• Increases standing systolic BP by 15-30 mmHg for 2-3 hours 1

Second-Line or Combination: Fludrocortisone

If midodrine alone provides insufficient symptom control or is contraindicated, add or switch to fludrocortisone 1:

• Start at 0.05-0.1 mg once daily 1
• Titrate to 0.1-0.3 mg daily based on individual response 1
• Maximum dose is 1.0 mg daily 1
• Acts through sodium retention and vessel wall effects 1

Combination Therapy for Refractory Cases

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

• Midodrine provides acute pressor effect 1
• Fludrocortisone provides volume expansion 1

Alternative: Droxidopa

Droxidopa is FDA-approved and particularly effective for neurogenic orthostatic hypotension in Parkinson's disease 1:

• May reduce falls 1
• Can improve symptoms in neurogenic orthostatic hypotension due to Parkinson's disease, pure autonomic failure, and multiple system atrophy 1

Critical Monitoring Requirements for Fludrocortisone

Monitor for these adverse effects regularly 1, 4:

• Supine hypertension (most important limiting factor—measure both supine and standing BP at each visit) 1
• Hypokalemia (check electrolytes periodically due to mineralocorticoid effects) 1
• Peripheral edema 1
• Congestive heart failure exacerbation 1

Absolute Contraindications to Fludrocortisone

Do not use fludrocortisone in patients with 1, 4:

• Active heart failure or significant cardiac dysfunction 1
• Pre-existing severe supine hypertension 1
• Severe renal disease where sodium retention would be harmful 1

Special Considerations in Elderly Parkinson's Patients

Elderly subjects commonly have conditions exacerbated by fludrocortisone therapy including hypertension, edema, hypokalemia, congestive heart failure, cataracts, glaucoma, increased intraocular pressure, renal insufficiency, and osteoporosis 4:

• Start at the low end of the dosing range (0.05 mg daily) 4
• Monitor for drug interactions with digitalis glycosides, oral anticoagulants, antidiabetic drugs, and aspirin 4

Treatment Goals and Monitoring Schedule

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

• Measure BP after 5 minutes lying/sitting, then at 1 and 3 minutes after standing 1
• Reassess within 1-2 weeks after medication changes 1
• Monitor orthostatic vital signs at each follow-up visit 1
• Continue medication only if symptomatic improvement is demonstrated 1

Evidence Quality for Fludrocortisone

The evidence for fludrocortisone in Parkinson's disease is limited 5:

• Very low-certainty evidence from small, short-term studies (2-3 weeks) 5
• One cross-over RCT in 9 Parkinson's patients showed fludrocortisone had less diastolic BP improvement than pyridostigmine (-14 mmHg vs -22.1 mmHg; P=0.036) 5
• Orthostatic symptoms remained unchanged in this study 5
• One older study from 1975 showed fludrocortisone 0.05-0.2 mg daily effectively treated levodopa-induced postural hypotension in 6 patients over 6-10 months with no adverse reactions 6

Common Pitfalls to Avoid

• Do not simply reduce the dose of offending medications—switch to alternative therapy 1
• Do not administer midodrine after 6 PM 1
• Do not use fludrocortisone in patients with heart failure or supine hypertension 1
• Do not overlook volume depletion as a contributing factor 1
• Do not combine multiple vasodilating agents without careful monitoring 1