What are the treatment options for orthostatic hypotension?

Treatment of Orthostatic Hypotension

Begin with non-pharmacological interventions for all patients, and add pharmacological therapy only when symptoms persist despite these measures, with midodrine as the first-line medication and fludrocortisone as an alternative or adjunct. 1

Initial Evaluation and Reversible Causes

Before initiating treatment, measure blood pressure after 5 minutes of sitting/lying, then at 1 and/or 3 minutes after standing to confirm the diagnosis 1. The most critical first step is identifying and discontinuing medications that cause orthostatic hypotension, as drug-induced autonomic failure is the most frequent cause. 1

High-Risk Medications to Discontinue or Switch:

• Alpha-1 blockers (doxazosin, prazosin, terazosin, tamsulosin) are strongly associated with orthostatic hypotension, especially in older adults 1, 2
• Diuretics cause orthostatic hypotension through volume depletion and are "probably the most frequent cause" overall 1, 2
• Centrally-acting antihypertensives (clonidine, methyldopa) 2
• Vasodilators (hydralazine, minoxidil) 1

Switch these medications to alternatives rather than simply reducing the dose 1. For patients requiring continued antihypertensive therapy, long-acting dihydropyridine calcium channel blockers or RAS inhibitors are preferred as they have minimal impact on orthostatic blood pressure 2.

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

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—particularly effective in patients under 60 years with prodromal symptoms 1
• Use waist-high compression stockings (30-40 mmHg) and abdominal binders to reduce venous pooling 1

Positional Strategies:

• Elevate the head of the 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:

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

Pharmacological Management (When Non-Pharmacological Measures Fail)

The therapeutic goal is minimizing postural symptoms and improving functional capacity, not restoring normotension. 1

First-Line Pharmacological Therapy:

Midodrine (FDA-approved, strongest evidence base):

• Initial dose: 2.5-5 mg three times daily 1, 3
• Timing: Last dose at least 3-4 hours before bedtime (avoid after 6 PM) to prevent supine hypertension 1, 3
• Mechanism: Alpha-1 agonist causing arteriolar and venous constriction 3
• Effect: Increases standing systolic BP by 15-30 mmHg for 2-3 hours 1, 3
• Evidence: Three randomized placebo-controlled trials demonstrate efficacy 1
• Monitoring: Watch for supine hypertension (BP >200 mmHg systolic can occur) 3

Alternative or Adjunct First-Line Therapy:

Fludrocortisone:

• Initial dose: 0.05-0.1 mg once daily 1
• Titration: Increase to 0.1-0.3 mg daily as needed (maximum 1.0 mg daily) 1
• Mechanism: Mineralocorticoid causing sodium retention and vessel wall effects 1
• Contraindications: Active heart failure, significant cardiac dysfunction, severe renal disease, pre-existing supine hypertension 1
• Monitoring: Check for supine hypertension (most important limiting factor), monitor electrolytes periodically for hypokalemia, watch for peripheral edema and congestive heart failure 1
• Evidence quality: Limited, with only very low-certainty evidence from small, short-term trials 1

Combination Therapy:

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

Additional Pharmacological Options:

Droxidopa (FDA-approved):

• Particularly effective for neurogenic orthostatic hypotension in Parkinson's disease, pure autonomic failure, and multiple system atrophy 1
• May reduce falls 1

Pyridostigmine:

• Consider for refractory orthostatic hypotension when other treatments fail 1
• Favorable side effect profile compared to alternatives—does not cause fluid retention or supine hypertension 1, 2
• Common side effects: nausea, vomiting, abdominal cramping, sweating, salivation, urinary incontinence 1

Critical Monitoring Requirements

• Measure blood pressure supine and standing at each visit to balance symptom improvement against supine hypertension risk 1
• Supine hypertension can cause end-organ damage—this is the most important limiting factor with pressor agents 1
• Monitor electrolytes periodically with fludrocortisone due to potassium wasting 1
• Reassess within 1-2 weeks after medication changes 1

Special Populations

Patients with Both Hypertension and Orthostatic Hypotension:

• Test for orthostatic hypotension before starting or intensifying any blood pressure-lowering medication 1, 2
• Prefer long-acting dihydropyridine calcium channel blockers or RAS inhibitors as first-line antihypertensive therapy 1, 2
• Avoid beta-blockers unless compelling indications exist 2

Diabetic Patients:

• Assess for cardiovascular autonomic neuropathy 1
• Consider pyridostigmine as it does not cause fluid retention or supine hypertension 2

Elderly/Frail Patients:

• Start with lower doses (midodrine 2.5 mg if renal impairment) 1, 3
• Particularly vulnerable to thiazide-induced orthostatic hypotension 2

Common Pitfalls to Avoid

• Do not simply reduce the dose of offending medications—switch to alternatives 1
• Do not allow patients to take midodrine if they will be supine for extended periods 3
• Do not use fludrocortisone in patients with heart failure or supine hypertension 1
• Do not combine midodrine with other vasoconstrictors (phenylephrine, pseudoephedrine, ephedrine) without careful blood pressure monitoring 3
• Do not use alpha-adrenergic blocking agents (prazosin, terazosin, doxazosin) as they antagonize midodrine's effects 3