What are the treatments for orthostatic hypotension?

Treatment of Orthostatic Hypotension

The treatment of orthostatic hypotension should begin with discontinuing or switching offending medications and implementing non-pharmacologic measures (increased fluid/salt intake, compression garments, physical counter-maneuvers), followed by pharmacologic therapy with midodrine or fludrocortisone as first-line agents when non-pharmacologic measures fail to adequately control symptoms. 1

Treatment Goals

• The therapeutic objective is minimizing postural symptoms and improving functional capacity rather than restoring normotension—this is critical to avoid causing supine hypertension while treating orthostatic symptoms. 2, 1
• Treatment should focus on improving the patient's ability to perform activities of daily living and reducing fall risk. 3

Step 1: Identify and Eliminate Reversible Causes

• Medication review is the mandatory first step—drug-induced autonomic failure is the most frequent cause of orthostatic hypotension, with diuretics and vasodilators being the most important culprits. 1
• Discontinue or switch (rather than simply reduce the dose) medications that worsen orthostatic hypotension, including: 1, 4
  • Alpha-1 blockers (doxazosin, prazosin, terazosin, tamsulosin)
  • Centrally-acting antihypertensives (clonidine, methyldopa, guanfacine)
  • Diuretics causing volume depletion
  • Vasodilators (hydralazine, minoxidil)
  • Psychotropic medications
• For patients requiring continued antihypertensive therapy, switch to long-acting dihydropyridine calcium channel blockers or RAS inhibitors (ACE inhibitors/ARBs), which have minimal impact on orthostatic blood pressure. 1, 5
• Assess for volume depletion, anemia, and endocrine disorders (adrenal insufficiency, hypothyroidism). 1

Step 2: Non-Pharmacologic Interventions (First-Line for All Patients)

Volume Expansion

• Increase fluid intake to 2-3 liters daily (unless contraindicated by heart failure). 1
• Increase salt consumption to 6-9 grams daily (if not contraindicated by heart failure or hypertension). 2, 1
• Acute water ingestion of ≥480 mL provides temporary relief with peak effect at 30 minutes—useful before activities that provoke symptoms. 1

Physical Counter-Maneuvers

• Teach leg crossing, squatting, stooping, and muscle tensing during symptomatic episodes—these are particularly effective in patients under 60 years with prodromal symptoms. 1
• These maneuvers should be implemented at the first sign of symptoms to prevent syncope. 1

Compression Garments

• Use waist-high compression stockings (30-40 mmHg) and abdominal binders to reduce venous pooling in the lower extremities and splanchnic circulation. 1

Postural Modifications

• 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—avoid rapid standing. 1

Dietary Modifications

• Eat smaller, more frequent meals to reduce post-prandial hypotension, which can be as significant as orthostatic drops. 2, 1
• Avoid large carbohydrate-rich meals and limit alcohol consumption. 1, 6

Physical Conditioning

• Encourage physical activity and exercise to avoid deconditioning, which exacerbates orthostatic intolerance—this is a common pitfall where patients become sedentary due to symptoms, worsening the condition. 2, 1

Step 3: Pharmacologic Treatment (When Non-Pharmacologic Measures Insufficient)

First-Line Pharmacologic Agents

Midodrine (Strongest Evidence Base)

• Midodrine is the first-line pharmacologic agent with the strongest evidence, supported by three randomized placebo-controlled trials and FDA approval. 1, 7
• Dosing: Start at 2.5-5 mg three times daily, can increase standing systolic BP by 15-30 mmHg for 2-3 hours. 1
• Critical timing: Avoid taking the last dose after 6 PM (ideally last dose at least 3-4 hours before bedtime) to prevent supine hypertension during sleep. 1
• Mechanism: Peripheral selective α1-adrenergic agonist causing arteriolar and venous constriction. 1
• FDA indication: For symptomatic orthostatic hypotension in patients whose lives are considerably impaired despite standard clinical care. 7

Fludrocortisone

• Dosing: Start at 0.05-0.1 mg once daily, titrate individually to 0.1-0.3 mg daily (maximum 1.0 mg daily). 2, 1
• Mechanism: Mineralocorticoid that acts through sodium retention and vessel wall effects. 2, 1
• Monitoring requirements: 1
  • Check for supine hypertension (most important limiting factor)
  • Monitor electrolytes periodically for hypokalemia
  • Assess for peripheral edema and signs of heart failure
• Contraindications: Active heart failure, significant cardiac dysfunction, severe renal disease, pre-existing supine hypertension. 1
• Evidence quality is limited (very low-certainty evidence from small, short-term trials), but it remains a guideline-recommended first-line option. 1

Droxidopa

• FDA-approved for neurogenic orthostatic hypotension, particularly effective for Parkinson's disease, pure autonomic failure, and multiple system atrophy. 2, 1
• May reduce falls in these populations. 1

Combination Therapy

• For non-responders to monotherapy, consider combination therapy with midodrine and fludrocortisone. 1

Second-Line and Refractory Cases

Pyridostigmine

• Beneficial for refractory orthostatic hypotension in elderly patients who have not responded to first-line treatments. 1
• Advantages: Favorable side effect profile compared to fludrocortisone—does not cause fluid retention or supine hypertension. 1
• Supported by 2017 ACC/AHA/HRS guidelines for neurogenic orthostatic hypotension refractory to other treatments. 1
• Common side effects: Nausea, vomiting, abdominal cramping, sweating, salivation, urinary incontinence (generally manageable). 1

Other Agents for Specific Situations

• Erythropoietin: Consider for patients with anemia and severe autonomic neuropathy. 1
• Desmopressin acetate: May correct nocturnal polyuria and morning orthostatic hypotension. 1
• Atomoxetine: Case reports suggest efficacy in elderly patients with primary orthostatic hypotension refractory to standard therapies. 6

Step 4: Management of Concurrent Supine Hypertension

• Supine blood pressure tends to be much higher in patients with orthostatic hypotension, creating a treatment challenge. 2
• Use shorter-acting antihypertensives at bedtime to manage supine hypertension without worsening morning orthostatic symptoms: 2, 1
  • Shorter-acting calcium blockers (isradipine)
  • Shorter-acting β-blockers (atenolol, metoprolol tartrate)
  • Agents affecting baroreceptor activity (guanfacine, clonidine)
  • Enalapril as an alternative if patients cannot tolerate preferred agents

Monitoring and Follow-Up

• Measure blood pressure after 5 minutes lying/sitting, then at 1 and 3 minutes after standing to document orthostatic changes and assess treatment response. 1
• Monitor for both symptomatic improvement and development of supine hypertension—this is the critical balance in treatment. 1
• Reassess within 1-2 weeks after medication changes. 1
• Continue midodrine only for patients who report significant symptomatic improvement, as per FDA labeling. 7

Common Pitfalls to Avoid

• Do not simply reduce the dose of offending antihypertensives—switch to alternative agents with less orthostatic effect instead. 1
• Avoid beta-blockers in patients with orthostatic hypotension unless there are compelling indications (e.g., heart failure with reduced ejection fraction, recent MI). 1, 5
• Do not overlook deconditioning—patients often become sedentary due to symptoms, which paradoxically worsens orthostatic intolerance. 2, 1
• Remember that treating to normotension is not the goal—overly aggressive treatment increases the risk of supine hypertension and end-organ damage. 1
• Do not use fludrocortisone in patients with heart failure or significant supine hypertension—the risks outweigh benefits. 1