What are the treatment options for neurogenic orthostatic hypotension?

Treatment Options for Neurogenic Orthostatic Hypotension

Droxidopa is the most effective pharmacological treatment for neurogenic orthostatic hypotension, with strong evidence supporting its use for improving symptoms of orthostatic dizziness, lightheadedness, and preventing syncope. 1

First-Line Non-Pharmacological Interventions

Non-pharmacological measures should be implemented before or alongside medication:

1. Acute water ingestion

   • Recommended for temporary relief of symptoms 2
   • Drink 500ml of water 30 minutes before meals or anticipated orthostatic stress

2. Physical counter-pressure maneuvers

   • Beneficial for preventing syncope 2
   • Techniques include leg crossing, squatting, and muscle tensing

3. Compression garments

   • Thigh-high compression stockings and abdominal binders 2, 3
   • Should provide at least 30-40 mmHg of pressure

4. Dietary modifications

   • Increased salt intake (6-10g daily) 2, 3
   • Increased fluid intake (2-3 liters per day) 3
   • Small, frequent meals with reduced carbohydrate content 3
   • Delaying fluid intake until 30 minutes after meals 3

Pharmacological Treatment Algorithm

First-Line Medications:

1. Droxidopa (100-600mg TID)

   • FDA-approved specifically for neurogenic orthostatic hypotension 1
   • Directly metabolized to norepinephrine, increasing blood pressure through peripheral vasoconstriction 1
   • Strong recommendation with high-quality evidence 2
   • Dosing: Start at 100mg TID, titrate by 100mg increments every 24-48 hours to maximum 600mg TID
   • Take last dose at least 3 hours before bedtime to avoid supine hypertension

2. Midodrine (5-20mg TID)

   • Alpha-1 adrenergic agonist causing arterial and venous vasoconstriction 2, 3
   • Strong recommendation with high-quality evidence 2
   • Dosing: Start at 5mg TID, titrate up to 20mg TID
   • Schedule doses for when upright position is needed (morning, midday, late afternoon)
   • Last dose should be at least 4 hours before bedtime

Second-Line Medications:

1. Fludrocortisone (0.1-0.3mg daily)

   • Salt-retaining steroid that expands plasma volume 2, 3
   • Moderate recommendation with lower quality evidence 2
   • Monitor for supine hypertension, edema, hypokalemia, and headache

2. Pyridostigmine (30mg 2-3 times daily)

   • Acetylcholinesterase inhibitor that improves orthostatic tolerance 2, 3
   • Consider for patients refractory to other treatments 2
   • May be better tolerated in patients prone to supine hypertension

Third-Line Medications:

1. Octreotide
   • Beneficial in patients with refractory neurogenic OH 2
   • Particularly useful for postprandial hypotension 3, 4
   • Reduces splanchnic blood pooling after meals

Special Considerations

Monitoring and Follow-up

• Regular blood pressure monitoring in both supine and standing positions
• Monitor for supine hypertension (BP>180/110 mmHg)
• Assess treatment efficacy based on symptom improvement rather than absolute BP values
• For patients on fludrocortisone, monitor serum potassium levels

Supine Hypertension Management

• Elevate head of bed 30 degrees at night
• Consider short-acting antihypertensives at bedtime if severe
• Avoid taking vasopressors within 4 hours of bedtime

High-Risk Populations

• Elderly patients (≥75 years): No dose adjustment needed for droxidopa, but monitor closely 1
• Renal impairment: Limited data for severe renal impairment (GFR<30 mL/min) 1
• Parkinson's disease patients: May require lower initial doses of medications
• Patients with cardiac disease: Monitor closely for supine hypertension

Treatment Pitfalls to Avoid

1. Focusing on BP numbers rather than symptoms

   • The goal is to reduce orthostatic symptoms and improve quality of life, not normalize BP

2. Overlooking non-pharmacological measures

   • Physical countermeasures and compression garments are highly effective and should always be implemented

3. Improper timing of medications

   • Administering vasopressors too close to bedtime increases risk of supine hypertension

4. Failure to discontinue contributing medications

   • Many medications can worsen orthostatic hypotension (antihypertensives, antipsychotics, diuretics)

5. Inadequate monitoring for supine hypertension

   • All pharmacological treatments can cause or worsen supine hypertension

The evidence strongly supports a structured approach to neurogenic orthostatic hypotension, starting with non-pharmacological measures and adding pharmacological therapy when needed, with droxidopa and midodrine having the strongest evidence base for efficacy 2, 1, 4.