What are the treatment options for neurogenic orthostatic hypotension (NOH)?

Treatment of Neurogenic Orthostatic Hypotension

Begin with non-pharmacological measures first, then add midodrine or droxidopa as first-line pharmacological agents, with fludrocortisone as an alternative or combination therapy when monotherapy fails. 1

Initial Management: Non-Pharmacological Interventions

Before initiating medications, implement these evidence-based strategies:

Medication Review and Optimization

• Discontinue or minimize drugs that exacerbate orthostatic hypotension, including psychotropic drugs, diuretics, and α-adrenoreceptor antagonists 1
• Identify and correct volume depletion 1

Physical Maneuvers and Positioning

• Physical counter-pressure maneuvers (leg crossing, squatting, lower body muscle tensing) can acutely increase blood pressure, with squatting producing the largest effect 1
• Elevate the head of the bed during sleep to reduce supine hypertension risk 1, 2
• Teach gradual staged movements with postural changes 1

Compression Therapy

• Use compression garments that are at least thigh-high and preferably include the abdomen—shorter garments are ineffective 1
• These garments improve orthostatic symptoms and blunt blood pressure decreases 1

Hydration and Dietary Modifications

• Acute water ingestion (≥480 mL) provides temporary relief with peak effect at 30 minutes 1
• Increase salt intake to 6-9 g (100-150 mmol; approximately 1-2 teaspoons) daily if not contraindicated 1
• Avoid large carbohydrate-rich meals that can worsen postprandial hypotension 1

Important caveat: Salt and fluid supplementation may not be appropriate for patients with hypertension, renal disease, heart failure, or cardiac dysfunction 1

Pharmacological Treatment

First-Line Agents

Midodrine is the FDA-approved first-line medication for neurogenic orthostatic hypotension 1:

• Dosing: Start with 10 mg three times daily (upon arising, midday, and late afternoon at least 3 hours before bedtime) 1, 3
• Can titrate up to 10 mg two to four times daily based on response 1
• Mechanism: Peripheral selective α1-adrenergic agonist causing arteriolar and venous constriction 1, 4
• Efficacy: Produces a 22 mmHg increase in standing systolic blood pressure with significant symptom improvement 1, 3, 5
• Side effects: Pilomotor reactions (scalp tingling), pruritus, supine hypertension, bradycardia, gastrointestinal symptoms, and urinary retention 1

Droxidopa is an alternative first-line agent 1, 2:

• Dosing: Start with 100 mg three times daily (morning, midday, late afternoon at least 3 hours before bedtime), titrate in 100 mg increments every 24-48 hours up to maximum 600 mg three times daily 2
• Take consistently with or without food; swallow capsules whole 2
• Efficacy: Improves symptoms in Parkinson disease, pure autonomic failure, and multiple system atrophy; may reduce falls 1
• Side effects: Supine hypertension, headache, dizziness, nausea 1, 2
• Important interaction: Carbidopa may decrease droxidopa effectiveness in Parkinson patients 1

Second-Line Agent

Fludrocortisone is another first-choice option, particularly when supine hypertension is not present 1:

• Dosing: Start 0.05-0.1 mg daily, titrate to 0.1-0.3 mg daily 1
• Mechanism: Sodium retention, direct vasoconstriction on partially denervated vessels, increased vessel wall water content 1
• Side effects: Supine hypertension, hypokalemia, congestive heart failure, peripheral edema 1
• Critical warning: When supine hypertension is present, use other medications before fludrocortisone; doses >0.3 mg daily risk adrenal suppression and immunosuppression 1

Combination Therapy

• Use fludrocortisone combined with midodrine or droxidopa in patients who do not respond to monotherapy 1

Refractory Cases: Third-Line Options

Pyridostigmine

• May be beneficial in refractory neurogenic orthostatic hypotension 1
• Improves orthostatic tolerance through increased peripheral vascular resistance 1
• Side effects: nausea, vomiting, abdominal cramping, sweating, salivation, urinary incontinence 1

Octreotide

• Consider for refractory recurrent postprandial or neurogenic orthostatic hypotension 1
• Reduces splanchnic blood flow by approximately 20%, preventing postprandial hypotension 1

Other Agents (Limited Evidence)

• Erythropoietin: For diabetic patients with hemoglobin <11 g/dL, dose 25-75 U/kg three times weekly subcutaneously or intravenously, target hemoglobin 12 g/dL 1
• Desmopressin acetate: Useful for nocturnal polyuria and morning orthostatic hypotension 1
• Caffeine and acarbose: May attenuate postprandial hypotension 1

Critical Management Principles

The therapeutic goal is to minimize postural symptoms, not to restore normotension 1. Balance the benefit of increasing standing blood pressure against the risk of supine hypertension 1.

Monitoring Requirements

• Monitor supine blood pressure before initiating therapy and after each dose increase, particularly in the recommended head-elevated sleeping position 1, 2
• If supine hypertension persists despite head elevation, reduce or discontinue the offending agent 2
• Assess continued effectiveness periodically—effectiveness beyond 2 weeks has not been established for droxidopa 2

Common Pitfall

Supine hypertension is the major limiting factor for all pharmacological treatments and increases stroke risk if not well-managed 1, 2. Always measure blood pressure in both supine and head-elevated positions.