What medications are recommended for a patient with orthostatic hypotension?

Pharmacological Treatment for Orthostatic Hypotension

Midodrine is the first-line pharmacological agent for symptomatic orthostatic hypotension, with the strongest evidence base among pressor agents and FDA approval specifically for this indication. 1, 2

When to Initiate Pharmacological Therapy

Pharmacological treatment should be considered only after non-pharmacological measures (increased fluid intake to 2-3 liters daily, salt intake to 6-9g daily, compression garments, physical counter-maneuvers, head-of-bed elevation) fail to adequately control symptoms. 1 The therapeutic goal is minimizing postural symptoms and improving functional capacity, NOT restoring normotension. 1

First-Line Medication: Midodrine

Start midodrine at 2.5-5 mg three times daily, with the last dose at least 3-4 hours before bedtime (no later than 6 PM) to prevent supine hypertension during sleep. 1, 2

Mechanism and Efficacy

• Midodrine is an alpha-1 adrenergic agonist that increases vascular tone through arteriolar and venous constriction 1
• Can increase standing systolic BP by 15-30 mmHg for 2-3 hours 1
• Three randomized placebo-controlled trials demonstrate efficacy at doses ranging from 5-20mg three times daily 1
• FDA-approved specifically for symptomatic orthostatic hypotension 2

Dosing and Titration

• Initial dose: 2.5-5 mg three times daily 1, 2
• Can be titrated individually up to 10 mg two to four times daily based on response 1
• Dosing should be timed to cover periods when the patient is upright and active 1

Critical Monitoring

• Monitor for supine hypertension (BP >200 mmHg systolic possible) 2
• May cause slight vagal-mediated heart rate slowing 2
• Avoid concomitant use with other vasoconstrictors (phenylephrine, pseudoephedrine, ephedrine) 2
• Use cautiously with cardiac glycosides, beta-blockers, or agents that reduce heart rate 2

Second-Line or Combination Therapy: Fludrocortisone

If midodrine provides insufficient symptom control, add fludrocortisone 0.05-0.1 mg once daily, titrating to 0.1-0.3 mg daily as needed. 1

Mechanism and Efficacy

• Mineralocorticoid that increases plasma volume through sodium retention and vessel wall effects 1
• Evidence quality is limited, with only very low-certainty evidence from small, short-term trials 1, 3
• Can be used as monotherapy or in combination with midodrine for non-responders 1

Dosing

• Initial dose: 0.05-0.1 mg once daily 1
• Titrate individually to 0.1-0.3 mg daily 1
• Maximum dose: 1.0 mg daily 1
• Alternative loading approach: 0.2 mg loading dose followed by 0.1 mg daily maintenance 1

Critical Contraindications and Monitoring

• Avoid in patients with active heart failure, significant cardiac dysfunction, pre-existing supine hypertension, or severe renal disease 1
• Monitor for supine hypertension (most important limiting factor) 1
• Check electrolytes periodically for hypokalemia due to mineralocorticoid effects 1
• Monitor for peripheral edema and congestive heart failure 1
• Requires adequate salt intake (6-9g daily) to be effective 1

Alternative First-Line Option: Droxidopa

Droxidopa is FDA-approved and particularly effective for neurogenic orthostatic hypotension in Parkinson's disease, pure autonomic failure, and multiple system atrophy. 1, 4

• May reduce falls in these specific populations 1
• Effectiveness beyond 2 weeks has not been established; continued effectiveness should be assessed periodically 4
• Can improve symptoms in neurogenic orthostatic hypotension due to dopamine beta-hydroxylase deficiency and non-diabetic autonomic neuropathy 4

Refractory Cases: Pyridostigmine

For elderly patients with refractory orthostatic hypotension who have failed first-line treatments, particularly those with concurrent supine hypertension, consider pyridostigmine 60 mg orally three times daily. 1

Advantages Over Other Agents

• Does NOT worsen supine hypertension (unlike midodrine, fludrocortisone, and droxidopa) 1
• Does NOT cause fluid retention (safer in patients with cardiac dysfunction) 1
• Favorable side effect profile compared to alternatives 1
• Works by inhibiting acetylcholinesterase, enhancing ganglionic sympathetic transmission 1

Dosing and Side Effects

• Starting dose: 60 mg orally three times daily 1
• Maximum dose: 600 mg daily 1
• Common side effects: nausea, vomiting, abdominal cramping, sweating, salivation, urinary incontinence (generally manageable) 1

Critical Medication Review

Before initiating any pressor agent, discontinue or switch medications that worsen orthostatic hypotension—do NOT simply reduce doses. 1, 5

Medications to Discontinue or Switch

• Alpha-1 blockers (doxazosin, prazosin, terazosin, tamsulosin): most problematic in older adults 1, 5
• Diuretics: most frequent cause of drug-induced orthostatic hypotension 1, 5
• Centrally-acting agents (clonidine, methyldopa) 5
• Vasodilators (hydralazine, minoxidil) 5
• Beta-blockers: avoid unless compelling indications exist 1, 5

Preferred Antihypertensives if BP Control Still Needed

• Long-acting dihydropyridine calcium channel blockers (amlodipine) 1, 5
• RAS inhibitors (ACE inhibitors or ARBs) 1, 5

Monitoring Protocol

Measure blood pressure after 5 minutes of sitting/lying, then at 1 and 3 minutes after standing at each visit. 1

• Early review at 24-48 hours after medication initiation 6
• Reassess within 1-2 weeks after medication changes 1
• Monitor both standing BP (for efficacy) and supine BP (for safety) 1
• Assess standing heart rate, blood pressure, and symptom improvement 6

Common Pitfalls to Avoid

• Do NOT administer midodrine after 6 PM (causes nocturnal supine hypertension) 1, 2
• Do NOT use fludrocortisone in patients with heart failure or supine hypertension 1
• Do NOT simply reduce doses of offending medications—switch to alternatives 1, 5
• Do NOT combine multiple vasoconstrictors without careful BP monitoring 6, 2
• Do NOT overlook volume depletion as a contributing factor 1
• Do NOT aim for normotension—goal is symptom control 1

Special Populations

Patients with Concurrent Supine Hypertension

• Pyridostigmine is preferred (does not worsen supine BP) 1
• If using midodrine or fludrocortisone, prevent patient from becoming fully supine by elevating head of bed 10 degrees 1

Patients with Cardiac Dysfunction

• Avoid fludrocortisone (causes fluid retention) 1
• Pyridostigmine is safer alternative 1

Patients with Bradycardia

• Midodrine may cause slight vagal-mediated heart rate slowing, but benefits usually outweigh concerns 6, 2
• Cardiac pacing is NOT recommended for orthostatic hypotension with bradycardia unless documented intrinsic sinus node dysfunction exists 6