What are the guidelines for pharmacotherapy in treating orthostatic (postural) hypotension?

From the Guidelines

Pharmacotherapy for postural hypotension should begin with midodrine (2.5-10 mg three times daily) as the first-line agent, as it directly stimulates alpha-adrenergic receptors to increase vascular tone, according to the most recent and highest quality study 1. The treatment of postural hypotension is challenging, and the therapeutic goal is to minimize postural symptoms rather than to restore normotension.

Non-Pharmacological Measures

In addition to pharmacotherapy, non-pharmacological measures are crucial in managing postural hypotension, including:

• Ensuring adequate salt intake
• Avoiding medications that aggravate hypotension
• Using compressive garments over the legs and abdomen
• Encouraging physical activity and exercise to avoid deconditioning
• Volume repletion with fluids and salt

Pharmacological Measures

For patients with inadequate response to non-pharmacological measures, the following pharmacological agents can be considered:

• Midodrine (2.5-10 mg three times daily) as the first-line agent
• Droxidopa (100-600 mg three times daily) as an add-on therapy, which converts to norepinephrine to improve vascular tone
• Pyridostigmine (30-60 mg three times daily) for patients with mild symptoms, particularly in the morning
• Octreotide (25-100 mcg subcutaneously) for refractory cases, especially for postprandial hypotension

Important Considerations

Treatment should be initiated at low doses and titrated gradually while monitoring for supine hypertension, a common side effect. Medication timing is crucial, and the last dose should be taken at least 4 hours before bedtime to minimize nocturnal hypertension. Patients should be educated about the importance of non-pharmacological measures, including adequate hydration (2-2.5 L daily), salt intake (10-20 g daily), compression garments, and physical countermaneuvers like leg crossing and muscle tensing when changing positions, as recommended by 1.

From the FDA Drug Label

Midodrine hydrochloride tablets are indicated for the treatment of symptomatic orthostatic hypotension (OH) Because midodrine hydrochloride tablets can cause marked elevation of supine blood pressure (BP>200 mmHg systolic), it should be used in patients whose lives are considerably impaired despite standard clinical care, including non-pharmacologic treatment (such as support stockings), fluid expansion, and lifestyle alterations The indication is based on midodrine's effect on increases in 1-minute standing systolic blood pressure, a surrogate marker considered likely to correspond to a clinical benefit.

The guideline for pharmacotherapy for postural hypotension using midodrine includes:

• Indication: Midodrine is indicated for the treatment of symptomatic orthostatic hypotension (OH) in patients whose lives are considerably impaired despite standard clinical care.
• Key considerations:
  • Midodrine can cause marked elevation of supine blood pressure, so it should be used with caution.
  • The treatment should be initiated only in patients who have not responded to non-pharmacologic treatments, such as support stockings, fluid expansion, and lifestyle alterations.
  • Patients should be monitored for supine hypertension and the dose should be adjusted accordingly.
  • Midodrine should be continued only in patients who report significant symptomatic improvement 2.
• Contraindications and precautions:
  • Midodrine should be used with caution in patients with urinary retention problems, diabetes, visual problems, and those taking fludrocortisone acetate.
  • Midodrine should be used with caution in patients with renal impairment, with a starting dose of 2.5 mg, and in patients with hepatic impairment 2.
• Dosage and administration:
  • The dosage of midodrine has not been explicitly stated in the provided text, but it is mentioned that the starting dose for patients with renal impairment should be 2.5 mg 2.
  • Midodrine has been studied in doses of 0,2.5,10, and 20 mg in clinical trials, with the 10 and 20 mg doses producing significant increases in standing systolic blood pressure 2.

From the Research

Guideline for Pharmacotherapy for Postural Hypotension

The following guidelines are based on the available evidence:

• Postural hypotension is defined as a reduction of at least 20 mm Hg in systolic blood pressure or at least a 10 mm Hg decrease in diastolic blood pressure 3.
• The goal of treatment is to make the patient as ambulatory and symptom-free as possible without causing supine hypertension 3.
• A stepped approach starting with nonpharmacologic measures is recommended, with pharmacologic treatment added if necessary 3, 4.
• Fludrocortisone is considered a first- or second-line pharmacological therapy for orthostatic hypotension, alongside mechanical and positional measures 5.
• Midodrine is an effective therapeutic option for the management of various forms of orthostatic hypotension, with similar efficacy to other agents such as dihydroergotamine mesylate and fludrocortisone 6.

Pharmacologic Treatment Options

• Fludrocortisone: increases blood volume and blood pressure, with very low-certainty evidence about its effects on drop in BP and orthostatic symptoms 5.
• Midodrine: a prodrug that increases 1-minute standing systolic blood pressure, improves standing time and energy level, and clinical symptoms of orthostatic hypotension 6.
• Other agents: such as indomethacin and atrial tachypacing may be used in patients who do not respond to first-line treatments 3.

Important Considerations

• The risk of supine hypertension is associated with midodrine therapy, and can be reduced by taking the final daily dose at least 4 hours before bedtime 6.
• There is a lack of information on long-term treatment and treatment of orthostatic hypotension in other disease states 5.
• Education of the patient regarding triggering situations and physiological countermanoeuvers is essential for effective management of orthostatic hypotension 7.