What medications are used to treat orthostatic hypotension?

From the Guidelines

Midodrine and droxidopa are the most effective medications for treating orthostatic hypotension, as they are approved by the FDA and have been shown to improve symptoms in clinical studies. According to the most recent and highest quality study 1, midodrine and droxidopa are recommended for the treatment of orthostatic hypotension. Midodrine is usually prescribed at 2.5-10 mg three times daily and works as an alpha-1 agonist to constrict blood vessels, while droxidopa is dosed at 100-600 mg three times daily and converts to norepinephrine to increase blood pressure.

Other options for treating orthostatic hypotension include:

• Fludrocortisone, which increases sodium retention and expands blood volume
• Pyridostigmine, which enhances sympathetic activation upon standing
• Caffeine, which can provide a quick blood pressure boost
• NSAIDs like indomethacin, which inhibit prostaglandin synthesis to raise blood pressure

Non-pharmacological measures, such as increased salt and fluid intake, compression stockings, and avoiding rapid position changes, are also important for managing orthostatic hypotension. Treatment should be individualized based on symptom severity, with the goal of reducing symptoms rather than normalizing blood pressure readings. As noted in 1, physical activity and exercise should be encouraged to avoid deconditioning, which is known to exacerbate orthostatic intolerance, and volume repletion with fluids and salt is critical.

In addition to these measures, the study 1 also suggests that supine blood pressure tends to be much higher in patients with orthostatic hypotension, often requiring treatment of blood pressure at bedtime with shorter-acting drugs. Alternatives can include enalapril if patients are unable to tolerate preferred agents.

It's worth noting that the treatment of orthostatic hypotension can be challenging, and the therapeutic goal is to minimize postural symptoms rather than to restore normotension, as stated in 1 and 1. Therefore, a thorough balance between the goal of increasing standing blood pressure and the avoidance of a marked increase in supine blood pressure is necessary, as noted in 1.

From the FDA Drug Label

Midodrine hydrochloride tablets are indicated for the treatment of symptomatic orthostatic hypotension (OH) Midodrine forms an active metabolite, desglymidodrine, that is an alpha1-agonist, and exerts its actions via activation of the alpha-adrenergic receptors of the arteriolar and venous vasculature, producing an increase in vascular tone and elevation of blood pressure. The medication used to treat orthostatic hypotension is midodrine.

• Key points:
  • Midodrine is an alpha1-agonist that increases vascular tone and blood pressure.
  • It is indicated for the treatment of symptomatic orthostatic hypotension.
  • The medication should be used with caution in certain patients, such as those with supine hypertension, renal impairment, or hepatic impairment. 2 2 2

From the Research

Medications for Orthostatic Hypotension

The following medications are used to treat orthostatic hypotension:

• Midodrine: an alpha-agonist that increases vasomotor and venomotor tone, improving orthostatic blood pressure and ameliorating symptoms of orthostatic hypotension 3
• Fludrocortisone: a mineralocorticoid that is often used as a first-line treatment for orthostatic hypotension, although the quality of evidence is low 4, 5
• Pyridostigmine: an acetylcholinesterase inhibitor that has been shown to improve orthostatic blood pressure and symptoms in patients with neurogenic orthostatic hypotension 6
• Droxidopa: a medication that has been shown to be effective in treating neurogenic orthostatic hypotension, with a strong recommendation level based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) 5

Alternative Agents

In selected cases, the following alternative agents can be considered:

• Yohimbine: an alpha-2 adrenergic antagonist that may be useful in treating orthostatic hypotension, although the quality of evidence is low 5
• Atomoxetine: a norepinephrine reuptake inhibitor that may be useful in treating orthostatic hypotension, although the quality of evidence is low 5
• Fluoxetine: a selective serotonin reuptake inhibitor that may be useful in treating orthostatic hypotension, although the quality of evidence is very low 5
• Ergot alkaloids: a class of medications that may be useful in treating orthostatic hypotension, although the quality of evidence is very low 5
• Ephedrine: a medication that may be useful in treating orthostatic hypotension, although the quality of evidence is very low 5
• Phenylpropanolamine: a medication that may be useful in treating orthostatic hypotension, although the quality of evidence is very low 5
• Octreotide: a medication that may be useful in treating severe postprandial hypotension, with a strong recommendation level based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) 5
• Indomethacin: a nonsteroidal anti-inflammatory medication that may be useful in treating orthostatic hypotension, although the quality of evidence is very low 5
• Ibuprofen: a nonsteroidal anti-inflammatory medication that may be useful in treating orthostatic hypotension, although the quality of evidence is very low 5
• Caffeine: a medication that may be useful in treating orthostatic hypotension, although the quality of evidence is very low 5
• Methylphenidate: a medication that may be useful in treating orthostatic hypotension, although the quality of evidence is very low 5
• Desmopressin: a medication that may be useful in treating orthostatic hypotension, although the quality of evidence is very low 5

Treatment Persistence

The median persistence on treatment with midodrine and fludrocortisone is approximately 254-259 days, with a high rate of treatment discontinuation 7