What is the role of droxidopa in treating Postural Orthostatic Tachycardia Syndrome (POTS)?

From the Guidelines

Droxidopa can be beneficial in treating Postural Orthostatic Tachycardia Syndrome (POTS), particularly in patients with low blood pressure or norepinephrine deficiency, as it improves symptoms of neurogenic orthostatic hypotension due to Parkinson disease, pure autonomic failure, and multiple system atrophy, as noted in the 2017 ACC/AHA/HRS guideline 1. The typical starting dose is 100mg three times daily, which can be gradually increased every 24-48 hours to a maximum of 600mg three times daily based on symptom improvement and tolerability. Droxidopa works by increasing norepinephrine levels, which helps constrict blood vessels and raise blood pressure, thereby reducing orthostatic symptoms like dizziness, lightheadedness, and tachycardia upon standing. Some key points to consider when using droxidopa for POTS include:

• Patients should take their last daily dose at least 3 hours before bedtime to avoid supine hypertension.
• Common side effects include headache, dizziness, nausea, and hypertension.
• Blood pressure monitoring is essential during dose adjustments.
• While droxidopa is FDA-approved for neurogenic orthostatic hypotension, its use in POTS is often off-label, and it's typically considered after lifestyle modifications and first-line medications like midodrine or fludrocortisone have proven insufficient, as mentioned in the 2022 standards of medical care in diabetes 1.
• Patients should continue non-pharmacological measures like adequate hydration, increased salt intake, compression garments, and gradual positional changes even while taking droxidopa, as recommended in the 2021 standards of medical care in diabetes 1. It's also important to note that the therapeutic goal in treating orthostatic hypotension is to minimize postural symptoms rather than to restore normotension, and most patients require both nonpharmacologic measures and pharmacologic measures, as stated in the 2022 standards of medical care in diabetes 1.

From the Research

Role of Droxidopa in Treating POTS

• Droxidopa is an orally administered amino acid that is converted to norepinephrine and thought to improve both blood pressure and symptoms in patients with orthostatic intolerance 2.
• A retrospective study found that droxidopa appears to improve some symptoms of orthostatic intolerance in patients with POTS, but has a diminutive impact on quality of life and blood pressure 2.
• The study reported that symptoms of dizziness, syncope, and fatigue were reduced after treatment with droxidopa, but only 27% of patients reported improved quality of life after treatment 2.
• Another study found that droxidopa is one of the pharmacologic treatment options for POTS that has been studied with a positive impact, but with a low sample size 3.

Limitations and Challenges

• The current literature on pharmacologic treatments for POTS, including droxidopa, is inconsistent and unstandardized 4, 3, 5.
• Most studies on droxidopa and other pharmacologic treatments for POTS have small sample sizes and are underpowered, making it difficult to draw conclusions about their efficacy 3, 5.
• There is a need for further assessment in large clinical trials to evaluate the efficacy of droxidopa and other pharmacologic treatments for POTS 2, 3, 5.

Clinical Considerations

• The diagnosis and treatment of POTS can be complex and require a comprehensive approach, including patient education, non-pharmacologic treatment options, and pharmacologic treatments tailored to the individual patient's needs 4, 6.
• Clinicians should be aware of the potential benefits and limitations of droxidopa and other pharmacologic treatments for POTS, and consider the individual patient's symptoms, medical history, and response to treatment when making treatment decisions 2, 4, 3, 5, 6.