From the Guidelines
Beta-blockers work for Postural Orthostatic Tachycardia Syndrome (POTS) by blocking the effects of adrenaline on beta-adrenergic receptors in the heart, which reduces heart rate and helps control the excessive tachycardia that occurs when POTS patients stand up. This is supported by the 2022 ACC expert consensus decision pathway, which suggests that low-dose beta-blockers, such as bisoprolol, metoprolol, nebivolol, or propranolol, may be used empirically to slow the heart rate and alleviate symptoms in POTS patients 1.
The mechanism of action of beta-blockers in POTS involves inhibiting the beta-2 adrenergic receptor–mediated vasodilation, which can help to control debilitating symptoms in those with orthostatic intolerance with a hyper-adrenergic state 1. Nonselective beta-blockers, such as propranolol, may be particularly useful in this regard, as they can also help to alleviate symptoms of anxiety and migraine, which are common comorbidities in POTS patients 1.
In terms of specific dosing, the evidence suggests that low-dose beta-blockers can be effective in managing POTS symptoms, with dosages such as propranolol starting at 10-20mg once or twice daily, metoprolol starting at 25-50mg daily, and bisoprolol starting at 2.5-5mg daily 1. However, it is essential to note that beta-blockers may not be suitable for all POTS patients, particularly those with low blood pressure, as they can sometimes lower blood pressure further 1.
Overall, beta-blockers can be a useful adjunctive treatment for POTS, particularly when used in conjunction with other therapies such as increased fluid and salt intake, compression garments, and gradual exercise programs 1. Key points to consider when using beta-blockers for POTS include:
- Starting with low doses and gradually titrating upwards as needed
- Monitoring for potential side effects, such as fatigue, dizziness, and sleep disturbances
- Using beta-blockers in conjunction with other treatments for comprehensive POTS management
- Avoiding beta-blockers in patients with low blood pressure or other contraindications 1.
From the FDA Drug Label
In controlled clinical studies, nadolol at doses of 40 to 320 mg/day has been shown to decrease both standing and supine blood pressure, the effect persisting for approximately 24 hours after dosing The mechanism of the antihypertropic effects of beta-adrenergic receptor blocking agents has not been established; however, factors that may be involved include (1) competitive antagonism of catecholamines at peripheral (non-CNS) adrenergic neuron sites (especially cardiac) leading to decreased cardiac output, (2) a central effect leading to reduced tonic-sympathotic nerve outflow to the periphery, and (3) suppression of renin secretion by blockade of the beta-adrenergic receptors responsible for renin release from the kidneys. Beta-blockers, such as nadolol, work for Postural Orthostatic Tachycardia Syndrome (POTS) by:
- Decreasing heart rate: By blocking the effects of catecholamines on the heart, beta-blockers reduce heart rate and cardiac output.
- Reducing sympathetic nerve outflow: Beta-blockers may also reduce sympathetic nerve activity, which can contribute to the symptoms of POTS. However, the exact mechanism of how beta-blockers work for POTS is not fully established and may involve multiple factors 2.
From the Research
Mechanism of Beta-Blockers in POTS
- Beta-blockers work by blocking the effects of the hormone epinephrine, also known as adrenaline, and by slowing the heart rate and reducing its workload 3, 4.
- In patients with postural orthostatic tachycardia syndrome (POTS), beta-blockers can help to reduce the excessive increase in heart rate that occurs when standing up 3, 5.
- The use of beta-blockers in POTS is particularly effective in patients with a hyperadrenergic phenotype, where there is an excessive production of norepinephrine or impaired reuptake, leading to sympathetic overactivity 6, 4.
Efficacy of Beta-Blockers in POTS
- Studies have shown that beta-blockers, such as propranolol, can significantly reduce symptoms and improve quality of life in patients with POTS 3, 5, 7.
- A systematic review and meta-analysis found that beta-blockers were effective in treating POTS in children and adolescents, alleviating orthostatic intolerance and improving hemodynamic abnormalities 5.
- However, the optimal dose of beta-blockers in POTS is still unclear, with some studies suggesting that low-dose beta-blockers may be more effective than high-dose beta-blockers in improving symptoms 3.
Comparison with Other Treatments
- Beta-blockers have been compared to other treatments, such as exercise training, in the management of POTS 7.
- While beta-blockers can help to reduce symptoms and improve hemodynamics, exercise training has been shown to be superior in restoring upright hemodynamics, normalizing renal-adrenal responsiveness, and improving quality of life in patients with POTS 7.