Benjamin Pierson ^1* Kyle Apilado ² Marc Alaric Franzos ³ Rhonda Allard ¹ James Mancuso ¹ David Saunders ³ David Tribble ¹ Tracey Koehlmoos ¹

• ¹ Uniformed Services University of the Health Sciences, Bethesda, United States
• ² Henry M Jackson Foundation for the Advancement of Military Medicine (HJF), Bethesda, Maryland, United States
• ³ Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Illinois, United States

Postural Orthostatic Tachycardia Syndrome (POTS) is a complex form of dysautonomia that presents with abnormal autonomic reflexes upon standing, leading to symptoms such as lightheadedness, tachycardia, fatigue and cognitive impairment The COVID-19 pandemic has brought renewed attention to POTS due to its overlap with post-acute sequelae of COVID-19 (PASC). Studies have found that a substantial percentage of COVID-19 survivors exhibit symptoms resembling POTS, elevating POTS diagnoses to previously unseen levels. We systematically reviewed the literature for existing high-quality evidence on potential interventions.A systematic review of the literature was performed to identify studies of oral medications for the management of POTS. We searched for published manuscripts on the medical management of POTS through 6 April 2024 which met prespecified inclusion criteria.We conducted quality appraisal and assessed risk of bias before extracting the data and performing synthesis to determine the current state of the evidence; particularly in the context of PASC.The study search and selection process identified 32 studies that met inclusion criteria, comprising randomized controlled trials, observational studies, and systematic reviews. Most included studies were judged to be of moderate to high quality, with largely low risk of bias. The most frequently studied medications were beta-blockers, ivabradine, and midodrine. Ivabradine and midodrine demonstrated the highest rate of symptomatic improvement, while beta-blockers showed the largest reduction in heart rate variability. Limited evidence was available for PASCassociated POTS, but findings suggest that treatments may have similar efficacy in both PASC and non-PASC cases.Ivabradine, midodrine, and beta-blockers currently appear to be reasonable front-line choices in pharmacologic management of POTS (PASC associated and otherwise). Further RCTs that evaluate long term outcomes of medications are needed to further establish evidence based pharmacologic treatment approaches for POTS. Particular areas of inquiry include differential efficacy of recommended therapies based on POTS subtypes, and a need for treatments directly targeting the underlying autonomic nervous system dysfunction.