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Acetylcholinesterase Inhibition Improves Tachycardia in Postural Tachycardia Syndrome
Open accessAbstract
Background— Postural tachycardia syndrome (POTS) induces disabling chronic orthostatic intolerance notable for an excessive increase in heart rate that occurs on standing. Many current therapeutic strategies focus on sympatholysis, but the alternative strategy of enhancing cardiovagal tone has not been studied. The objective of this study was to test the hypothesis that acetylcholinesterase inhibitors will attenuate the tachycardia and improve symptom burden in patients with POTS. Methods and Results— Seventeen patients with POTS underwent acute drug trials of pyridostigmine 30 mg orally and placebo, on separate mornings, in a randomized crossover design. Blood pressures, heart rate, and symptoms were assessed while patients were seated and after they had been standing for up to 10 minutes both before the study drug was given and at 2 and 4 hours after study drug. The heart rate was significantly lower at 2 hours after pyridostigmine than after placebo (100±16 versus 111±14 bpm, P =0.001). Pyridostigmine significantly decreased the standing heart rate from baseline (119±16 bpm) at 2 hours (104±16 bpm, P <0.001) and 4 hours (100±16 bpm, P <0.001) after administration. There was no significant change in blood pressure. The decrease in symptom burden within 4 hours after study drug was significantly greater with pyridostigmine than placebo (−10.4±14.0 AU versus 0.6±7.5 AU, P <0.025). Conclusions— Acute acetylcholinesterase inhibition significantly attenuated tachycardia in POTS. There was also an improvement in symptom burden with this promising therapy.
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“The drug blunts orthostatic tachycardia and can improve chronic symptoms but is limited by adverse effects such as diarrhea, abdominal pain and cramps, nausea, and increased urinary urgency and frequency.45,46”
From 2015 Heart Rhythm Society Expert Consensus Statement on the Diagnosis and Treatment of Postural Tachycardia Syndrome, Inappropriate Sinus Tachycardia, and Vasovagal Syncope (2015) · cites this paper as [45]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“A 2005 study found that pyridostigmine (30–60 mg, given orally 3 times daily) can acutely decrease upright heart rate in patients with POTS;48”
From Diagnosis and management of postural orthostatic tachycardia syndrome (2022) · cites this paper as [48]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Three of these experimental proof-of-concept trials, of Desmopressin, Pyridostigmine, and Propranolol (low dose more than high dose and high dose more than placebo) were effective in reducing symptom burden compared to placebo or high dose controls after 4 h tilt test.”
From Self-reported symptom burden in postural orthostatic tachycardia syndrome (POTS): A narrative review of observational and interventional studies (2023) · cites this paper as Raj et al., 2005
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In the citing paper
“This symptom score has been previously used by our center 6 and the symptoms were chosen as they reflect common complaints of patients with POTS.”
From Propranolol Decreases Tachycardia and Improves Symptoms in the Postural Tachycardia Syndrome: Less Is More (2009) · cites this paper as [6]
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“Many patients with POTS have increased sympathetic nervous system tone measured with direct nerve recordings 5 or biochemically with an elevated plasma norepinephrine on standing 6–8.”
From Propranolol Decreases Tachycardia and Improves Symptoms in the Postural Tachycardia Syndrome: Less Is More (2009) · cites this paper as [6]
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“Pyridostigmine (a cholinergic agonist that works by inhibiting acetylcholinesterase) 30 to 60 mg 3 times a day can increase parasympathetic autonomic tone (107,108) and has a lower risk of hypertension compared with other medications.”
From Postural Orthostatic Tachycardia Syndrome (2019) · cites this paper as [107]
In the citing paper
“Increasing parasympathetic tone with pyridostigmine can also curtail HR in POTS [65] (HRS Class IIb) [8].”
From Postural tachycardia syndrome: beyond orthostatic intolerance (2015) · cites this paper as [65]
In the citing paper
“Supine and upright blood pressures were no different between the group that received pyridostigmine and the placebo group.”
From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [80]
In the citing paper
“In a study of 17 POTS patients, symptoms and standing heart rate were significantly reduced after pyridostigmine administration versus placebo in the acute setting (80).”
From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [80]
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“Acetylcholinesterase inhibitor.”
From Postural orthostatic tachycardia syndrome: clinical presentation, aetiology and management (2019) · cites this paper as [99]
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“, 2014), increasing parasympathetic nervous system activity (and therefore decreasing HR) and enhancing cardiovagal tone (Pyridostigmine) (Raj et al., 2005; Moon et al., 2018), increasing blood volume/pressure Table 5c Orthostatic Baseline scores.”
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Postural Orthostatic Tachycardia Syndrome (POTS)
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Moon, J., Lee, H. S., Byun, J.-I., Sunwoo, J.-S., Shin, J.-W., Lim, J.-A., Kim, T.-J., Shin, Y.-W., Lee, K.-J., Jeon, D., et al. (2016) · Journal of the American Society of Hypertension · doi:10.1016/j.jash.2016.01.011 · Cited by 17
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Postural Tachycardia Syndrome (POTS)
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Metadata
- Authors
- Raj, S. R., Black, B. K., Biaggioni, I., Harris, P. A., & Robertson, D.
- Affiliations
- Vanderbilt University (US)
- Venue
- Circulation
- Published
- 2005-05-31
- Volume
- 111
- Issue
- 21
- Pages
- 2734-2740
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2119590578
- Semantic Scholar
- ea9f143f5988a05a320e77ea7e1b2ae553870d10
- Cited by
- 171
- References
- 25
- Citations by year
- 2026: 11 · 2025: 11 · 2024: 12 · 2023: 6 · 2022: 10 · 2021: 8 · 2020: 7 · 2019: 8 · 2018: 9 · 2017: 7 · 2016: 8 · 2015: 6 · 2014: 11 · 2013: 13 · 2012: 10
- FWCI
- 6.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Vanderbilt University (M01 RR00095)
- Deutsches Krebsforschungszentrum
- National Institutes of Health
- National Heart, Lung, and Blood Institute (2P01-HL-56693, P01HL056693)
- National Center for Research Resources (M01RR000095, M01-RR-00095, K23RR020783)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Syncope and Autonomic Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Keywords
- postural orthostatic tachycardia syndrome, acetylcholinesterase inhibitors, pyridostigmine, orthostatic intolerance, heart rate, symptom burden, drug trials
- MeSH terms
- Adult, Blood Pressure, Cholinesterase Inhibitors, Female, Heart Rate, Humans, Male, Middle Aged, Posture, Pyridostigmine Bromide, Tachycardia, Cross-Over Studies
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