Hemodynamic Profiles and Tolerability of Modafinil in the Treatment of Postural Tachycardia Syndrome: A Randomized, Placebo-Controlled Trial
Open accessAbstract
BACKGROUND: Postural tachycardia syndrome (POTS) is characterized clinically not only by an exaggerated increase in heart rate (HR), but an associated cognitive impairment that disables many patients. Modafinil might be effective in improving the cognitive symptoms, but modafinil may stimulate the sympathetic nervous system and worsen tachycardia in POTS. We tested the hypothesis that modafinil would worsen tachycardia and orthostatic symptoms in POTS. METHODS: Patients with POTS (n = 54) underwent a randomized crossover trial with modafinil 100 mg versus placebo. Heart rate and systolic blood pressure (SBP) were measured seated and standing before modafinil or placebo administration and then hourly for 4 hours. RESULTS: Over 4 hours, standing HR was not significantly different between the modafinil and placebo groups (analysis of variance [ANOVA] Pdrug = 0.328), but seated SBP was significantly higher in the modafinil group (mean [SD], 109 [12] mm Hg vs 104 [10] mm Hg; P = 0.004). Modafinil also significantly increased both the seated SBP (ANOVA Pdrug = 0.004) and the standing SBP (ANOVA Pdrug = 0.041) over time. There was no significant difference between modafinil and placebo over the 4-hour period with regard to POTS symptom burden scores (14 [12] vs 14 [12]; P = 0.962). CONCLUSIONS: Modafinil did not significantly worsen standing HR or acute orthostatic symptoms in patients with POTS compared with the placebo group and improved upright blood pressure. Therefore, modafinil could be tested as a potential treatment for the cognitive impairment in POTS.
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There was no significant difference between modafinil and placebo over the 4 h period with regard to POTS symptom burden scores.
“there was no significant difference between modafinil and placebo over the 4 h period with regard to POTS symptom burden scores (Kpaeyeh et al., 2014”
From Self-reported symptom burden in postural orthostatic tachycardia syndrome (POTS): A narrative review of observational and interventional studies (2023) · cites this paper as Kpaeyeh et al., 2014
A small study evaluating this showed that modafinil did not significantly worsen standing HR or orthostatic symptoms in POTS.
“A small study evaluating this showed that modafinil did not significantly worsen standing HR or orthostatic symptoms in POTS (115).”
From Postural Orthostatic Tachycardia Syndrome (2019) · cites this paper as [115]
Modafinil 100 mg did not significantly increase acute supine or upright heart rate in POTS patients compared to placebo.
“Kpaeyeh et al. (87) demonstrated that modafinil 100 mg did not significantly increase the acute supine or upright heart rate in POTS patients compared to placebo.”
From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [87]
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Freeman, R., Wieling, W., Axelrod, F. B., Benditt, D. G., Benarroch, E., Biaggioni, I., Cheshire, W. P., Chelimsky, T., Cortelli, P., Gibbons, C. H., et al. (2011) · Autonomic Neuroscience · doi:10.1016/j.autneu.2011.02.004 · Cited by 1,243 · see citing works
Self-citationCognitive enhancing effects of modafinil in healthy volunteers
Turner, D. C., Robbins, T. W., Clark, L., Aron, A. R., Dowson, J. H., & Sahakian, B. J. (2003) · Psychopharmacology · doi:10.1007/s00213-002-1250-8 · Cited by 518 · see citing works
Postural tachycardia syndrome (POTS)
LOW, P. A., SANDRONI, P., JOYNER, M., & SHEN, W. (2009) · Journal of Cardiovascular Electrophysiology · doi:10.1111/j.1540-8167.2008.01407.x · Cited by 358 · see citing works
Postural Tachycardia Syndrome (POTS)
Raj, S. R. (2013) · Circulation · doi:10.1161/circulationaha.112.144501 · Cited by 320 · see citing works
Self-citationClinical Pharmacokinetic Profile of Modafinil
Robertson, P., & Hellriegel, E. T. (2003) · Clinical Pharmacokinetics · doi:10.2165/00003088-200342020-00002 · Cited by 258 · see citing works
Effects of volume loading and pressor agents in idiopathic orthostatic tachycardia
Jacob, G., Shannon, J. R., Black, B., Biaggioni, I., Mosqueda-Garcia, R., Robertson, R. M., & Robertson, D. (1997) · Circulation · doi:10.1161/01.cir.96.2.575 · Cited by 206 · see citing works
Self-citationAcetylcholinesterase inhibition improves tachycardia in postural tachycardia syndrome
Raj, S. R., Black, B. K., Biaggioni, I., Harris, P. A., & Robertson, D. (2005) · Circulation · doi:10.1161/circulationaha.104.497594 · Cited by 171 · see citing works
Self-citationPsychiatric profile and attention deficits in postural tachycardia syndrome
Raj, V, Haman, K. L., Raj, S. R., Byrne, D., Blakely, R. D., Biaggioni, I., Robertson, D., & Shelton, R. C. (2009) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.2008.144360 · Cited by 131 · see citing works
Self-citationOcon, A. J., Messer, Z. R., Medow, M. S., & Stewart, J. M. (2011) · Clinical Science · doi:10.1042/cs20110241 · Cited by 102 · see citing works
Modafinil elicits sympathomedullary activation
Taneja, I., Diedrich, A., Black, B. K., Byrne, D. W., Paranjape, S. Y., & Robertson, D. (2005) · Hypertension · doi:10.1161/01.hyp.0000158267.66763.63 · Cited by 68 · see citing works
Reduced stroke volume during exercise in postural tachycardia syndrome
Masuki, S., Eisenach, J. H., Schrage, W. G., Johnson, C. P., Dietz, N. M., Wilkins, B. W., Sandroni, P., Low, P. A., & Joyner, M. J. (2007) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00175.2007 · Cited by 68 · see citing works
A Randomized, Double-Blind, Crossover Trial of Modafinil on Mood
Taneja, I., Haman, K., Shelton, R. C., & Robertson, D. (2007) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e31802eb7ea · Cited by 54 · see citing works
Self-citationOrthostatic intolerance and the headache patient
Mack, K. J., Johnson, J. N., & Rowe, P. C. (2010) · Seminars in Pediatric Neurology · doi:10.1016/j.spen.2010.04.006 · Cited by 47 · see citing works
THE EFFECTS OF A POOR NIGHT SLEEP ON MOOD, COGNITIVE, AUTONOMIC AND ELECTROPHYSIOLOGICAL MEASURES
Barnett, K. J. (2008) · Journal of Integrative Neuroscience · doi:10.1142/s0219635208001903 · Cited by 45 · see citing works
Kanjwal, K., Saeed, B., Karabin, B. L., Kanjwal, Y., & Grubb, B. P. (2010) · American Journal of Therapeutics · doi:10.1097/mjt.0b013e3181da0763 · Cited by 13 · see citing works
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Research works printed but not linked: 1
- [6]Schondorf R Low PA Idiopathic postural orthostatic tachycardia syndrome: an attenuated form of acute pandysautonomia? Neurology 1993 43 132 137 8423877
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Postural Orthostatic Tachycardia Syndrome
Bryarly, M., Phillips, L. T., Fu, Q., Vernino, S., & Levine, B. D. (2019) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.11.059 · Cited by 245 · see citing works
Postural orthostatic tachycardia syndrome: mechanisms and new therapies
Mar, P. L., & Raj, S. R. (2020) · Annual Review of Medicine · doi:10.1146/annurev-med-041818-011630 · Cited by 122 · see citing works
Self-citationPharmacotherapy for postural tachycardia syndrome
Miller, A. J., & Raj, S. R. (2018) · Autonomic Neuroscience · doi:10.1016/j.autneu.2018.04.008 · Cited by 91 · see citing works
Self-citationKnoop, I., Picariello, F., Jenkinson, E., Gall, N., Chisari, C., & Moss-Morris, R. (2023) · Autonomic Neuroscience · doi:10.1016/j.autneu.2022.103052 · Cited by 21 · see citing works
“…no placebo Green et al., 2014 ++++++++ + +++++++ ++++ +++ Proof-of-concept trial Green et al., 2013 ++++++++ + +++++++ ++++ +++ Proof-of-concept trial Kpaeyeh et al., 2014 ++++++++ + +++++++ ++++ +++ Proof-of-concept trial Mar et al., 2014 +++++++ + ++++++ ++++ ++ Proof-of-concept trial Moon et…”
- Authors
- Kpaeyeh, J., Mar, P. L., Raj, V., Black, B. K., Arnold, A. C., Biaggioni, I., Shibao, C. A., Paranjape, S. Y., Dupont, W. D., Robertson, D., & Raj, S. R.
- Affiliations
- University of Calgary (CA)
- Vanderbilt University (US)
- Corresponding author
- Kpaeyeh, John
- Mar, Philip L.
- Black, Bonnie K.
- Arnold, Amy C.
- Biaggioni, Italo
- Shibao, Cyndya A.
- Paranjape, Sachin Y.
- Robertson, David
- Raj, Satish R.
- ORCID
- Venue
- Journal of Clinical Psychopharmacology
- Published
- 2014-12
- Volume
- 34
- Issue
- 6
- Pages
- 738-741
- ISSN
- 0271-0749 (ISSN-L)
- PMC
- PMC4239166
- OpenAlex
- W2410916369
- Cited by
- 29
- References
- 15
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 4 · 2021: 1 · 2020: 3 · 2019: 3 · 2018: 4 · 2017: 3 · 2016: 4 · 2015: 1
- FWCI
- 2.65
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR000445)
- National Heart, Lung, and Blood Institute (P01HL056693, R01HL102387, P01 HL-56693)
- National Institute of Neurological Disorders and Stroke (U54NS065736)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Neurology › Long-Term Effects of COVID-19
- Keywords
- postural orthostatic tachycardia syndrome, modafinil, heart rate, systolic blood pressure, orthostatic symptoms, cognitive impairment, sympathetic activation, drug tolerability
- MeSH terms
- Modafinil, Adult, Benzhydryl Compounds, Female, Heart Rate, Hemodynamics, Humans, Treatment Outcome, Cross-Over Studies, Postural Orthostatic Tachycardia Syndrome, Young Adult
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