Effects of paroxetine hydrochloride, a selective serotonin reuptake inhibitor, on refractory vasovagal syncope: a randomized, double-blind, placebo-controlled study
Open accessAbstract
Objectives The purpose of the study was to determine whether the well tolerated serotonin reuptake inhibitor paroxetine hydrochloride could prevent vasovagal syncope in patients resistant to or intolerant of previous traditional therapies.Background Serotonergic mechanisms play a major role in the processes leading to neurocardiogenic vasovagal syncope, and serotonin reuptake inhibitors have been reported to be effective in preventing refractory syncope.Methods Sixty-eight consecutive patients (26 men and 42 women, mean age 44.7+/-16.5 years) with recurrent syncope and positive head-up tilt test and in whom standard therapies with beta-adrenergic blocking agents, vagolytic, negative inotropic or mineral corticoid agents were ineffectual or poorly tolerated were referred for study. Patients randomly received either paroxetine at 20 mg once a day or a placebo. A head-up tilt test was then reperformed after one month of treatment, and the clinical effect was noted over a mean follow-up of 25.4+/-7.9 months.Results The response rates (negative tilt test) after one month of treatment were 61.8% versus 38.2% (p < 0.001) in the paroxetine and placebo groups, respectively. During follow-up spontaneous syncope was reported in six patients (17.6%) in the paroxetine group as compared to 18 patients (52.9%) in the placebo group (p < 0.0001). Only one patient (2.9%) asked to be discontinued from the drug for severe side effects.Conclusions Paroxetine was found to significantly improve the symptoms of patients with vasovagal syncope unresponsive to or intolerant of traditional medications and was well tolerated by patients.
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Based on this evidence, there have been several observational studies and three small randomized trials of serotonin transport inhibitors for prevention of vasovagal syncope.
“Based on this evidence, there have been several observational studies and 3 small, randomized trials on serotonin transport inhibitors for the prevention of vasovagal syncope.130–132”
Paroxetine was effective in one placebo-controlled trial, which included highly symptomatic patients from one institution.
“Paroxetine, a selective serotonin reuptake inhibitor, was effective in one placebo-controlled trial, which included highly symptomatic patients from one institution. 281”
From 2018 ESC Guidelines for the diagnosis and management of syncope (2018) · cites this paper as [281]
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Cites
HEAD-UP TILT: A USEFUL TEST FOR INVESTIGATING UNEXPLAINED SYNCOPE
Kenny, R. A., Bayliss, J. M., Ingram, A., & Sutton, R. (1986) · The Lancet · doi:10.1016/s0140-6736(86)91665-x · Cited by 777 · see citing works
Mark, A. L. (1983) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(83)80014-x · Cited by 721 · see citing works
PASSIVE IMMUNITY AGAINST CHILDHOOD CANCER
Lowry, W. S. (1974) · The Lancet · doi:10.1016/s0140-6736(74)90736-3 · Cited by 518 · see citing works
Methodology of head-up tilt testing in patients with unexplained syncope
Fitzpatrick, A. P., THEODORAKIS, G. N., Vardas, P. E., & Sutton, R. (1991) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(91)90714-k · Cited by 428 · see citing works
Sakuma, I., Togashi, H., Yoshioka, M., Saito, H., Yanagida, M., Tamura, M., Kobayashi, T., Yasuda, H., Gross, S. S., & Levi, R. (1992) · Circulation Research · doi:10.1161/01.res.70.3.607 · Cited by 384 · see citing works
LIESHOUT, J. J. V., Wieling, W., Karemaker, J. M., & Eckberg, D. L. (1991) · Clinical Science · doi:10.1042/cs0810575 · Cited by 322 · see citing works
Raviele, A., GASPARINI, G., Pede, F. D., Delise, P., Bonso, A., & Piccolo, E. (1990) · The American Journal of Cardiology · doi:10.1016/0002-9149(90)91321-v · Cited by 266 · see citing works
Raviele, A., Menozzi, C., Brignole, M., Gasparini, G., Alboni, P., Musso, G., Lolli, G., Oddone, D., Dinelli, M., & Mureddu, R. (1995) · The American Journal of Cardiology · doi:10.1016/s0002-9149(99)80079-4 · Cited by 249 · see citing works
Proposed classification for tilt induced vasovagal syncope
Sutton, R. B. (1992) · Medical Entomology and Zoology · Cited by 230 · see citing works
Abboud, F. M. (1993) · New England Journal of Medicine · doi:10.1056/nejm199304153281510 · Cited by 191 · see citing works
Shalev, Y., Gal, R. A., TCHOU, P. J., Anderson, A. J., Avitall, B., Akhtar, M., & Jazayeri, M. R. (1991) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(91)90798-e · Cited by 163 · see citing works
Usefulness of Fluoxetine Hydrochloride for Prevention of Resistant Upright Tilt Induced Syncope
Grubb, B. P., Wolfe, D. A., Samoil, D., Temesy‐Armos, P. N., Hahn, H., & Elliott, L. (1993) · Pacing and Clinical Electrophysiology · doi:10.1111/j.1540-8159.1993.tb01608.x · Cited by 148 · see citing works
Pathophysiological Aspects of Neurocardiogenic Syncope: Current Concepts and New Perspectives
KOSINSKI, D. J., Grubb, B. P., & Temesy‐Armos, P. N. (1995) · Pacing and Clinical Electrophysiology · doi:10.1111/j.1540-8159.1995.tb04666.x · Cited by 140 · see citing works
Grubb, B. P., Samoil, D., KOSINSKI, D. J., Kip, K. T., & Brewster, P. S. (1994) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(94)90308-5 · Cited by 135 · see citing works
Catecholamines in vasovagal fainting
Chosy, J. J., & Graham, D. T. (1965) · Journal of Psychosomatic Research · doi:10.1016/0022-3999(65)90032-2 · Cited by 117 · see citing works
Reproducibility of Head Upright Tilt Table Test Results in Patients with Syncope
Grubb, B. P., Wolfe, D. A., Temesy‐Armos, P. N., Hahn, H., & Elliott, L. (1992) · Pacing and Clinical Electrophysiology · doi:10.1111/j.1540-8159.1992.tb02921.x · Cited by 114 · see citing works
Neural Control Mechanisms and Vasovagal Syncope
Rea, R. F., & Thames, M. D. (1993) · Journal of Cardiovascular Electrophysiology · doi:10.1111/j.1540-8167.1993.tb01246.x · Cited by 93 · see citing works
Adenosine: Potential modulator for vasovagal syncope
Shen, W.-K., Hammill, S. C., Munger, T. M., Stanton, M. S., Packer, D. L., Osborn, M. J., Wood, D. L., Bailey, K. R., Low, P. A., & Gersh, B. J. (1996) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(96)00100-3 · Cited by 90 · see citing works
Kosinski, D. J., & Grubb, B. P. (1994) · Current Opinion in Cardiology · doi:10.1097/00001573-199401000-00007 · Cited by 56 · see citing works
Role of endogenous opioids and catecholamines in vasovagal syncope.
Wallbridge, D., Maclntyre, H. E., Gray, C., Oldroyd, K., Rae, A., & Cobbe, S. (1996) · European Heart Journal · doi:10.1093/oxfordjournals.eurheartj.a014758 · Cited by 33 · see citing works
The use of antiserotonergic agents for the treatment of acute hemorrhagic shock of cats
Elam, R., Bergmann, F., & Feuerstein, G. (1985) · European Journal of Pharmacology · doi:10.1016/0014-2999(85)90070-6 · Cited by 32 · see citing works
Can serial tilt testing be used to evaluate therapy in neurally mediated syncope?
Morillo, C. A., Klein, G. J., & Gersh, B. J. (1996) · The American Journal of Cardiology · doi:10.1016/s0002-9149(97)89348-4 · Cited by 29 · see citing works
A CNS Serotonergic Mechanism in Acute Central Hypovolemia in Conscious Rabbits?
Evans, R. G., Kapoor, V., & Ludbrook, J. (1992) · Journal of Cardiovascular Pharmacology · doi:10.1097/00005344-199206000-00025 · Cited by 29 · see citing works
Increase in plasma beta endorphins precedes vasodepressor syncope.
Wallbridge, D. R., MacIntyre, H. E., GRAY, C. E., et al. (1994) · Heart · doi:10.1136/hrt.71.6.597 · Cited by 29 · see citing works
Increase in plasma beta endorphins precedes vasodepressor syncope.
Wallbridge, D. R., MacIntyre, H. E., GRAY, C. E., et al. (1994) · Heart · doi:10.1136/hrt.71.5.446 · Cited by 16 · see citing works
Flagged first, then by citations
Research works printed but not linked: 5
- [2]2. Mark AL. The Betzold-Jarish reflex revisited: clinical impli- cations of inhibitory reflexes originating in the heart. J Am Coll Cardiol 1983;1:90 -102.
- [10]10. Wallbridge DR, MacIntyre HE, Gray CE, Oldroyd KG, Rae AP, Cobbe SM. Increase in plasma beta-endorphines pre- cedes vasodepressor syncope. Br Heart J 1994;71:446 -8.
- [17]17. Grubb BP, Kosinski D. Preliminary observations on the use of venlafaxine hydrochloride in refractory orthostatic hypoten- sion. J Serotonin Res 1996;6:89 -94.
- [22]22. Kosinski D, Grubb BP, Temesy-Armos P. The use of serotonin reuptake inhibitors in the treatment of neurally mediated cardiovascular disorders. J Serotonin Res 1994;1:85- 90.
- [26]26. Di Girolamo et al. JACC Vol. 33, No. 5, 1999 Paroxetine and Refractory Vasovagal Syncope April 1999:1227-30
Cited by
Sorted by citations
Developed in collaboration with, European Heart Rhythm Association (EHRA), Heart Failure Association (HFA), and Heart Rhythm Society (HRS), societies, E. B. T. F., European Society of Emergency Medicine (EuSEM), European Federation of Internal Medicine (EFIM), European Union Geriatric Medicine Society (EUGMS), American Geriatrics Society (AGS), European Neurological Society (ENS), et al. (2009) · European Heart Journal · doi:10.1093/eurheartj/ehp298 · Cited by 2,040 · see citing works
2018 ESC Guidelines for the diagnosis and management of syncope
Brignole, M., Moya, A., de Lange, F. J., Deharo, J.-C., Elliott, P. M., Fanciulli, A., Fedorowski, A., Furlan, R., Kenny, R. A., Martín, A., et al. (2018) · European Heart Journal · doi:10.1093/eurheartj/ehy037 · Cited by 1,951 · see citing works
Carruthers, B. M., Jain, A. K., De Meirleir, K. L., Peterson, D. L., Klimas, N. G., Lerner, A. M., Bested, A. C., Flor-Henry, P., Joshi, P., Powles, A. C. P., et al. (2003) · Journal of Chronic Fatigue Syndrome · doi:10.1300/j092v11n01_02 · Cited by 1,180 · see citing works
Sheldon, R. S., Grubb, B. P., Olshansky, B., Shen, W.-K., Calkins, H., Brignole, M., Raj, S. R., Krahn, A. D., Morillo, C. A., Stewart, J. M., et al. (2015) · Heart Rhythm · doi:10.1016/j.hrthm.2015.03.029 · Cited by 1,013 · see citing works
2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope
Shen, W.-K., Sheldon, R. S., Benditt, D. G., Cohen, M. I., Forman, D. E., Goldberger, Z. D., Grubb, B. P., Hamdan, M. H., Krahn, A. D., Link, M. S., et al. (2017) · Heart Rhythm · doi:10.1016/j.hrthm.2017.03.004 · Cited by 484 · see citing works
2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope
Shen, W.-K., Sheldon, R. S., Benditt, D. G., Cohen, M. I., Forman, D. E., Goldberger, Z. D., Grubb, B. P., Hamdan, M. H., Krahn, A. D., Link, M. S., et al. (2017) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2017.03.003 · Cited by 327 · see citing works
Ammirati, F., Colivicchi, F., & Santini, M. (2001) · Circulation · doi:10.1161/hc2601.091708 · Cited by 299 · see citing works
Sheldon, R., Connolly, S., Rose, S., Klingenheben, T., Krahn, A., Morillo, C., Talajic, M., Ku, T., Fouad-Tarazi, F., Ritchie, D., et al. (2006) · Circulation · doi:10.1161/circulationaha.105.535161 · Cited by 278 · see citing works
Madrid, A. H., Ortega, J., Rebollo, J. G., Manzano, J. G., Segovia, J. G., Sánchez, A., Peña, G., & Moro, C. (2001) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(00)01155-4 · Cited by 205 · see citing works
Cardiovascular autonomic dysfunction in Ehlers–Danlos syndrome—Hypermobile type
Hakim, A., O'Callaghan, C., De Wandele, I., Stiles, L., Pocinki, A., & Rowe, P. (2017) · American Journal of Medical Genetics Part C: Seminars in Medical Genetics · doi:10.1002/ajmg.c.31543 · Cited by 163 · see citing works
Fenton, A. M., Hammill, S. C., Rea, R. F., Low, P. A., & Shen, W.-K. (2000) · Annals of Internal Medicine · doi:10.7326/0003-4819-133-9-200011070-00014 · Cited by 158 · see citing works
Shen, W.-K., Sheldon, R. S., Benditt, D. G., Cohen, M. I., Forman, D. E., Goldberger, Z. D., Grubb, B. P., Hamdan, M. H., Krahn, A. D., Link, M. S., et al. (2017) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2017.03.002 · Cited by 155 · see citing works
Rowe, P. C., Calkins, H., DeBusk, K., McKenzie, R., Anand, R., Sharma, G., Cuccherini, B. A., Soto, N., Hohman, P., Snader, S., et al. (2001) · JAMA · doi:10.1001/jama.285.1.52 · Cited by 142 · see citing works
Efficacy of tilt training in the treatment of neurally mediated syncope. A randomized study
Foglia-Manzillo, G. (2004) · Europace · doi:10.1016/j.eupc.2004.01.002 · Cited by 127 · see citing works
Theodorakis, G. N., Leftheriotis, D., Livanis, E. G., Flevari, P., Karabela, G., Aggelopoulou, N., & Kremastinos, D. T. (2006) · EP Europace · doi:10.1093/europace/euj041 · Cited by 81 · see citing works
Is home orthostatic self-training effective in preventing neurally mediated syncope?
ON, Y. K., PARK, J., HUH, J., & SOO KIM, J. (2007) · Pacing and Clinical Electrophysiology · doi:10.1111/j.1540-8159.2007.00725.x · Cited by 78 · see citing works
Long-term outcome of patients with vasovagal syncope
Barón-Esquivias, G., Errázquin, F., Pedrote, A., Cayuela, A., Gómez, S., Aguilera, A., Campos, A., Fernández, M., Valle, J. I., Redondo, M., et al. (2004) · American Heart Journal · doi:10.1016/j.ahj.2003.11.022 · Cited by 60 · see citing works
Takata, T. S., Wasmund, S. L., Smith, M. L., Li, J.-M., Joglar, J. A., Banks, K., Kowal, R. C., Page, R. L., & Hamdan, M. H. (2002) · Circulation · doi:10.1161/01.cir.0000029748.94931.96 · Cited by 57 · see citing works
Norepinephrine transporter inhibition prevents tilt-induced pre-syncope
Schroeder, C., Birkenfeld, A. L., Mayer, A. F., Tank, J., Diedrich, A., Luft, F. C., & Jordan, J. (2006) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2006.04.073 · Cited by 45 · see citing works
Are treatments for vasovagal syncope effective? A meta-analysis
Vyas, A., Swaminathan, P. D., Zimmerman, M. B., & Olshansky, B. (2013) · International Journal of Cardiology · doi:10.1016/j.ijcard.2012.04.144 · Cited by 44 · see citing works
Key challenges in the current management of syncope
Sutton, R., Brignole, M., & Benditt, D. G. (2012) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2012.102 · Cited by 33 · see citing works
The relationship between syncope, depression and anti-depressant use in older adults
Bhangu, J. S., King-Kallimanis, B., Cunningham, C., & Kenny, R. A. (2014) · Age and Ageing · doi:10.1093/ageing/afu003 · Cited by 28 · see citing works
Prognosis after tilt training in patients with recurrent vasovagal syncope
Jang, W. J., Yim, H. R., Lee, S. H., Park, S.-J., Kim, J. S., & On, Y. K. (2013) · International Journal of Cardiology · doi:10.1016/j.ijcard.2013.04.125 · Cited by 23 · see citing works
Current management of syncope: Treatment alternatives
Morillo, C. A., & Baranchuk, A. (2004) · Current Treatment Options in Cardiovascular Medicine · doi:10.1007/s11936-004-0021-8 · Cited by 11 · see citing works
- Authors
- Di Girolamo, E., Di Iorio, C., Sabatini, P., Leonzio, L., Barbone, C., & Barsotti, A.
- Affiliations
- Ospedale SS. Annunziata (IT)
- University of Chieti-Pescara (IT)
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 1999-04
- Volume
- 33
- Issue
- 5
- Pages
- 1227-1230
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W1988783107
- Semantic Scholar
- 47abc6838130aa75929f58233de6c2e00780b314
- Cited by
- 322
- References
- 25
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 5 · 2023: 6 · 2022: 5 · 2021: 7 · 2020: 6 · 2019: 8 · 2018: 9 · 2017: 15 · 2016: 8 · 2015: 8 · 2014: 9 · 2013: 11 · 2012: 16
- FWCI
- 20.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Life Sciences › Neuroscience › Neurology › Vestibular and auditory disorders
- Keywords
- paroxetine, selective serotonin reuptake inhibitors, vasovagal syncope, head-up tilt, serotonin, beta-adrenergic blocking agents, drug tolerability
- MeSH terms
- Acute Disease, Adult, Double-Blind Method, Female, Follow-Up Studies, Humans, Male, Middle Aged, Refractory Period, Electrophysiological, Electrocardiography, Ambulatory, Treatment Outcome, Selective Serotonin Reuptake Inhibitors, Paroxetine, Tilt-Table Test, Syncope, Vasovagal, Secondary Prevention
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