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Paroxetine reduced recurrent syncope in patients who were resistant to or intolerant of other drug therapy

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Di Girolamo E, Di Iorio C, Sabatini P, et al. Effects of paroxetine hydrochloride, a selective serotonin reuptake inhibitor, on refractory vasovagal syncope: a randomized, double-blind, placebo-controlled study. J Am Coll Cardiol. 1999 Apr;33:1227-30.


In patients with recurrent vasovagal syncope who are resistant to or intolerant of traditional drug therapy, does paroxetine hydrochloride, a selective serotonin-reuptake inhibitor (SSRI), prevent syncope?


Randomized, double-blind, placebo-controlled trial with mean follow-up of 25 months.


A university hospital in Italy.


68 consecutive patients (mean age 45 y, 62% women) with refractory syncope and a positive nitrate-potentiated tilt-table test result. The cause of the syncope was not known despite intensive testing and was presumed to be vasovagal; all patients had received conventional medications, which were ineffective or not tolerated. Patients with major endog enous depression or panic disorder were excluded. Follow-up was 100%.


34 patients were allocated to oral paroxetine, 20 mg/d, and 34 patients were allocated to placebo.

Main outcome measures

Recurrence and number of spontaneous episodes of syncope, response to tilt-table testing 1 month after the start of therapy, and adverse effects.

Main results

Patients in the paroxetine group had a lower rate of recurrent syncope {P = 0.002}* and a trend toward a lower rate of positive tilt-table test results than did patients in the placebo group {P = 0.08}* (Table). Symptomatic patients in the paroxetine group had a reduced rate of syncope (8.1 episodes/y before the study vs 1.7 episodes/y during the study); symptomatic patients in the placebo group had a stable rate of syncope (7 episodes/y) before and during the study. Adverse events were reported by 3 patients in the paroxetine group (headache, transient sexual dysfunction, nausea, and diarrhea) and 1 patient in the placebo group (headache). Only 1 patient stopped taking paroxetine because of side effects (headache).


Paroxetine reduced the rate of spontaneous syncope in patients with vaso- vagal syncope who were resistant to or intolerant of conventional drug therapy.

Source of funding: Institutional Fund for Clinical Research.

For correspondence: Dr. E. Di Girolamo, Via F. Molino, 35, 66013 Chieti, Italy. E-mail

*P values calculated from data in article.

Abstract and Commentary also published in ACP Journal Club. 1999;131:67.

Paroxetine vs placebo for patients with syncope who were resistant to or intolerant of conventional drug therapy

Outcomes at a mean of 25 mo Paroxetine Placebo RRR (95% CI) NNT (CI)

Recurrent syncope 17.6% 52.9% 67% (30 to 85) 3 (2 to 8)

Positive tilt-table test result 38.2% 61.8% 38% (­0.5 to 63) Not significant

Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.


The absence of randomized placebo-controlled trials to assess the efficacy of drug therapies for vasovagal syncope has made it difficult to make firm recommendations about drug therapy. The study by Di Girolamo and colleagues is the first randomized placebo-controlled trial of an SSRI, paroxetine, in the treatment of recurrent syncope refractory to previous drug therapy. Nonrandomized studies have noted efficacy with other SSRIs, and some data implicate serotonergic mechanisms in the pathogenesis of vasovagal syncope (1). Despite the small number of patients and the problems inherent in the reproducibility of the results of tilt-table testing, the findings of the study are important and strongly support the use of paroxetine in the management of vasovagal syncope.

Clinicians should recognize that the study population consisted of high-risk patients who had frequent episodes of syncope and that previous drug therapies were not well defined or standardized. In general, education concerning symptoms and provocative triggers and reassurance of the diagnosis are important initial steps for many patients presenting with vasovagal syncope. Recurrent events can be treated with conservative measures, such as increased salt intake or drug therapy with b-blockers, fludrocor-tisone, disopyramide, midodrine, and other SSRIs. A recent study suggests that dual-chamber pacing with a rate drop response feature is beneficial in preventing recurrent vasovagal syncope in patients with documented bradycardia on tilt-table testing (2). Pacing is a promising new therapy, but it remains unclear whether cardiac pacing itself prevented syncope in this study. The effects of pacemaker implantation without a placebo group and the rate-drop response feature may have contributed to the results. Careful patient selection is advised.

Michael H. Kim, MD

Kim A. Eagle, MD

University of Michigan Health System

Ann Arbor, Michigan, USA


1. Grubb BP, Karas BJ. The potential role of serotonin in the pathogenesis of neuro-cardiogenic syncope and related autonomic disturbances. J Interv Card Electrophysiol. 1998;2:325-32.

2. Connolly SJ, Sheldon R, Roberts RS, Gent M. The North American vasovagal pacemaker study (VPS). A randomized trial of permanent cardiac pacing for the prevention of vasovagal syncope. J Am Coll Cardiol. 1999;33:16-20.