Association between selective serotonin-reuptake inhibitor therapy and heart valve regurgitation

https://doi.org/10.1016/S0002-9149(01)01435-7Get rights and content

Abstract

The identification of an association between fenfluramines and valvular disease has raised the possibility of a similar association between another class of medications that increases local levels of serotonin, the selective serotonin-reuptake inhibitors (SSRIs). The objective of this study was to examine the association between heart valve regurgitation and treatment with SSRIs. We examined 5,437 consecutive patients who underwent echocardiography. Patients with a similar likelihood of SSRI treatment were identified by propensity models. The prevalence of regurgitation according to treatment was compared after adjusting for clinical characteristics associated with regurgitation. We also blindly reinterpreted a subset of 2,000 echocardiograms to identify characteristics associated with fenfluramine-associated valvular heart disease such as posterior mitral leaflet restriction. Among 5,437 consecutively hospitalized patients, we identified 292 who had taken SSRIs before admission. Patients taking SSRIs tended to be younger, female, Caucasian, unmarried, and more likely to have psychiatric illness and hypertension (p ≤0.05). The overall prevalence of regurgitation meeting Food and Drug Administration criteria (at least moderate mitral regurgitation or mild aortic regurgitation) was 30%, with no significant difference in prevalence between those receiving SSRIs (26.7%) and controls (30.4%) (p = 0.19). The association remained negative when comparing SSRI-treated patients to controls with similar characteristics. Furthermore, the prevalence of features described in conjunction with fenfluramine exposure, such as posterior mitral leaflet restriction, was not higher in SSRI-treated patients. Among a large consecutive cohort of patients, the prevalence of mitral and aortic regurgitation in patients taking SSRIs was not different from that of controls, suggesting that SSRIs are not associated with valvular disease.

Section snippets

Patient population

We identified consecutive patients hospitalized at Duke University Medical Center between July 1995 and June 1997 who underwent transthoracic echocardiography as part of routine clinical care. Patients with previous valve surgery were excluded. Hospital charts corresponding to the date of echocardiography were reviewed by trained reviewers (physicians and registered nurses) who were blinded to the study question. Demographic and social data, cardiac disease (valvular heart disease, coronary

Demographic and clinical information

Demographic and clinical characteristics for the study population according to SSRI use are listed in Table 1. Of the 5,437 patients, 292 had been treated with SSRI therapy before admission, and an additional 51 patients received SSRIs only during hospitalization. Patients taking SSRIs were more likely to be younger, women, Caucasian, single, and require assistance with activities of daily living (p <0.05). With regard to clinical characteristics, those taking SSRIs were more likely to have

Discussion

In this study of >5,000 patients who underwent echocardiography over a 2-year period, we could not identify any association between SSRI therapy and valvular heart disease. SSRI-treated patients had neither an increased prevalence of valve regurgitation, nor the characteristic valve pathology of posterior mitral leaflet restriction identified with fenfluramine valvular disease. This study has important implications for the large number of patients being treated with SSRIs. These agents are

Acknowledgements

We wish to acknowledge outstanding assistance from C. Mae White of Duke Hospital in procuring medical records and from Tracey Dryden, MA, in editorial support.

References (20)

  • S.E Kimmel et al.

    Detailed examination of fenfluramine-phenteramine users with valve abnormalities identified in Fargo, North Dakota

    Am J Cardiol

    (1999)
  • G.J Perry et al.

    Evaluation of aortic insufficiency by Doppler color flow mapping

    J Am Coll Cardiol

    (1987)
  • J Zoeller

    Top 200 drugsaggressive detailing and direct-to-consumer advertising are landing new products in the top 200 rankings much sooner

    Am Drug

    (1999)
  • H.M Connolly et al.

    Valvular heart disease associated with fenfluramine-phentermine

    N Engl J Med

    (1997)
  • [anonymous] Cardiac valvulopathy associated with exposure to fenfluramine or dexfenfluramine: U.S. Department of Health...
  • H Jick et al.

    A population-based study of appetite-suppressant drugs and the risk of cardiac-valve regurgitation

    N Engl J Med

    (1998)
  • M.A Khan et al.

    The prevalence of cardiac valvular insufficiency assessed by transthoracic echocardiography in obese patients treated with appetite-suppressant drugs

    N Engl J Med

    (1998)
  • N.J Weissman et al.

    An assessment of heart-valve abnormalities in obese patients taking dexfenfluramine, sustained-release dexfenfluramine, or placebo

    N Engl J Med

    (1998)
  • A.J Wood et al.

    Making medicines safer, the need for a drug safety board

    N Engl J Med

    (1998)
  • J.G Jollis et al.

    Fenfluramine and phentermine and cardiovascular findingsthe effect of treatment duration on prevalence of valve abnormalities

    Circulation

    (2000)
There are more references available in the full text version of this article.

Cited by (24)

  • Impact of selective serotonin reuptake inhibitor therapy on heart valves in patients exposed to benfluorex: A multicentre study

    2013, Archives of Cardiovascular Diseases
    Citation Excerpt :

    These data raised a concern about the safety of SSRIs, currently used as first-line therapy in affective disorders with clinically proven efficacy, as these drugs also interfere with serotonin metabolism. Indeed, about one quarter of patients exposed to fenfluramine had been exposed to SSRIs in some reports [16], although the prevalence of SSRI use was lower (12%) in the present study. As fenfluramine increases synaptic levels of 5-HT, fenfluramine has been suspected to induce VHD via a serotonergic mechanism, as previous studies have reported that fenfluramine derivatives have a high affinity for the 5-HT2B receptor, and are full agonists at the 5-HT2B site [26].

  • Fenfluramine disrupts the mitral valve interstitial cell response to serotonin

    2009, American Journal of Pathology
    Citation Excerpt :

    The present study provides novel insights concerning 5HT-related heart valve disease, and also reveals that prior conclusions concerning Fen may have been incomplete in their scope. Furthermore, 5HTT inhibitors, especially the selective 5HT reuptake inhibitors, such as fluoxetine, are widely used for treating depression, and their role over time concerning their potential effects on heart valve disease, either de novo or pre-existing, has been investigated to a very limited extent in a single cross-sectional study.38 In addition, a 5HTT polymorphism in the promoter region of human 5HTT has a Mendelian distribution in the general population.39,40

  • Role of Serotoninergic Pathways in Drug-Induced Valvular Heart Disease and Diagnostic Features by Echocardiography

    2009, Journal of the American Society of Echocardiography
    Citation Excerpt :

    Because serotonin release and serotonin reuptake inhibitors are involved in heart valve disease, concerns have been raised regarding the use of selective serotonin reuptake inhibitors (SSRI) such as fluoxetine, sertraline, paroxetine, and similar drugs used for the treatment of depression as potentially causing heart valve disease. One study examined the association between valvular regurgitation and treatment with SSRIs in 292 patients and compared these with 5145 consecutively hospitalized patients as controls.44 The unadjusted prevalence of left-sided and/or overall heart valve regurgitation was slightly less common among SSRI-treated patients than controls, thus arguing for a lack of an association between SSRIs and heart valve disease.

  • A review of the application of propensity score methods yielded increasing use, advantages in specific settings, but not substantially different estimates compared with conventional multivariable methods

    2006, Journal of Clinical Epidemiology
    Citation Excerpt :

    We excluded 48 articles that did not include analysis of data (28), randomized clinical trials (9), case-control studies (2), and articles primarily analyzing cost-effectiveness (6) or practice patterns (3). Our search revealed 58 substantive medical research studies that used PS in 2003 [18–75], 38 in 2002 [76–113], 28 in 2001 [114–141], 6 in 2000 [142–147], 5 in 1999 [148–152], 5 in 1998 [153–157], and a total of 5 before 1998 [158–162]. Additional articles found through a citation search of the significant methods articles written about PS, using Science Citation Index, yielded 13 medical research studies that used PS in 2003 [163–175], 13 in 2002 [176–188], 11 in 2001 [189–199], 3 in 2000 [200–202], 1 in 1999 [203], 3 in 1998 [204–206], and a total of 3 before 1998 [207–209].

  • Antidepressants and Valvular Heart Disease

    2016, Medicine (United States)
View all citing articles on Scopus

This study was supported by grants from Pfizer, New York, New York; SmithKline Beecham, Collegeville, Pennsylvania, and Eli Lilly, Indianapolis, Indiana; and Patient Oriented Mid-Career Investigator Award K24 HL03995-01 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland. Manuscript received July 17, 2000; revised manuscript received and accepted October 30, 2000.

View full text