Advertisement

Drug Safety

, Volume 41, Issue 7, pp 677–683 | Cite as

Sex Differences in Reported Adverse Drug Reactions of Selective Serotonin Reuptake Inhibitors

  • Corine Ekhart
  • Florence van Hunsel
  • Joep Scholl
  • Sieta de Vries
  • Eugene van Puijenbroek
short communication

Abstract

Introduction

Several studies have investigated sex as a risk factor for the occurrence of adverse drug reactions (ADRs) and found that women are more likely to experience ADRs than men.

Objective

The aim of this explorative study was to investigate whether differences exist in reported ADRs of selective serotonin reuptake inhibitors (SSRIs) for men and women in the database of the Netherlands Pharmacovigilance Centre Lareb.

Methods

A ratio of reports concerning women and men, corrected for the number of users, was calculated for all the ADRs reported on SSRIs.

Results

We found that 16 ADRs were statistically significantly more reported in women than men, and four ADRS were reported more in men than women.

Conclusion

ADRs more reported in women than men when using SSRIs were usually dose-related ADRs or commonly occurring ADRs. Differences in the pharmacokinetics of SSRIs between men and women may explain why these reports of dose-related ADRs when using SSRIs concern women more than men.

Notes

Compliance with Ethical Standards

Funding

No sources of funding were used to assist in the preparation of this study.

Conflict of interest

Corine Ekhart, Florence van Hunsel, Joep Scholl, Sieta de Vries and Eugene van Puijenbroek declare that they have no conflicts of interest.

References

  1. 1.
    Franconi F, Brunelleschi S, Steardo L, Cuomo V. Gender differences in drug responses. Pharmacol Res. 2007;55:81–95.CrossRefPubMedGoogle Scholar
  2. 2.
    Zopf Y, Rabe C, Neubert A, Gassmann KG, Rascher W, Hahn EG, et al. Women encounter ADRs more often than do men. Eur J Clin Pharmacol. 2008;64:999–1004.CrossRefPubMedGoogle Scholar
  3. 3.
    Fattinger K, Roos M, Vergeres P, Holenstein C, Kind B, Masche U, et al. Epidemiology of drug exposure and adverse drug reactions in two swiss departments of internal medicine. Br J Clin Pharmacol. 2000;49:158–67.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Martin RM, Biswas PN, Freemantle SN, Pearce GL, Mann RD. Age and sex distribution of suspected adverse drug reactions to newly marketed drugs in general practice in England: analysis of 48 cohort studies. Br J Clin Pharmacol. 1998;46:505–11.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Rodenburg EM, Stricker BH, Visser LE. Sex-related differences in hospital admissions attributed to adverse drug reactions in the Netherlands. Br J Clin Pharmacol. 2011;71:95–104.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Drici MD, Clement N. Is gender a risk factor for adverse drug reactions? The example of drug-induced long QT syndrome. Drug Saf. 2001;24:575–85.CrossRefPubMedGoogle Scholar
  7. 7.
    Warnock JK, Morris DW. Adverse cutaneous reactions to antidepressants. Am J Clin Dermatol. 2002;3:329–39.CrossRefPubMedGoogle Scholar
  8. 8.
    Vilhelmsson A, Svensson T, Meeuwisse A, Carlsten A. What can we learn from consumer reports on psychiatric adverse drug reactions with antidepressant medication? Experiences from reports to a consumer association. BMC Clin Pharmacol. 2011;11:16.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    D’Incau P, Lapeyre-Mestre M, Carvajal A, Donati M, Salado I, Rodriguez L, et al. No differences between men and women in adverse drug reactions related to psychotropic drugs: a survey from France, Italy and Spain. Fundam Clin Pharmacol. 2014;28:342–8.CrossRefPubMedGoogle Scholar
  10. 10.
    Kostev K, Rex J, Eith T, Heilmaier C. Which adverse effects influence the dropout rate in selective serotonin reuptake inhibitor (SSRI) treatment? Results for 50,824 patients. Ger Med Sci. 2014;12:Doc15.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Brown EG, Wood L, Wood S. The medical dictionary for regulatory activities (MedDRA). Drug Saf. 1999;20:109–17.CrossRefPubMedGoogle Scholar
  12. 12.
    ATC/DDD Index 2018. https://www.whocc.no/atc_ddd_index/. Accessed 30 Jan 2018.
  13. 13.
    Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30:239–45.CrossRefPubMedGoogle Scholar
  14. 14.
    Debonnel G, Saint-Andre E, Hebert C, de Montigny C, Lavoie N, Blier P. Differential physiological effects of a low dose and high doses of venlafaxine in major depression. Int J Neuropsychopharmacol. 2007;10:51–61.CrossRefPubMedGoogle Scholar
  15. 15.
    GIPdatabase - drug information system of the Dutch Health Care Insurance Board. http://www.gipdatabank.nl. Accessed 8 Feb 2017.
  16. 16.
    Preskorn SH. Clinically relevant pharmacology of selective serotonin reuptake inhibitors. An overview with emphasis on pharmacokinetics and effects on oxidative drug metabolism. Clin Pharmacokinet. 1997;32(Suppl 1):1–21.CrossRefPubMedGoogle Scholar
  17. 17.
    Meyboom RH, Lindquist M, Egberts AC. An ABC of drug-related problems. Drug Saf. 2000;22:415–23.CrossRefPubMedGoogle Scholar
  18. 18.
    Bigos KL, Pollock BG, Stankevich BA, Bies RR. Sex differences in the pharmacokinetics and pharmacodynamics of antidepressants: an updated review. Gend Med. 2009;6:522–43.CrossRefPubMedGoogle Scholar
  19. 19.
    Reis M, Lundmark J, Bengtsson F. Therapeutic drug monitoring of racemic citalopram: a 5-year experience in Sweden, 1992–1997. Ther Drug Monit. 2003;25:183–91.CrossRefPubMedGoogle Scholar
  20. 20.
    Reis M, Olsson G, Carlsson B, Lundmark J, Dahl ML, Walinder J, et al. Serum levels of citalopram and its main metabolites in adolescent patients treated in a naturalistic clinical setting. J Clin Psychopharmacol. 2002;22:406–13.CrossRefPubMedGoogle Scholar
  21. 21.
    Ronfeld RA, Tremaine LM, Wilner KD. Pharmacokinetics of sertraline and its N-demethyl metabolite in elderly and young male and female volunteers. Clin Pharmacokinet. 1997;32(Suppl 1):22–30.CrossRefPubMedGoogle Scholar
  22. 22.
    Ferguson JM, Hill H. Pharmacokinetics of fluoxetine in elderly men and women. Gerontology. 2006;52:45–50.CrossRefPubMedGoogle Scholar
  23. 23.
    Gex-Fabry M, Eap CB, Oneda B, Gervasoni N, Aubry JM, Bondolfi G, et al. CYP2D6 and ABCB1 genetic variability: influence on paroxetine plasma level and therapeutic response. Ther Drug Monit. 2008;30:474–82.PubMedGoogle Scholar
  24. 24.
    Geneesmiddeleninformatiebank. Summary of product characteristics. http://www.geneesmiddeleninformatiebank.nl. Accessed 8 Feb 2017.
  25. 25.
    Jakubovski E, Varigonda AL, Freemantle N, Taylor MJ, Bloch MH. Systematic review and meta-analysis: dose-response relationship of selective serotonin reuptake inhibitors in major depressive disorder. Am J Psychiatry. 2016;173:174–83.CrossRefPubMedGoogle Scholar
  26. 26.
    Bech P, Tanghoj P, Andersen HF, Overo K. Citalopram dose-response revisited using an alternative psychometric approach to evaluate clinical effects of four fixed citalopram doses compared to placebo in patients with major depression. Psychopharmacology (Berl). 2002;163:20–5.CrossRefGoogle Scholar
  27. 27.
    Rouve N, Bagheri H, Telmon N, Pathak A, Franchitto N, Schmitt L, et al. Prescribed drugs and violence: a case/noncase study in the French PharmacoVigilance Database. Eur J Clin Pharmacol. 2011;67:1189–98.CrossRefPubMedGoogle Scholar
  28. 28.
    Molero Y, Lichtenstein P, Zetterqvist J, Gumpert CH, Fazel S. Selective serotonin reuptake inhibitors and violent crime: a cohort study. PLoS Med. 2015;12:e1001875.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Inch J, Watson MC, Anakwe-Umeh S. Patient versus healthcare professional spontaneous adverse drug reaction reporting: a systematic review. Drug Saf. 2012;35:807–18.CrossRefPubMedGoogle Scholar
  30. 30.
    Miller MA. Gender-based differences in the toxicity of pharmaceuticals—the Food and Drug Administration’s perspective. Int J Toxicol. 2001;20:149–52.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Netherlands Pharmacovigilance Centre Lareb’s-HertogenboschThe Netherlands
  2. 2.Department of Clinical Pharmacy and PharmacologyUniversity of Groningen, University Medical Centre GroningenGroningenThe Netherlands
  3. 3.Department of Pharmacy: Pharmacotherapy and Pharmaceutical CareUniversity of GroningenGroningenThe Netherlands

Personalised recommendations