PHARMACOEPIDEMIOLOGY AND PRESCRIPTION Tamoxifen and the risk of Parkinsonism: a case/non-case study François Montastruc 1,2,3,4 & Farzin Khosrow-Khavar 5,6 & Sibylle de Germay 1,2,7 & Christel Renoux 5,6,8 & Vanessa Rousseau 2,3,4,7 & Geneviève Durrieu 2,3 & Marion Montastruc 9 & Olivier Rascol 1,2,4,10 & Agnès Sommet 1,2,4,7,10 & Maryse Lapeyre-Mestre 1,2,4,7,10 & Justine Benevent 1,2,3,7 & Jean-Louis Montastruc 1,2,3,4,7,10 Received: 13 April 2018 /Accepted: 24 May 2018 # Springer-Verlag GmbH Germany, part of Springer Nature 2018 Abstract Background Three studies have suggested a potential positive association between the use of tamoxifen in breast cancer and Parkinsonism, mainly after long-term exposure. Objectives To explore this potential signal, we performed a case/non-case study using the World Health Organization Global Individual Case Safety Reports (ICSRs) database, VigiBase® between 1979 and 2018. Methods Among women ≥ 55 years, we measured the risk of reporting BParkinsonism^ compared with all other adverse drug reactions [as a reporting odds ratio (ROR 95% CI)] for tamoxifen compared to all other drugs or aromatase inhibitors. Results During the study period, 356 ICSRs of Parkinsonism reported with tamoxifen were identified. We failed to find a positive association between tamoxifen exposure and Parkinsonism in comparison with exposure to other drugs (ROR = 0.79; 95% CI 0.71–0.88) or aromatase inhibitors (ROR = 0.39; 95% CI 0.33–0.46). Conclusion This study did not find evidence for Parkinsonism associated with tamoxifen. Keywords Tamoxifen . Parkinsonism . Adverse drug reaction . Pharmacovigilance . Drug safety Introduction Drug-induced Parkinsonism (DIP) is believed to be the second cause of Parkinsonism after idiopathic Parkinson’ s disease (PD) [1–3]. The main drugs that have been associated with Parkinsonism are D2 dopaminergic antagonists, used as anti- psychotics or antiemetics [1–3]. Recently, three studies report- ed an association between tamoxifen, a competitive inhibitor of estradiol binding to the estrogen receptor [4], used to treat breast cancer and risk of PD, mainly after long-term exposure [5–7]. The pharmacodynamic explanation of these findings involves the well-known neuroprotective effects of estrogens on nigrostriatal pathways [8]. In fact, tamoxifen was shown to decrease striatal dopamine concentrations in the model of methamphetamine-induced neurotoxicity in mice [9]. These data led us to investigate this potential association using VigiBase®, the World Health Organization (WHO) Global Individual Case Safety Report (ICSR) database. * Jean-Louis Montastruc jean-louis.montastruc@univ-tlse3.fr 1 Laboratoire de Pharmacologie Médicale et Clinique, Faculté de Médecine, Université de Toulouse, 37 allées Jules-Guesde, 31000 Toulouse, France 2 Service de Pharmacologie Médicale et Clinique, Centre Hospitalier Universitaire de Toulouse, Toulouse, France 3 Centre Régional de PharmacoVigilance, de Pharmacoépidémiologie et d’Informations sur le Médicament, Centre Hospitalier Universitaire de Toulouse, Toulouse, France 4 NeuroToul Centre of Excellence in Neurodegeneration, Centre Hospitalier Universitaire de Toulouse, Toulouse, France 5 Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Québec, Canada 6 Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Québec, Canada 7 INSERM UMR 1027, Faculté de Médecine de Toulouse, Université de Toulouse, Toulouse, France 8 Department of Neurology and Neurosurgery, McGill University, Montreal, Québec, Canada 9 Institut Universitaire du Cancer Toulouse-Oncopôle, 1 avenue Irène-Joliot-Curie, 31059 Toulouse, France 10 CIC INSERM 1436, Centre Hospitalier Universitaire de Toulouse, Université de Toulouse, Toulouse, France European Journal of Clinical Pharmacology https://doi.org/10.1007/s00228-018-2496-3