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β-Adrenoceptor Drugs and Parkinson’s Disease: A Nationwide Nested Case–Control Study

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Abstract

Background

Potential relationships between β-adrenergic drugs and α-synuclein synthesis in Parkinson’s disease (PD) have been recently suggested.

Objective

This study investigated the putative association between β-adrenoceptor drug exposure and PD occurrence.

Methods

A nested case–control study was performed in the Echantillon Généraliste des Bénéficiaires (EGB) (a 1/97th random sample of affiliates to the French Insurance System). Incident PD patients diagnosed between 01/01/2008 and 31/12/2017 (index date) were matched 1:1 to controls by gender, birth year, and insurance scheme. Exposure to any β-agonist and to any β-antagonist was compared between cases and controls within 1–2 years before the index date, and exposure to salbutamol and to propranolol was individualized. The association between PD and β-adrenoceptor drugs was investigated through conditional logistic regression models adjusted for potential confounding factors. Because of a statistical interaction between β-agonists and diabetes, results were stratified according to the presence of diabetes.

Results

Among the 2225 incident PD patients identified in the EGB (mean age 75.6 ± 10.2 years, sex ratio 1.04), no significant association was found between PD and β-antagonists (adjusted odds ratio [aOR] 1.05 [95% confidence interval 0.91–1.20]), except for propranolol (aOR 2.11 [1.38–3.23]). For β-agonists, a protective association in non-diabetic patients (aOR 0.75 [0.60–0.93]) and an opposite and significant association in diabetic patients (aOR 1.61 [1.02–2.55]) were observed. Similar results were found with salbutamol.

Conclusion

This study did not identify an increased risk of PD occurrence after β-antagonist exposure, except for propranolol (potential protopathic bias). The discordant results observed with β-agonists in patients with or without diabetes deserve further exploration of the influence of diabetic comorbidity on PD occurrence and evolution.

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Author information

Authors and Affiliations

  1. Service de Pharmacologie Médicale Et Clinique, Faculté de Médecine, Centre Hospitalier Universitaire, 37 allées Jules-Guesde, Toulouse, France

    Sibylle de Germay, Cécile Conte, Olivier Rascol, Jean-Louis Montastruc & Maryse Lapeyre-Mestre

  2. UMR 1027 INSERM Pharmacoépidémiologie, Université Paul Sabatier Toulouse III, Toulouse, France

    Sibylle de Germay, Cécile Conte, Jean-Louis Montastruc & Maryse Lapeyre-Mestre

  3. Faculté de Médecine, Centre de PharmacoVigilance, Pharmacoépidémiologie Et D’Informations Sur Le Médicament, Centre Hospitalier Universitaire, Toulouse, France

    Jean-Louis Montastruc

  4. CIC INSERM 1436, Paris, France

    Cécile Conte, Olivier Rascol, Jean-Louis Montastruc & Maryse Lapeyre-Mestre

  5. Réseau NS-PARK/FCRIN Et Centre COEN NeuroToul, Toulouse, France

    Olivier Rascol & Jean-Louis Montastruc

Authors
  1. Sibylle de Germay
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  2. Cécile Conte
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  4. Jean-Louis Montastruc
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  5. Maryse Lapeyre-Mestre
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Contributions

SDG, CC, and MLM designed the study. SDG and CC performed the statistical analysis. SDG, CC, MLM, OR, and JLM analyzed the data. SDG and MLM wrote the paper. All authors reviewed the successive versions of the manuscript and approved the final version.

Corresponding author

Correspondence to Sibylle de Germay.

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Funding

The work was performed during the university research time of the authors, without funding agencies.

Conflict of Interest

All authors declare no support from any organization for the submitted work. Sibylle de Germay, Cécile Conte, Jean-Louis Montastruc, and Maryse Lapeyre-Mestre have no conflict of interest. Independently of this work, Olivier Rascol reports scientific grants from Agence Nationale de la Recherche, Centre Hospitalier Universitaire de Toulouse, France-Parkinson, INSERM-DHOS Recherche Clinique Translationnelle, Michael J Fox Foundation, Programme Hospitalier de Recherche Clinique, European Commission (FP7, H2020), and Cure Parkinson IK; Olivier Rascol has acted as scientific advisor for AbbVie, Adamas, Acorda, Addex, AlzProtect, Apopharma, Astrazeneca, Axovant, Bial, Biogen, Britannia, Buckwang, Cerespir, Clevexel, Denali, INC Research, Lundbeck, Lupin, Merck, MundiPharma, Neuratris, Neuroderm, Novartis, ONO Pharma, Osmotica, Parexel, Pfizer, Prexton Therapeutics, Quintiles, Roche, Sanofi, Servier, Sunovion, Théranexus, Takeda, Teva, UCB, Vectura, Watermark Research, XenoPort, XO, and Zambon.

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de Germay, S., Conte, C., Rascol, O. et al. β-Adrenoceptor Drugs and Parkinson’s Disease: A Nationwide Nested Case–Control Study. CNS Drugs 34, 763–772 (2020). https://doi.org/10.1007/s40263-020-00736-2

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