Comprehensive Real-World Assessment of Marketed Medications to Guide Parkinson's Drug Discovery
| Autor: | David M. Kern, M. Soledad Cepeda, Guy R. Seabrook, Simon Lovestone |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male medicine.medical_specialty Databases Factual Adrenergic beta-Antagonists Modafinil 030204 cardiovascular system & hematology Rate ratio 030226 pharmacology & pharmacy Antiparkinson Agents Cohort Studies 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacotherapy Internal medicine Drug Discovery Product Surveillance Postmarketing Medicine Humans Pharmacology (medical) Original Research Article Parkinson Disease Secondary business.industry Methylphenidate Armodafinil Parkinsonism General Medicine medicine.disease Discontinuation chemistry Female business Cohort study medicine.drug |
| Zdroj: | Clinical Drug Investigation |
| ISSN: | 1179-1918 |
| Popis: | Background Parkinson’s disease is a disorder growing in prevalence, disability, and deaths. Healthcare databases provide a ‘real-world’ perspective for millions of individuals. We envisioned helping accelerate drug discovery by using these databases. Objectives The objectives of this study were to assess the association of marketed medications with the risk of parkinsonism in four US claims databases and to evaluate the consistency of the association of β-adrenoreceptor modulation with parkinsonism. Methods The study was conducted using a self-controlled cohort design in which subjects served as their own control. The time from treatment initiation until discontinuation or end of observation was the exposed period and a similar time preceding medication was the unexposed period. Medications were studied at ingredient and class level. The incidence rate ratio (IRR) and combined IRR were calculated. Results We assessed 2181 drugs and 117,015,066 people. Diphenhydramine, isradipine, methylphenidate, armodafinil, and modafinil were associated with reduced risk for parkinsonism in at least two databases. Armodafinil, modafinil, methylphenidate, and the β-agonist albuterol were associated with a 56%, 54%, 39%, and 17% reduction in the risk of having parkinsonism, respectively. Isradipine results were heterogeneous and no significant association was found. Propranolol was associated with a 32% increased risk, the only β-adrenoceptor antagonist (β-blocker) associated with an increased risk. Conclusions Armodafinil, modafinil, and methylphenidate were associated with a decreased risk of parkinsonism, as were β-agonists. Of the β-blockers, only propranolol was associated with increased risk. Healthcare database analyses that incorporate scientific rigor provide insight and direction for drug discovery efforts. These findings show association not causality; however, they offer considerable support to the association between β-adrenergic receptor modulation and risk of Parkinson’s disease. Electronic supplementary material The online version of this article (10.1007/s40261-019-00830-4) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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