Dopaminergic stimulants and risk of Parkinson's disease
Mike A Nalls,
Robert R Graham,
Manuel A. Rivas
Posted 11 May 2020
medRxiv DOI: 10.1101/2020.05.06.20089748
Posted 11 May 2020
Parkinson's disease is characterized by dopaminergic neurodegeneration in the substantia nigra. Although dopaminergic drugs are the mainstay of Parkinson's treatment, their putative disease-modifying properties remain controversial. We explored whether prescription of dopaminergic stimulants for attention-deficit hyperactivity disorder (ADHD) might affect Parkinson's incidence. We performed Cox survival analyses for outpatient Parkinson's diagnosis among ADHD-diagnosed seniors in the Optum Clinformatics Data Mart de-identified administrative claims database, correcting for diverse demographic and socio-economic status covariates. We compared 5,683 sustained users ([≥] 90 days) of dopaminergic stimulants to 252 sustained users of atomoxetine, a noradrenergic first-line ADHD medication. Parkinson's incidence was reduced among sustained dopaminergic stimulant users compared to atomoxetine users (adjusted hazard ratio [HR] 0.15, 95% confidence interval [CI] 0.04-0.56, p = 0.005). Effect sizes were comparable between derivatives of amphetamine (adjusted HR 0.12, 95% CI 0.03-0.48, p = 0.003) and methylphenidate (adjusted HR 0.27, 95% CI 0.04-1.76, p = 0.2). In sensitivity analyses, similar trends were observed when other psychotropics (SSRIs, gabapentin) were used as comparators instead of atomoxetine, or when the threshold for sustained use was defined as 45, 180 or 360 days instead of 90. Thus, sustained dopaminergic stimulant use was associated with lower Parkinson's incidence among seniors with ADHD. Our results are consistent with a protective effect of dopaminergic stimulants on the development of Parkinson's, and support a re-examination of certain dopaminergics, particularly rasagiline and other selective monoamine oxidase B inhibitors, as potential disease-modifying agents.
- Downloaded 1,392 times
- Download rankings, all-time:
- Site-wide: 16,291
- In pharmacology and therapeutics: 29
- Year to date:
- Site-wide: 6,924
- Since beginning of last month:
- Site-wide: 5,799
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!