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Dopaminergic stimulants and risk of Parkinson's disease

By Michael Wainberg, Dipender Gill, Bowen Su, Mike A Nalls, Robert R Graham, Sudeshna Das, Ioanna Tzoulaki, Nasa Sinnott-Armstrong, Manuel A. Rivas

Posted 11 May 2020
medRxiv DOI: 10.1101/2020.05.06.20089748

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.

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