Short term heart rate variability is preserved in Parkinson's disease under atomoxetine

Repurposed noradrenergic drugs have been proposed to treat neuropsychiatric symptoms in Parkinsons disease and related conditions. While there is evidence that these drugs can be beneficial for cognition in selected patients, questions remain about their cardiovascular effects. Here we tested whether heart rate variability (HRV) is altered in people with Parkinsons disease, following a single-dose challenge with the noradrenaline reuptake inhibitor atomoxetine (40 mg, oral). Consistent with previous work, our cohort of people with idiopathic Parkinsons disease (n=15) had lower HRV than healthy controls (n=22). Decreased HRV in people with Parkinsons disease was associated with reduced integrity of the caudal locus coeruleus, measured using neuromelanin-sensitive ultra-high field 7T magnetic resonance imaging. Following a randomised double-blind placebo-controlled crossover challenge in the Parkinsons disease group, short-term resting HRV was not significantly altered following atomoxetine. Using Bayesian statistical inference, we demonstrated confidence in the preservation of HRV across measures in the time, frequency, and non-linear domains. Our findings are in favour of a safe cardiovascular profile for atomoxetine in Parkinsons disease, further supporting noradrenergic modulation as a viable treatment strategy for neuropsychiatric symptoms in Parkinsons disease and related disorders.