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

Repurposed noradrenergic drugs have been proposed to treat neuropsychiatric symptoms in Parkinson's 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 Parkinson's 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 Parkinson's disease (n = 15) had lower HRV than healthy controls (n = 22). Select markers of decreased HRV in people with Parkinson's disease were associated with reduced integrity of the caudal locus coeruleus, measured using neuromelanin-sensitive ultra-high-field 7T magnetic resonance imaging. Following a randomized double-blind placebo-controlled crossover challenge in the Parkinson's 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 Parkinson's disease, further supporting noradrenergic modulation as a viable treatment strategy for neuropsychiatric symptoms in Parkinson's disease and related disorders.