Date: Thursday, June 23, 2016
Session Time: 12:00pm-1:30pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: (1) To reassess the behavioral impact of novel noradrenergic (atomoxetine) and serotonergic (citalopram) therapies for impulsivity and (2) to develop predictive models to identify patient responders in the context of Parkinson’s disease.
Background: Selective noradrenaline (atomoxetine) and serotonin (citalopram) reuptake inhibitors have shown to improve response inhibition in patients with Parkinson’s disease. Both drugs can enhance the neural systems for inhibitory control, partially restoring behavioral performance (stopping efficiency), frontal cortical activity, and/or frontostriatal functional connectivity. However, the behavioral impact of the drugs varied across patients.
Methods: We conducted a double-blind randomized three-way crossover design to investigate the effects of atomoxetine (40mg) and citalopram (30mg) versus placebo in 34 patients with idiopathic Parkinson’s disease. Changes of stopping efficiency and frontal and striatal brain activity were measured with functional MRI. Frontostriatal connectivity was measured with diffusion MRI. Clinical measures include disease severity (UPDRS-III motor subscale), levodopa equivalent dose and cognitive status (MMSE). With the clinical and neuroimaging measures, we built binary classifiers with leave-one-out cross-validation to predict patients’ responses in terms of improved stopping efficiency.
Results: We confirmed that atomoxetine and citalopram can improve response inhibition at both behavioral and brain activity levels. We identified two optimal models: (1) a “clinical” model that predicted individual patients’ responses with 77-79% accuracy for atomoxetine and citalopram, using age, cognitive status and levodopa equivalent dose, and a simple diffusion MRI scan; (2) a “mechanistic” model that explained the behavioral response with 85% accuracy for each drug, using drug-induced changes of brain activations in the striatum and presupplementary motor area from functional MRI.
Conclusions: Our data support growing evidence for the role of noradrenaline and serotonin in inhibitory control and impulsivity. More importantly, the results suggest that individual patients’ response to noradrenergic and serotonergic drugs can be predicted using clinical and neuroimaging measures.
To cite this abstract in AMA style:J.B. Rowe, C. Rae, C. Nombela, T. Ham, P. Vazquez, I. Coyle-Gilchrist, C.R. Housden, B.J. Sahakian, T.W. Robbins, Z. Yes. Predicting therapeutic effects of atomoxetine and citalopram on response inhibition in Parkinson’s disease [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/predicting-therapeutic-effects-of-atomoxetine-and-citalopram-on-response-inhibition-in-parkinsons-disease/. Accessed September 23, 2023.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/predicting-therapeutic-effects-of-atomoxetine-and-citalopram-on-response-inhibition-in-parkinsons-disease/