Atomoxetine for the Treatment of Executive Dysfunction in Parkinson's Disease: A Pilot Open-Label Study

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Movement Disorders (Impact Factor: 5.68). 01/2009; 24(2):277-82. DOI: 10.1002/mds.22307
Source: PubMed


Executive dysfunction (ED) is a prominent and often disabling feature of cognitive impairment in Parkinson's disease (PD). Few studies have examined treatments. Given the role of noradrenergic pathology in ED, atomoxetine, a norepinephrine reuptake inhibitor indicated for attention deficit hyperactivity disorder (ADHD), may be a potential treatment for PD-related ED. Twelve patients with PD and disabling ED completed an 8-week pilot open-label, flexible dose (25-100 mg/day) trial of atomoxetine. On primary outcome measures, atomoxetine was associated with improved ED based on the Clinical Global Impression-Change Scale (75% positive response rate; 95% CI: 43-95%, P < 05) and behavioral measures of ED [Frontal Systems Behavior Scale (FrSBE) Executive Dysfunction and Connors Adult ADHD Rating Scale (CAARS) inattention/memory subscales]. Adverse effects included sleep and gastrointestinal disturbances and hypomania. Atomoxetine is tolerable in PD and may benefit clinical manifestations of ED, warranting further study in controlled trials.

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Available from: Kevin Biglan, Mar 10, 2014
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    • "Verbal memory declines have been documented with both natural (Epperson et al. 2013) and surgical menopause (Sherwin 2005) and may be particularly amenable to improvement if addressed early in the menopause transition. Similarly, a previous study (Epperson et al. 2011) demonstrated that atomoxetine, a non-stimulant medication FDA-approved for the treatment of ADHD (Asherson et al. 2014) and studied with variable success in other disorders (Beglinger et al. 2009; Marsh et al. 2009; Stahl 2003), significantly improved subjective EFs and performance on the verbal paired associates memory task in a similar sample of menopausal women. "
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    • "The randomization groups were matched for age, IQ, education level, disease severity as indexed by the Unified Parkinson's Disease Rating Scale motor subscale (Fahn et al., 1987), total levodopa equivalent daily dose as well as dopamine agonist levodopa equivalent daily dose (Table 1). A dose of 40 mg was used to ensure tolerability based on previous studies (Jankovic, 2009; Marsh et al., 2009; Weintraub et al., 2010b). As peak plasma concentration for atomoxetine is achieved "
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    • "Hence, our findings add further support to the notion that executive deficits in higher order control of actions like internal movement selection and choice processes in Parkinson's disease may be related to neurotransmitter system dysfunction beyond the dopaminergic system, such as, e.g. acetylcholine, noradrenaline or serotonin (Marsh et al., 2009; Schmitt et al., 2010; Narayanan et al., 2013; Ye et al., 2014a, b). "

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