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The Role of Atomoxetine for Parkinson Disease–Related Executive Dysfunction

A Systematic Review

Warner, Carly B., PharmD, BCPS*; Ottman, Andreina A., PharmD*; Brown, Jamie N., PharmD, BCPS, BCACP

Journal of Clinical Psychopharmacology: December 2018 - Volume 38 - Issue 6 - p 627–631
doi: 10.1097/JCP.0000000000000963
Review Articles

Background Atomoxetine selectively inhibits the reuptake of norepinephrine. Given the noradrenergic system's role in executive function, pharmacotherapy options that affect norepinephrine are of particular clinical interest in Parkinson disease–related executive dysfunction.

Objective The aim of this study was to assess the efficacy and safety of atomoxetine for Parkinson disease–related executive dysfunction.

Methods MEDLINE (1946 to May 2018) and EMBASE (1947 to May 2018) were queried using the search term combination: Parkinson's disease, Parkinson disease, inhibition, impulse behavior, impulse control disorder, executive function, executive dysfunction, cognition, cognitive dysfunction, cognitive defect, response inhibition, strategic planning, strategy, or verbal fluency and atomoxetine hydrochloride or atomoxetine. Studies analyzed for relevance evaluated clinical outcomes of patients treated with atomoxetine for Parkinson disease–related executive dysfunction. Studies appropriate to the objective were evaluated, including 1 open-label flexible dose trial, 2 placebo-controlled longitudinal trials, and 4 placebo-controlled crossover single-dose trials.

Results In patients with Parkinson disease, treatment with atomoxetine resulted in improvements in several markers of executive dysfunction including impulsivity, risk taking, and global cognition. Study durations ranged from single-dose trials to 10 weeks and used varying doses of atomoxetine. Atomoxetine was well tolerated in most studies with some reports of gastrointestinal adverse effects and insomnia.

Conclusions Based on the reviewed literature, atomoxetine continues to be a therapy of interest for the treatment of executive dysfunction in patients with Parkinson disease. Larger long-term trials are necessary to further define the role of atomoxetine for patients with Parkinson disease–related executive dysfunction.

From the *Geriatric Research, Education, and Clinical Center and

Pharmacy Department, Durham Veterans Affairs Health Care System, Durham, NC.

Received May 8, 2018; accepted after revision September 3, 2018.

Reprints: Carly B. Warner, PharmD, BCPS, Pharmacy Department (119), Durham VA Medical Center, 508 Fulton St, Durham, NC 27705 (e-mail:

Ethical approval for research involving human participants and/or animals was not applicable.

The authors report atomoxetine is not labeled for the use under discussion in this manuscript.

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