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: 5.63). 01/2009; 24(2):277-82. DOI: 10.1002/mds.22307
Source: PubMed

ABSTRACT 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.

Download full-text


Available from: Kevin Biglan, Mar 10, 2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Noradrenergic dysfunction may play a significant role in cognition in Parkinson's disease due to the early degeneration of the locus coeruleus. Converging evidence from patient and animal studies points to the role of noradrenaline in dopaminergically insensitive aspects of the parkinsonian dysexecutive syndrome, yet the direct effects of noradrenergic enhancement have not to date been addressed. Our aim was to directly investigate these, focusing on impulsivity during response inhibition and decision making. To this end, we administered 40 mg atomoxetine, a selective noradrenaline re-uptake inhibitor to 25 patients with Parkinson's disease (12 female /13 male; 64.4 ± 6.9 years old) in a double blind, randomized, placebo controlled design. Patients completed an extensive battery of neuropsychological tests addressing response inhibition, decision-making, attention, planning and verbal short term memory. Atomoxetine improved stopping accuracy on the Stop Signal Task [F(1,19) = 4.51, P = 0.047] and reduced reflection impulsivity [F(1,9) = 7.86, P = 0.02] and risk taking [F(1,9) = 9.2, P = 0.01] in the context of gambling. The drug also conferred effects on performance as a function of its measured blood plasma concentration: it reduced reflection impulsivity during information sampling [adjusted R(2) = 0.23, F(1,16) = 5.83, P = 0.03] and improved problem solving on the One Touch Stockings of Cambridge [adjusted R(2) = 0.29, F(1,17) = 8.34, P = 0.01]. It also enhanced target sensitivity during sustained attention [F(1,9) = 5.33, P = 0.046]. The results of this exploratory study represent the basis of specific predictions in future investigations on the effects of atomoxetine in Parkinson's disease and support the hypothesis that targeting noradrenergic dysfunction may represent a new parallel avenue of therapy in some of the cognitive and behavioural deficits seen in the disorder.
    Brain 06/2014; DOI:10.1093/brain/awu117 · 10.23 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We propose a coding/decoding strategy to approach the channel capacities for binary intersymbol interference (ISI) channels. The proposed codes are serially concatenated codes: inner matched information rate codes and outer irregular low-density parity-check (LDPC) codes. The whole system is iteratively decodable.
    Information Theory, 2002. Proceedings. 2002 IEEE International Symposium on; 02/2002
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Warning signals can induce a paradoxical increase in reaction time (RT) when detecting targets. Top-down inhibitory control intended to prevent undesired responses to non-target stimuli may account for this effect. This hypothesis assumes the existence of a gating mechanism during conditions of uncertainty that locks the initiation of movement before any stimulus is presented and thus increases the RT to any targets that are not preceded by warning cues. However, direct evidence for the involvement of inhibitory mechanisms in the paradoxical warning effect is still lacking. Event-related potentials (ERPs) were analyzed by means of a target detection task according to two experimental protocols: one requiring inhibition (warned and unwarned trials mixed in the same block) and the other not requiring inhibition (warned and unwarned trials separated into different blocks). The probability that warning signals would be introduced in a block (mixed-block design) dramatically increased RT to unwarned targets and evoked target-locked markers of inhibition in these trials (N2 was evoked and P3 was delayed). Cue-locked ERPs also exhibited a strong N2 component whatever the design. The top-down control implemented in the pre-stimulus period to prevent undesired automatic responses to external events inhibits the triggering of movement. Understanding this gating mechanism may provide insight into various neurological or psychiatric disorders affecting movement initiation, such as akinesia or impulsivity that may both be viewed as disorders of higher order inhibitory control.
    Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 04/2009; 120(4):730-7. DOI:10.1016/j.clinph.2009.02.167 · 2.98 Impact Factor