Voon V, Fernagut PO, Wickens J, Baunez C, Rodriguez M, Pavon N et al. Chronic dopaminergic stimulation in Parkinson's disease: from dyskinesias to impulse control disorders. Lancet Neurology 8: 1140-1149

Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, London, UK.
The Lancet Neurology (Impact Factor: 21.9). 12/2009; 8(12):1140-9. DOI: 10.1016/S1474-4422(09)70287-X
Source: PubMed


Dopamine is an essential neurotransmitter for many brain functions, and its dysfunction has been implicated in both neurological and psychiatric disorders. Parkinson's disease is an archetypal disorder of dopamine dysfunction characterised by motor, cognitive, behavioural, and autonomic symptoms. While effective for motor symptoms, dopamine replacement therapy is associated not only with motor side-effects, such as levodopa-induced dyskinesia, but also behavioural side-effects such as impulse control disorders (eg, pathological gambling and shopping, binge eating, and hypersexuality), punding (ie, abnormal repetitive non-goal oriented behaviours), and compulsive medication use. We review clinical features, overlapping molecular mechanisms, and a specific cognitive mechanism of habit learning that might underlie these behaviours. We integrate these mechanisms with the emerging view of the basal ganglia as a distributive system involved in the selection and facilitation of movements, acts, and emotions.

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Available from: Pierre-Olivier Fernagut
    • "In many cases, pharmacological therapy is unable to provide satisfactory symptom control as the disease progresses and patients on long term medication may develop disabling side effects [1]. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an evidence based treatment in advanced stages of PD as it has been shown to improve motor fluctuations, dyskinesia and quality of life better than medication [2]. Furthermore STN-DBS allows for a reduction in medication [3] which is particularly important for patients suffering from side effects of medication such as impulse control disorders or psychosis. "
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    ABSTRACT: Deep brain stimulation of subthalamic nucleus (STN-DBS) for Parkinson's disease allows for a reduction in medication dosage. Changes in total levodopa equivalent daily dose (LEDD) have been frequently reported, there is little information about changes within the drug classes. We retrospectively assessed the changes in antiparkinsonian drugs dosages in 150 patients from one center who had preoperative and postoperative evaluations at 6 months and 3 years. Two long term subgroups with postoperative follow-up till the 5th-6th year (n = 58) and 10th year (n = 15) were included. The major modifications in medication dosage occurred during the initial postoperative period. LEDD was reduced by 53.4% compared to baseline at 6 months and 47.9% at 3 years. Fifty six percent and 41.3% of the patients were on monotherapy, 9.3% on no medication at 6 months and 6.7% at 3 years post surgery. Patients on levodopa, or dopamine agonists showed similar reductions. At the 3rd year the oldest group of patients showed a significant decrease in dopamine agonists. The number of patients treated with amantadine was significantly reduced; however the number of patients treated with antidepressants was significantly increased over the first 3 years. Annual medication costs per patient were decreased after the DBS-STN implantation by 61.3% at 6 months and 55.4% at 3 years. STN-DBS allows for a reduction in the dosage of medication and the costs are similarly reduced. In this cohort different medication groups were reduced to a similar extent. Patients' demographic factors did not play a major role in the selection of treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.
    No preview · Article · Mar 2015 · Parkinsonism & Related Disorders
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    • "Models of compulsivity have emphasized the importance of DA tone in the ventral loops that link the ventral ACC and the VS/NAc in regulating reward and reinforcement behaviors (Fineberg et al., 2010; see Table 1). DA D2 receptor agonists such as levodopa have been associated with deficiencies in reversal learning (Cools et al., 2006), and increased compulsive behavior in Parkinson’s disease (Voon et al., 2009). Studies in animals have also shown that the administration of DA agonists induces stereotyped behaviors associated with OCD (Pitman, 1989). "
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    ABSTRACT: The compulsive nature of weight loss behaviors central to anorexia nervosa (AN), such as relentless self-starvation and over-exercise, has led to the suggestion of parallels between AN and other compulsive disorders such as obsessive-compulsive disorder (OCD) and addictions. There is a huge unmet need for effective treatments in AN, which has high rates of morbidity and the highest mortality rate of any psychiatric disorder, yet a grave paucity of effective treatments. Viewing compulsivity as a transdiagnostic concept, seen in various manifestations across disorders, may help delineate the mechanisms responsible for the persistence of AN, and aid treatment development. We explore models of compulsivity that suggest dysfunction in cortico-striatal circuitry underpins compulsive behavior, and consider evidence of aberrancies in this circuitry across disorders. Excessive habit formation is considered as a mechanism by which initially rewarding weight loss behavior in AN may become compulsive over time, and the complex balance between positive and negative reinforcement in this process is considered. The physiological effects of starvation in promoting compulsivity, positive reinforcement, and habit formation are also discussed. Further research in AN may benefit from a focus on processes potentially underlying the development of compulsivity, such as aberrant reward processing and habit formation. We discuss the implications of a transdiagnostic perspective on compulsivity, and how it may contribute to the development of novel treatments for AN.
    Full-text · Article · Jul 2014 · Frontiers in Psychology
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    • "Recent studies hypothesize that levodopa-induced dyskinesias (LIDs) and behavioral alterations observed in dopamine dysregulation syndrome and ICD2,18 depend on common mechanisms involving alterations of glutamate homeostasis with combined activation of sensitized dopamine and NMDA glutamatergic receptors.19 Pre- and postsynaptic mechanisms are implicated in the devolvement of LIDs and ICDs, the first based on alterations in dopamine transmission after chronic administrations and the second because of excessive expression and sensitization of D1 receptors in striatonigral neurons.2,20 The neuronal adaption underlying the imbalance between synaptic and nonsynaptic glutamate might result in failure of PC control. "
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    ABSTRACT: Introduction Dopamine replacement therapy for Parkinson’s disease (PD) was recently linked to the development of impulse control disorders such as pathological gambling (PG), hypersexuality, compulsive shopping, and binge or compulsive eating. Antiglutamatergic agents including amantadine (Ama) reduce these behaviors in PD and non-PD patients. The aim of our study is to evaluate the changes in executive functions, emotions, and reward/loss processing during Ama treatment in PD patients. Methods Thirty-three patients affected by idiopathic PD were selected from a cohort of 1,096 PD patients and categorized in three different groups: ten affected by PG (PD-PG); nine PD patients with other impulse control disorder (PD-ICD); and 14 PD patient without any psychiatric disorder (PD-CTR-controls). For the neuropsychological evaluation, the following behavioral tasks where administered: the Stroop, the emotional Stroop, and the monetary reward/loss risk-taking tasks. Results During Ama treatment, PD-PGs showed a decrease in risky choices and an increase in non-risky choices (t(9)=−2.40, P<0.05 and t(9)=2,67, P<0.05 uncorrected, respectively). Between-group comparison showed a significant decrease in risky choices for PD-PG with respect to PD-CTR (t(22)=−4.16, P<0.01), and a decreased accuracy for positive words in comparison between PD-PG and PD-ICD (t(17)=−7,49, P<0.01) and PD-PG and PD-CTR (t(22)=−4.29, P<0.01). No within- and between-group differences were observed for Stroop task. Discussion Our data showed that Ama add-on therapy reduces hypersensitivity to reward and sustains activation toward uncertainty in PD-PG patients. These finding might explain the behavioral mechanism underlying the effect of antiglutamatergic drugs.
    Full-text · Article · Jun 2014 · Neuropsychiatric Disease and Treatment
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