Article

Clozapine for Medication-Related Pathological Gambling in Parkinson Disease

Movement Disorders (Impact Factor: 5.63). 09/2010; 25(12):1994-5. DOI: 10.1002/mds.23177
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    • "Controversial results (Kurlan, 2004; Raja and Bentivoglio, 2012) Clozapine D 4 R and 5- HT 2A antagonist ▼ in a doble-blind placebo-controled trial (Durif et al., 2004) ▼ PG in a case report (Rotondo et al., 2010) ▼ DDS in a retrospective case-control study (Cilia et al., 2014) "
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    ABSTRACT: Dopaminergic treatment in Parkinson's disease (PD) reduces the severity of motor symptoms of the disease. However, its chronic use is associated with disabling motor and behavioural side effects, among which levodopa-induced dyskinesias (LID) and impulse control disorders (ICD) are the most common. The underlying mechanisms and pathological substrate of these dopaminergic complications are not fully understood. Recently, the refinement of imaging techniques and the study of the genetics and molecular bases of LID and ICD indicate that, although different, they could share some features. In addition, animal models of parkinsonism with LID have provided important knowledge about mechanisms underlying such complications. In contrast, animal models of parkinsonism and abnormal impulsivity, although useful regarding some aspects of human ICD, do not fully resemble the clinical phenotype of ICD in patients with PD, and until now have provided limited information. Studies on animal models of addiction could complement the previous models and provide some insights into the background of these behavioural complications given that ICD are regarded as behavioural addictions. Here we review the most relevant advances in relation to imaging, genetics, biochemistry and pharmacological interventions to treat LID and ICD in patients with PD and in animal models with a view to better understand the overlapping and unique maladaptations to dopaminergic therapy that are associated with LID and ICD. Copyright © 2015. Published by Elsevier Ltd.
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    • "Moreover , the notion of the so-called DAA withdrawal syndrome (DAWS)––defined as psychological (e.g., anxiety, panic attacks, depression) or physical (e.g., diaphoresis, orthostatic hypotension) symptoms caused by the tapering of DAAs (Rabinak and Nirenberg 2010; Schlesinger et al. 2010)––underscores an urgent need for more therapeutic options for the clinician. Although case reports suggest possible roles for subthalamic stimulation (Bandini et al. 2007; Halbig et al. 2009) (but see Moro 2009), enteral carbidopa/levodopa infusions, amantadine, zonisamide, carbamazepine or clozapine (Bach et al. 2009; Bermejo et al. 2010; Gerschlager and Bloem 2009; Rotondo et al. 2010; Thomas et al. 2010), none of these potential add-on medications have been tested in prospective, randomized controlled trials. It is also worth mentioning that SSRI medications are commonly used in the treatment of nonparkinsonian ICDs and that opioid antagonists also seem to be effective (Leung and Cottler 2009), probably by increasing punishment sensitivity (Petrovic et al. 2008). "
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    ABSTRACT: The development of an impulse control disorder (ICD) is now recognized as a potential nonmotor adverse effect of dopamine replacement therapy in Parkinson's disease (PD). Here, recent epidemiological, neurophysiological and genetic advances are summarized to outline potential mechanisms involved. It is safe to say that dopaminergic drugs, particularly dopamine agonists, are able to induce ICDs only in a minority of patients, while the majority are somehow protected from this adverse effect. While it seems clear that men with early-onset PD are more vulnerable, other predisposing factors, such as various current or pre-PD personality traits, are a matter of debate. In terms of neurophysiological advances, one may find striking analogies to the addiction literature suggesting a causal chain beginning with certain predisposing conditions of striatal dopamine synapses, an "unnatural" increase of dopamine stimulation and a characteristic pattern of resulting functional changes in remote networks of appetitive drive and impulse control. Future prospects include potential add-on medications and the possible identification of genetic predispositions at a genome-wide scale. Functional imaging of pharmacogenetic interactions (imaging pharmacogenomics) may be an important tool on that road.
    Brain Structure and Function 05/2011; 216(4):289-99. DOI:10.1007/s00429-011-0314-0 · 4.57 Impact Factor
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    ABSTRACT: Although the cardinal manifestations of Parkinson's disease (PD) are attributed to a decline in dopamine levels in the striatum, a breadth of non-motor features and treatment-related complications in which the serotonergic system plays a pivotal role are increasingly recognised. Serotonin (5-HT)-mediated neurotransmission is altered in PD and the roles of the different 5-HT receptor subtypes in disease manifestations have been investigated. The aims of this article are to summarise and discuss all published preclinical and clinical studies that have investigated the serotonergic system in PD and related animal models, in order to recapitulate the state of the current knowledge and to identify areas that need further research and understanding.
    Progress in Neurobiology 08/2011; 95(2):163-212. DOI:10.1016/j.pneurobio.2011.08.004 · 10.30 Impact Factor
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