Impulse control symptoms in patients with Parkinson's disease: The influence of dopaminergic agonist

Vargas, Antônio Pedro; Vaz, Luiz Sérgio; Reuter, Alex; Couto, Christian Marques; Cardoso, Francisco

doi:10.1016/j.parkreldis.2019.06.019

Cited by 15 publications

(9 citation statements)

References 26 publications

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“…The observed cases of impulse control disorders and punding were all mild in severity and some were reversible, with a relatively low incidence (less than 10% of patients). These findings are in keeping with other reports for APO infusion [20,21], suggesting better tolerability than reported for oral dopamine agonists [22,23], although the duration of the observation period and the lack of a direct comparison limit conclusions.…”

Section: Discussionsupporting

confidence: 90%

Long-term safety and efficacy of apomorphine infusion in Parkinson's disease patients with persistent motor fluctuations: Results of the open-label phase of the TOLEDO study

Katzenschlager

Poewe

Rascol

et al. 2021

Parkinsonism & Related Disorders

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The randomized, double-blind phase (DBP) of the TOLEDO study confirmed the efficacy of apomorphine infusion (APO) in reducing OFF time in PD patients with persistent motor fluctuations despite optimized oral/transdermal therapy. Here we report safety and efficacy results including the 52-week open-label phase (OLP). Methods: All patients completing the 12-week DBP (including those switching early to open-label treatment) were offered OLP entry. The primary objective was the evaluation of long-term safety of APO. Results: Eighty-four patients entered the OLP (40 previously on APO, 44 on placebo) and 59 patients (70.2%) completed the study. The safety profile of APO was consistent with experience from extensive clinical use. Common treatment-related adverse events (AEs) were mild or moderate infusion site nodules, somnolence and nausea. Fourteen (16.7%) patients discontinued the OLP due to AEs, those involving >1 patient were infusion site reactions (n = 4) and fatigue (n = 2); hemolytic anemia occurred in one case. Reduction in daily OFF time and improvement in ON time without troublesome dyskinesia were sustained for up to 64 weeks. Pooled data for week 64 (n = 55) showed a mean (SD) change from DBP baseline in daily OFF time of − 3.66 (2.72) hours and in ON time without troublesome dyskinesia of 3.31 (3.12) hours. Mean (±SD) daily levodopa-equivalent dose decreased from DBP baseline to week 64 by 543 mg (±674) and levodopa dose by 273 mg (±515). Conclusions: The safety and efficacy of APO infusion were demonstrated with long-term use for persistent motor fluctuations, allowing substantial reductions in oral PD medication.

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Section: Discussionsupporting

confidence: 90%

Long-term safety and efficacy of apomorphine infusion in Parkinson's disease patients with persistent motor fluctuations: Results of the open-label phase of the TOLEDO study

Katzenschlager

Poewe

Rascol

et al. 2021

Parkinsonism & Related Disorders

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“…Taken together, and considering in particular data involving drug‐naive PD patients, all these findings suggest that susceptibility of PD patients to ICB development might be related to a preexisting biological predisposition, for which the use of dopaminergic medications could act by modulating relevant networks, including striatocortical and limbic circuits. Accordingly, a recent study analyzing data from the Parkinson's Progression Markers Initiative failed to demonstrate increased risk for the development of ICBs in PD patients in the absence of treatment, and Vargas and colleagues, by conducting a case–control study on 207 PD patients (79 taking dopamine agonists) and 230 healthy controls, showed that PD pathology itself does not lead to the development of ICBs, but dopaminergic agonist treatment may trigger the disorder in susceptible subjects …”

Section: Resultsmentioning

confidence: 99%

MRI of Motor and Nonmotor Therapy‐Induced Complications in Parkinson's Disease

2020

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Levodopa therapy remains the most effective drug for the treatment of Parkinson's disease, and it is associated with the greatest improvement in motor function as assessed by the Unified Parkinson's Disease Rating Scale. Dopamine agonists have also proven their efficacy as monotherapy in early Parkinson's disease but also as adjunct therapy. However, the chronic use of dopaminergic therapy is associated with disabling motor and nonmotor side effects and complications, among which levodopa‐induced dyskinesias and impulse control behaviors are the most common. The underlying mechanisms of these disorders are not fully understood. In the last decade, classic neuroimaging methods and more sophisticated techniques, such as analysis of gray‐matter structural imaging and functional magnetic resonance imaging, have given access to anatomical and functional abnormalities, respectively, in the brain. This review presents an overview of structural and functional brain changes associated with motor and nonmotor therapy‐induced complications in Parkinson's disease. Magnetic resonance imaging may offer structural and/or functional neuroimaging biomarkers that could be used as predictive signs of development, maintenance, and progression of these complications. Neurophysiological tools, such as theta burst stimulation and transcranial magnetic stimulation, might help us to integrate neuroimaging findings and clinical features and could be used as therapeutic options, translating neuroimaging data into clinical practice. © 2020 International Parkinson and Movement Disorder Society

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“…2.6%) compared to ICD rates in general (max. 19.0%); ICD frequencies were lower under rotigotine treatment compared to most other DAs Erga et al, 2017 [ 151 ] Norway Cross-sectional study; 125 patients with PD, 159 age- and gender-matched controls Levodopa, DAs Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease (QUIP) 1.6% GD rate in PD patients, 0.6% in controls; ICD patients were more likely to take DAs without a dose-dependent effect Corvol et al, 2018 [ 152 ] France Multicentral, prospective cohort study (5 y); 411 patients with early PD Levodopa, DAs Semi-structured interviews for the diagnosis of compulsive gambling according to DSM-IV DAs are strongly associated with ICDs with a dose-effect relationship, levodopa only mildly El Otmani et al, 2019 [ 153 ] Morocco Cross-sectional study; 125 patients with PD Levodopa, DAs Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease-Rating Scale (QUIP-RS) 3.2% GD rate; no class differences between DAs Vargas et al, 2019 [ 154 ] Brazil Case-control study; 207 patients with PD, 230 healthy controls Levodopa, DAs Interviews with patients and relatives according to DSM-IV GD frequency was 4.8% in PD patients and 1.3% in controls; ICDs are more common under DA treatment (27.8% vs. 10.2%) Holman et al, 2009 [ 124 ] USA Retrospective study of patient charts; 3006 patients with fibromyalgia DAs Clinical interviews according to DSM-IV Seven cases of GD under pramipexole treatment; resolved with discontinued treatment after 3–10 days or max. 3 months Cornelius et al, 2010 [ 155 ] USA Prospective case–control study; 100 patients with RLS under DA treatment with 327 control patients DAs Modified version of the South Oaks Gambling Screen and interviews The RLS patients under DA treatment had a higher frequency of GD (7% or 5%) compared to the non-RLS patients (1% or 0.4%) and the RLS group without DA treatment (2% or 2%); there was a dose effect for pramipe...…”

Section: Drug-induced Changes In Gdmentioning

confidence: 99%

Drug-Induced Gambling Disorder: Epidemiology, Neurobiology, and Management

Wolfschlag

Håkansson

2023

Pharm Med

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Problematic gambling has been suggested to be a possible consequence of dopaminergic medications used mainly in neurological conditions, i.e. pramipexole and ropinirole, and possibly by one antipsychotic compound, aripiprazole. Patients with Parkinson’s disease, restless legs syndrome and other conditions potentially treated with dopamine agonists, as well as patients treated for psychotic disorders, are vulnerable patient groups with theoretically increased risk of developing gambling disorder (GD), for example due to higher rates of mental ill-health in these groups. The aim of the present paper is to review the epidemiological, clinical, and neurobiological evidence of the association between dopaminergic medications and GD, and to describe risk groups and treatment options. The neurobiology of GD involves the reward and reinforcement system, based mainly on mesocorticolimbic dopamine projections, with the nucleus accumbens being a crucial area for developing addictions to substances and behaviors. The addictive properties of gambling can perhaps be explained by the reward uncertainty that activates dopamine signaling in a pathological manner. Since reward-related learning is mediated by dopamine, it can be altered by dopaminergic medications, possibly leading to increased gambling behavior and a decreased impulse control. A causal relationship between the medications and GD seems likely, but the molecular mechanisms behind this association have not been fully described yet. More research is needed in order to fully outline the clinical picture of GD developing in patient groups with dopaminergic medications, and data are needed on the differentiation of risk in different compounds. In addition, very few interventional studies are available on the management of GD induced by dopaminergic medications. While GD overall can be treated, there is need for treatment studies testing the effectiveness of tapering of the medication or other gambling-specific treatment modalities in these patient groups.

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Impulse control symptoms in patients with Parkinson's disease: The influence of dopaminergic agonist

Cited by 15 publications

References 26 publications

Long-term safety and efficacy of apomorphine infusion in Parkinson's disease patients with persistent motor fluctuations: Results of the open-label phase of the TOLEDO study

Long-term safety and efficacy of apomorphine infusion in Parkinson's disease patients with persistent motor fluctuations: Results of the open-label phase of the TOLEDO study

MRI of Motor and Nonmotor Therapy‐Induced Complications in Parkinson's Disease

Drug-Induced Gambling Disorder: Epidemiology, Neurobiology, and Management

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