Association between the dose of dopaminergic medication and the behavioral disturbances in Parkinson disease
ABSTRACT To survey the point prevalence of impulse control and repetitive behavior disorders (ICRBs) in patients with Parkinson disease (PD) and to determine the relationship between PD medication dose and the risk of ICRBs.
A multicenter cross-sectional survey was applied to consecutive patients with PD over a 3-month period. The presence of ICRBs was screened using a modified version of the Minnesota Impulsive Disorders Interview that comprised five ICRB modules: compulsive buying, gambling, sexual behavior, eating, and punding. Data regarding the patients' clinical features and concurrent anti-PD drugs were also collected during the interview. Adjusted odds ratios (ORs) of the daily doses of dopamine agonist and L-dopa for the development of an ICRB were calculated after adjustment for clinical variables.
Among the 1167 patients recruited, 118 (10.1%) exhibited ICRBs. Punding was the most common ICRB (4.2%), followed by compulsive eating (3.4%), sexual behaviors (2.8%), buying (2.5%), and gambling (1.3%). Two or more ICRBs were present concomitantly in 34 of these 118 patients (28.8%). There were dose-response relationships between the dopamine agonist dose and the ORs for compulsive buying, gambling and sexual behaviors. On the other hand, the OR for punding was positively correlated with the dose of L-dopa. The OR for compulsive eating was not associated with the dose of dopamine agonist or L-dopa.
The dose of dopaminergic medication is significantly associated with the development of ICRB, except compulsive eating, in PD.
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ABSTRACT: The aim of this study was to determine the changes in diffusion-tensor images associated with medication-related impulse control disorder (ICD) in Parkinson's disease (PD) patients undergoing chronic dopamine-replacement therapy. Nineteen PD patients, comprising 10 with ICD (PD-ICD) and 9 without ICD (PD-nonICD), and 18 age-matched healthy controls (HCs) with no cognitive or other psychiatric disorders were analyzed. All subjects underwent 3-T magnetic resonance diffusion-tensor imaging. For all PD patients, clinical data on PD duration, antiparkinsonian medication dosages, Unified Parkinson's Disease Rating Scale and Mini-Mental State Examination were collected. Whole-brain voxel-based measures of fractional anisotropy (FA) and mean diffusivity (MD) were analyzed. In comparison with HCs, the PD-nonICD subjects had low FA at the bilateral orbitofrontal areas. While the PD-ICD subjects exhibited no such difference, their FA was significantly elevated at the anterior corpus callosum. Analysis of FA between the two PD groups revealed that FA in the anterior corpus callosum, right internal capsule posterior limbs, right posterior cingulum, and right thalamic radiations were significantly higher (corrected p<0.05) in the PD-ICD than in the PD-nonICD patients. MD did not differ between the PD-ICD and PD-nonICD groups in any brain regions. The PD-ICD patients appear to have relatively preserved white-matter integrity in the regions involved in reward-related behaviors compared to PD-nonICD patients. Further investigation is required to determine whether the difference in FA between PD-ICD and PD-nonICD patients reflects microstructural differences in the pathological progression of PD or is secondary to ICD.Journal of Clinical Neurology 01/2015; 11(1):42-7. DOI:10.3988/jcn.2015.11.1.42 · 1.81 Impact Factor
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ABSTRACT: Background: Impulsive and compulsive behaviors (ICBs) are a heterogeneous group of conditions that may be caused by long-term dopaminergic replacement therapy (DRT) of Parkinson’s disease (PD). The spectrum of ICBs includes dopamine dysregulation syndrome (DDS), punding, and impulse control disorders (ICDs). Contents: We made a detailed review regarding the epidemiology, pathology, clinical characteristics, risk factors, diagnosis as well as treatment of ICBs. Results: The prevalence of ICBs in PD patients is approximately 3–4% for DDS, 0.34–4.2% for punding, and 6–14% for ICDs, with higher prevalence in Western populations than in Asian. Those who take high dose of levodopa are more prone to have DDS, whereas, ICDs are markedly associated with dopamine agonists. Different subtypes of ICBs share many risk factors such as male gender, higher levodopa equivalent daily dose, younger age at PD onset, history of alcoholism, impulsive, or novelty-seeking personality. The Questionnaire for Impulsive–Compulsive Disorder in Parkinson’s Disease-Rating Scale seems to be a rather efficacious instrument to obtain relevant information from patients and caregivers. Treatment of ICBs is still a great challenge for clinicians. Readjustment of DRT remains the primary method. Atypical antipsychotics, antidepressants, amantadine, and psychosocial interventions are also prescribed in controlling episodes of psychosis caused by compulsive DRT, but attention should be drawn to balance ICBs symptoms and motor disorders. Moreover, deep brain stimulation of the subthalamic nucleus might be a potential method in controlling ICBs. Conclusion: The exact pathophysiological mechanisms of ICBs in PD remains poorly understood. Further researches are needed not only to study the pathogenesis, prevalence, features, and risk factors of ICBs, but to find efficacious therapy for patients with these devastating consequences.Frontiers in Aging Neuroscience 11/2014; 6:318. DOI:10.3389/fnagi.2014.00318 · 2.84 Impact Factor
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ABSTRACT: There is limited data on the prevalence of impulse control disorder and related behaviors (ICD-RBs) in Indian patients with Parkinson's Disease (PD). In the context of potential genetic and environmental factors affecting the expression of ICD-RBs, studying other multiethnic populations may bring in-sights into the mechanisms of these disorders. To ascertain point prevalence estimate of ICD-RBs in Indian PD patients, using the validated "Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease (QUIP)" and to examine their association with Dopamine replacement therapy (DRT). This was a hospital based observational cross-sectional study. After taking informed consent, patients and their informants (spouse, or primary caregiver) were made to complete the QUIP, and were instructed to answer questions based on behaviors that occurred anytime during PD that lasted at least four consecutive weeks. Total of 299 patients participated in the study. At least one ICD-RB was present in 128 (42.8%), at least one Impulse control disorder (ICD) was present in 74 (24.75%) and at least one Impulse control related compulsive behaviour (ICRB) was present in 93 (31.1%) patients. Punding was the most frequent (12.4%) followed by hyper sexuality (11.04%), compulsive hobbyism (9.4%), compulsive shopping (8.4%), compulsive medication use (7.7%), compulsive eating (5.35%), walkabout (4%) and pathological gambling (3.3%). ≥ 2 ICD-RBs were observed in 15.7% of patients. After multivariate analysis, younger age of onset, being unmarried were specifically associated with presence of ICD. Longer disease duration was specifically associated with presence of ICRB. Whereas smoking and higher dopamine levodopa equivalent daily doses (DA LEDD) were associated with both presence of ICD and ICRB. Higher LD LEDD was specifically associated with presence of ICD-RB. Our study revealed a relatively higher frequency of ICD-RBs, probably because of the use of screening instrument and because we combined both ICDs and ICRBs. Also high proportion of DA use (81.6%) among our patients might be responsible. The role of genetic factors that might increase the risk of developing ICD-RBs in this population needs further exploration.Annals of Indian Academy of Neurology 01/2015; 18(1):49-59. DOI:10.4103/0972-2327.144311 · 0.51 Impact Factor