Risk factors for pathologic gambling and other compulsions among Parkinson’s disease patients taking dopamine agonists

Three hundred patients with Parkinson's disease taking dopamine agonists were surveyed for the presence of compulsions. Fifty-eight reported active compulsions which had developed after initiation of dopamine agonists. These included 25 with sexual compulsions and 28 with self-described compulsive gambling, of whom 17 met criteria for pathologic gambling. Males were over-represented. Patients with any compulsion and those with pathologic gambling were about 6 years younger than those without compulsions. These behavioral problems were not associated with an individual dopamine agonist, nor dose or duration, nor concomitant levodopa. Follow-up of the pathologic gamblers 1 year after intervention, which was cessation of the dopamine agonist in most cases, found ongoing but controlled gambling in five and complete cessation within 4 months in the remainder.     

Association of dopamine agonist use with impulse control disorders in Parkinson disease

OBJECTIVE: To determine the frequency and correlates of impulse control disorders (ICDs) in Parkinson disease (PD). DESIGN: An unstructured screening interview for ICDs (compulsive gambling, buying, and sexual behavior) followed by a telephone-administered structured interview for screen-positive patients. SETTING: Two university-affiliated movement disorders centers. PARTICIPANTS: A convenience sample of 272 patients with idiopathic PD who were screened for psychiatric complications. MAIN OUTCOME MEASURES: Presence of compulsive gambling, buying, or sexual behavior as assessed by the Minnesota Impulsive Disorders Interview. RESULTS: Eighteen patients (6.6%) with PD met criteria for an ICD at some point during the course of PD, including 11 (4.0%) with an active ICD. Compulsive gambling and compulsive sexual behavior were equally common. In a multivariate model, treatment with a dopamine agonist (P = .01) and a history of ICD symptoms prior to PD onset (P = .02) predicted current ICD. There were no differences between the dopamine agonists in their association with ICDs (P = .21), and daily doses of dopamine agonists were higher in patients with an ICD than in dopamine agonist-treated patients without an ICD (P < .001). CONCLUSIONS: Patients with PD treated with a dopamine agonist should be made aware of the risk of developing an ICD and monitored clinically. Because dopamine agonists are increasingly being used for other indications, future research should assess the dopamine agonist-associated risk for ICDs in other populations.     

Compulsive eating and weight gain related to dopamine agonist use.

Dopamine agonists have been implicated in causing compulsive behaviors in patients with Parkinson's disease (PD). These have included gambling, hypersexuality, hobbyism, and other repetitive, purposeless behaviors ("punding"). In this report, we describe 7 patients in whom compulsive eating developed in the context of pramipexole use. All of the affected patients had significant, undesired weight gain; 4 had other comorbid compulsive behaviors. In the 5 patients who lowered the dose of pramipexole or discontinued dopamine agonist treatment, the behavior remitted and no further weight gain occurred. Physicians should be aware that compulsive eating resulting in significant weight gain may occur in PD as a side-effect of dopamine agonist medications such as pramipexole. Given the known risks of the associated weight gain and obesity, further investigation is warranted.     

Association between the dose of dopaminergic medication and the behavioral disturbances in Parkinson disease

ObjectivesTo 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.MethodsA 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.ResultsAmong 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.ConclusionsThe dose of dopaminergic medication is significantly associated with the development of ICRB, except compulsive eating, in PD.     

Impulsive‐compulsive spectrum behaviors in pathologically confirmed progressive supranuclear palsy

There is growing awareness of impulsive‐compulsive spectrum behaviors (ICBs) in patients with Parkinson's disease (PD) treated with dopamine replacement therapy (DRT). These include pathological gambling, hypersexuality, compulsive shopping, binge eating, punding and compulsive use of DRT, or dopamine dysregulation syndrome. In PD, difficulties exist in separating the effects of DRT from the underlying disease process and aberrant dopaminergic systems in determining the aetiology of ICBs. Recent reports of ICBs associated with dopamine agonist use for conditions other than PD may suggest a significant etiological role for these medications, but currently published cases thus far lack pathological confirmation of diagnoses. We present three cases of pathologically confirmed progressive supranuclear palsy who developed ICBs in association with dopamine agonist use. Pathological comparisons between these three cases and other case series of progressive supranuclear palsy are made. © 2010 Movement Disorder Society     

Comparative neuropsychological profile of pathological gambling,hypersexuality, and compulsive eating in Parkinson's disease

Background: Impulse control disorders (ICDs), in particular pathological gambling, hypersexuality, and compulsive eating, are being increasingly identified in Parkinson's disease (PD) patients. Pathological gambling has been associated with frontal/executive dysfunctions, whereas hypersexuality and compulsive eating, and their relation with cognitive dysfunctions, have not been investigated in PD. Methods: We investigated cognitive correlates underpinning pathological gambling, hypersexuality, and compulsive eating in PD. PD outpatients were screened for pathological gambling, hypersexuality, and compulsive eating. Based on clinical criteria, we identified 13 patients with hypersexuality, 12 with compulsive eating, 14 with pathological gambling, and 10 with multiple ICDs. Fourteen PD patients matched for age and education without ICDs served as controls. Clinical features and neuropsychiatric and neuropsychological functioning were assessed in the 5 groups. Results: Demographic, clinical, neuropsychiatric, and neurological aspects did not differ among groups. All 4 groups of ICD patients were impaired on tasks exploring spatial‐planning and set‐shifting tasks compared with the controls. The main difference among patients with pathological gambling, hypersexuality, and compulsive eating was that patients with hypersexuality were more impaired on the Stroop test than patients with pathological gambling. Individuals with hypersexuality, compulsive eating, and multiple ICDs performed worse on verbal learning and memory tests than did patients with pathological gambling. Discussion: ICDs are associated with impaired cognitive functions; the severity of impairment decreased in the order multiple ICDs and hypersexuality > compulsive eating > pathological gambling. Our findings support the idea that hypersexuality is associated with prefrontal and memory dysfunctions, whereas pathological gambling seems to be related only to frontal dysfunction. © 2011 Movement Disorder Society     

Impulse control disorders and related behaviours (ICD-RBs) in Parkinson's disease patients: Assessment using “Questionnaire for impulsive-compulsive disorders in Parkinson's disease” (QUIP)

Background: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.Objectives: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).Results: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.Conclusions: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.     

Impulse control disorders in parkinson’s disease

There is an increasing awareness that impulse control disorders (ICDs), including pathologic gambling and compulsive sexual behavior, can occur as a complication of Parkinson’s disease (PD). Anecdotal experience and case reporting have suggested an association between ICDs in PD and the use of dopamine agonists. Lacking established treatments for ICDs in PD, clinical management should initially consist of modifications to or discontinuation of dopamine replacement therapy, particularly dopamine agonists. It is important that PD patients be aware that dopamine agonist use may lead to the development of an ICD, and that clinicians monitor patients as part of routine clinical care. As empirically validated treatments for ICDs are emerging, it will be important to examine their efficacy and tolerability in individuals with co-occurring PD and ICDs.     

Pathological gambling caused by drugs used to treat Parkinson disease

BACKGROUND: Pathological gambling is a rare potential complication related to treatment of Parkinson disease (PD). However, the etiology of this behavior is poorly understood. OBJECTIVE: To examine the relationship between medical therapy for PD and pathological gambling. METHODS: In our routine movement disorders practice (2002-2004), we encountered 11 patients with idiopathic PD who had recently developed pathological gambling. We assessed the relationship to their medical therapy and compared them with cases identified by systematic review of the existing literature on pathological gambling and PD. RESULTS: All 11 patients with PD and pathological gambling were taking therapeutic doses of a dopamine agonist; 3 of these patients were not treated with levodopa. In 7 patients, pathological gambling developed within 3 months of starting to take or escalating the dose of the agonist; in the other 4 with a longer latency, gambling resolved after the agonist use was discontinued. Pramipexole dihydrochloride was the agonist in 9 of 11 cases in our series and 10 of 17 in the literature (68% in total). CONCLUSIONS: Dopamine agonist therapy was associated with potentially reversible pathological gambling, and pramipexole was the medication predominantly implicated. This may relate to disproportionate stimulation of dopamine D(3) receptors, which are primarily localized to the limbic system.     

Pathological gambling amongst Parkinson's disease and ALS patients in an online community (PatientsLikeMe.com)

Pathological gambling (PG) has been identified in Parkinson's disease (PD), but such gambling behaviors may also occur in amyotrophic lateral sclerosis (ALS). We sought to estimate the prevalence of PG amongst members of a web‐based community, PatientsLikeMe.com. A survey was constructed, consisting of demographic information, the South Oaks Gambling Screen (SOGS), the K‐6 measure of distress, and items related to motivation for gambling. Data were obtained from 236 ALS patients and 208 PD patients. Of the PD patients, 13% were classified as problem gamblers compared with 3% of ALS patients (χ² = 14.005, P ≤ 0.001). PD patients reported thoughts about gambling to be more distressing, harder to resist and more outside their control than ALS patients. Thus, the higher prevalence of compulsive behavior in PD may relate to damaged reward pathways or medication rather than to the effects of living with a chronic progressive neurological disorder per se. © 2009 Movement Disorder Society     

Impulsive smoking in a patient with Parkinson’s disease treated with dopamine agonists

Impulse control disorders, including pathological gambling, binge eating, compulsive shopping and hypersexual behaviors, have frequently been reported as a side effect of dopaminergic medications for Parkinson’s disease (PD). Here we describe a patient with PD who developed an unusual manifestation of impulsive behaviors, including cigarette smoking, associated with an increase in dopamine agonist medication. We postulate this to be related to an overstimulation of mesolimbic dopamine receptors responsible for reward-seeking behaviors. Further research is needed to examine impulsive cigarette smoking in PD.     

The relationship between impulsivity and impulse control disorders in Parkinson's disease

A range of behaviors presumed to be related to dopaminergic medications have been recently recognized in Parkinson's disease (PD). We evaluated 50 consecutive cognitively intact PD patients on stable dopamine agonist and levodopa therapy and 100 healthy controls for compulsive sexual behavior, compulsive buying, or intermittent explosive disorders assessed by the Minnesota Impulsive Disorders Interview (MIDI), pathological gambling (South Oaks Gambling Screen, SOGS), impulsivity (Barratt Impulsiveness Scale), compulsivity (Maudsley obsessional‐compulsive inventory), and depression scores (Geriatric Depression Scale). Overall 28% PD (14/50) and 20% healthy controls (20/100) reported at least one abnormal behavior at MIDI or pathological SOGS score. PD patients had higher scores than controls for impulsivity (P = 0.006), compulsivity (P < 0.001), and depression (P < 0.001). There was no correlation between impulsivity, compulsivity, and depression scores in PD. Male gender and higher impulsivity score, but not dose and kind of dopaminergic medications, were associated in PD with increased probability of impulsive disorders at MIDI. Impulse control disorders are also common in the control population. Individual susceptibility factors, such as high impulsivity and depression, underline abnormal behaviors in PD patients treated with stable dopaminergic therapy. © 2007 Movement Disorder Society     

Amantadine use associated with impulse control disorders in Parkinson disease in cross-sectional study

A recent controlled clinical trial suggested a role for amantadine as a treatment for pathological gambling in patients with Parkinson disease (PD). Analyzing data from a large cross-sectional study of impulse control disorders (ICDs) in PD, amantadine use (n = 728), vs no amantadine use (n = 2,357), was positively associated with a diagnosis of any ICD (17.6% vs 12.4%, p < 0.001) and compulsive gambling specifically (7.4% vs 4.2%, p < 0.001). This amantadine association remained after controlling for covariates of amantadine use, including both dopamine agonist use and levodopa dosage. Further research, including larger clinical trials, is needed to assess the role of amantadine in the development and treatment of ICDs in PD.     

Attention-deficit-hyperactivity disorder and reward deficiency syndrome

Molecular genetic studies have identified several genes that may mediate susceptibility to attention deficit hyperactivity disorder (ADHD). A consensus of the literature suggests that when there is a dysfunction in the “brain reward cascade,” especially in the dopamine system, causing a low or hypo-dopaminergic trait, the brain may require dopamine for individuals to avoid unpleasant feelings. This high-risk genetic trait leads to multiple drug-seeking behaviors, because the drugs activate release of dopamine, which can diminish abnormal cravings. Moreover, this genetic trait is due in part to a form of a gene (DRD₂ A1 allele) that prevents the expression of the normal laying down of dopamine receptors in brain reward sites. This gene, and others involved in neurophysiological processing of specific neurotransmitters, have been associated with deficient functions and predispose individuals to have a high risk for addictive, impulsive, and compulsive behavioral propensities. It has been proposed that genetic variants of dopaminergic genes and other “reward genes” are important common determinants of reward deficiency syndrome (RDS), which we hypothesize includes ADHD as a behavioral subtype. We further hypothesize that early diagnosis through genetic polymorphic identification in combination with DNA-based customized nutraceutical administration to young children may attenuate behavioral symptoms associated with ADHD. Moreover, it is concluded that dopamine and serotonin releasers might be useful therapeutic adjuncts for the treatment of other RDS behavioral subtypes, including addictions.     

Neuroendocrine response to casino gambling in problem gamblers

Problematic gambling is thought to be influenced by neurobiological mechanisms. However, the neuroendocrine response to gambling is largely unknown. Therefore, the effect of casino gambling on the sympathoadrenal system, the HPA-axis, and pituitary hormones were analyzed.

Fourteen male problem gamblers and 15 non-problem gamblers were examined in a balanced cross-over design. In the experimental session, participants played blackjack in a casino wagering their own money. During the control session, subjects played cards for accumulation of points. Heart rate and endocrine measures were recorded at baseline, at 30, 60 and 90 min during gambling/card playing, and after the game.

Heart rate and norepinephrine levels increased with the onset of blackjack in both groups, with problem gamblers showing significantly higher levels across the entire gambling session. In addition, dopamine levels were significantly higher in problem gamblers during casino gambling compared to non-problem gamblers. Cortisol levels were transiently increased with the onset of blackjack in both groups.

Casino gambling as a “real life” situation induces activation of the HPA-axis and the sympathoadrenergic system, with significantly more pronounced changes in problem gamblers. These findings may contribute to a better understanding of neuroendocrine disturbances in problem gambling.     

Types of Medication-Assisted Treatment for Opioid Use Disorder in Turkey: The Perceptions of Inpatients about Treatment Success

ObjectiveThe aim of this study was the following. When the different dynamics of agonist or antagonist treatments considered it is assumed that the eligible treatment to the individual may be maintained with high efficacy. Thus, we aimed to examine the difference between treatment methods, considering sociodemographics and positive perception for treatment success. MethodsThe number of 136 individuals which their ages range between 19–50 and have been getting agonist (buprenorphine/naloxone) or antagonist (naltrexone) treatment because of opioid use disorder while resting in clinics have been evaluated to reveal the factors that may alter their perception about treatment and have been compared with sociodemographic variables and characteristics such as sociotropic and autonomic. Therefore, “Sociodemographic Data Evaluation Form,” “Predictive Factors for The Addiction Treatment Success Scale,” and “Sociotropy-Autonomy Scale” were used to assess the sociodemographic data, the perception towards factors which have been affected to the treatment and characteristics. The data of the individuals have been collected by the researcher via face-to-face interviews while patients were residential in the clinic. ResultsAccording to results of our study, it has been detected that there are some differences in the perception of treatment success between individuals who have been getting agonist or antagonist treatments such as treatment method (p<0.05), treatment frequency (p<0.01) and parents’ vital statuses (p<0.05). ConclusionAt the end of the study it has been understood that medical and social benefits after the selection of eligible treatment methods which is suitable for individual’s perception and characteristics have to be considered.     

Reduced cortical folding of the anterior cingulate cortex in obsessive–compulsive disorder

Background

Anterior cingulate cortex (ACC) abnormalities have been implicated consistently in the pathophysiology of obsessive–compulsive disorder (OCD), yet it remains unclear whether these abnormalities originated during early neurodevelopment. In this study, we examined the ACC sulcal/gyral patterns to investigate whether neurodevelopmental anomalies of the ACC were present in patients with OCD. We hypothesized that patients with OCD would show reduced cortical folding of the ACC compared with controls.

Methods

We used magnetic resonance imaging (MRI) of 169 healthy volunteers and 110 patients with OCD to examine the paracingulate sulcus and cingulate sulcus. We assessed cortical folding patterns according to established classification criteria and constructed 3 categories of paracingulate sulcus morphology according to its presence and anteroposterior extent: “prominent,” “present” and “absent.” We classified the cingulate sulcus as “interrupted” or “continuous” according to the interruptions in its course. In addition, we evaluated ACC sulcal asymmetry based on interhemispheric comparisons of paracingulate sulcus morphology.

Results

Analyses revealed that patients with OCD were significantly less likely than controls to show a well-developed left paracingulate sulcus: 50.0% of patients and 65.1% of controls showed a “prominent” or “present” paracingulate sulcus in the left hemisphere. However, there were no differences in regard to cingulate sulcus continuity, and patients also showed the same leftward ACC sulcal asymmetry as controls.

Limitations

Our study was limited by the fact that we obtained the MRI scans from 2 different scanners, and we did not calculate cerebral fissurization as our study was restricted to 1 specific brain region. Moreover, patients and controls differed significantly in terms of sex ratio and IQ, although we controlled these variables as covariates.

Conclusion

Our findings imply a subtle deviation in the early neurodevelopment of the ACC in patients with OCD, but the extent to which these anomalies contributed to the pathogenesis of OCD remains unclear. Further studies that link the ACC morphologic anomalies to the pathophysiology of OCD are recommended.     

Impulsive and compulsive behaviors in Parkinson's disease: a one-year follow-up study

Impulsive and compulsive behaviors (ICBs) have been reported to occur frequently in Parkinson's disease (PD) and include impulse control disorders (ICDs), punding and dopamine dysregulation syndrome (SSD). We report on the outcomes of 25 PD patients who developed ICBs. Information was collected on changes in parkinsonian and psychiatric medication follow-up (median=12.1 months). At time 1, only 18 patients (72%) were taking dopamine agonists (DA). At time 2, fifteen patients (83.33%) either discontinued or decreased their DA treatment. Of these patients, thirteen (86.67%) reported experiencing full or partial remission of their ICBs symptoms. When analyzing separately the 11 patients with punding, these symptoms remained unchanged in 9 patients (81.82%) independently of changes in dopaminergic drugs. In conclusion, the current study suggests that there are clear similarities, but also important differences, between punding and ICDs over time. Pathological gambling, binge or compulsive eating, pathological hypersexuality and compulsive shopping in PD were robustly associated with the use of DA but the relationship between dopaminergic medications and punding is less clear. It is important to determine if other treatment strategies may be effective for punding in PD.     

Psychotic and compulsive symptoms in Parkinson's disease

The objective of this study is to evaluate psychiatric symptoms in Parkinson's disease (PD) patients and to assess their relation with other clinical aspects of PD. Psychotic symptoms (PS) and compulsive symptoms (CS) as well as other nonmotor and motor features were evaluated in 353 PD patients. Psychotic and compulsive symptom scores did not correlate significantly. PS occurred in 65% of patients, with item frequencies ranging from 10% (paranoid ideation) to 55% (altered dream phenomena). Regression analysis showed that autonomic impairment accounted for 20% of the 32% explained variance of PS, whereas cognitive problems, depression, daytime sleepiness, and dopamine agonist (DA) dose explained the rest. CS occurred in 19%, with item frequencies of 10% for both sexual preoccupation and compulsive shopping/gambling. Patients with more severe CS (score ≥ 2 on one or both items) were significantly more often men, had a younger age at onset, a higher DA dose and experienced more motor fluctuations compared to the other patients. PS and CS are common but unrelated psychiatric symptoms in PD. The relations found between PS and cognitive problems, depression, daytime sleepiness, and autonomic impairment suggests a resemblance with Dementia with Lewy Bodies. The prominent association between PS and autonomic impairment may be explained by a shared underlying mechanism. Our results confirm previous reports on the profile of patients developing CS, and mechanisms underlying motor fluctuations may also play a role in the development of CS in PD. © 2009 Movement Disorder Society     

Tracking online poker problem gamblers with player account‐based gambling data only

The aim was to develop and validate an instrument to track online problem poker gamblers with player account‐based gambling data (PABGD). We emailed an invitation to all active poker gamblers on the online gambling service provider Winamax. The 14,261 participants completed the Problem Gambling Severity Index (PGSI). PGSI served as a gold standard to track problem gamblers (i.e., PGSI ≥ 5). We used a stepwise logistic regression to build a predictive model of problem gambling with PABGD, and validated it. Of the sample 18% was composed of online poker problem gamblers. The risk factors of problem gambling included in the predictive model were being male, compulsive, younger than 28 years, making a total deposit > 0 euros, having a mean loss per gambling session > 1.7 euros, losing a total of > 45 euros in the last 30 days, having a total stake > 298 euros, having > 60 gambling sessions in the last 30 days, and multi‐tabling. The tracking instrument had a sensitivity of 80%, and a specificity of 50%. The quality of the instrument was good. This study illustrates the feasibility of a method to develop and validate instruments to track online problem gamblers with PABGD only. Copyright © 2016 John Wiley & Sons, Ltd.