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1.  Impulse control disorders and compulsive behaviors associated with dopaminergic therapies in Parkinson disease 
Neurology. Clinical Practice  2012;2(4):267-274.
Summary
Impulse control disorders (ICD) (most commonly pathologic gambling, hypersexuality, and uncontrollable spending) and compulsive behaviors can be triggered by dopaminergic therapies in Parkinson disease (PD). ICD are especially prevalent in patients receiving a dopamine agonist as part of their treatment regimen for PD, and have also been reported when dopamine agonists are used for other indications (e.g., restless legs syndrome). Although these iatrogenic disorders are common, affecting 1 in 7 patients with PD on dopamine agonists, they often elude detection by the treating physician. ICD lead to serious consequences, causing significant financial loss and psychosocial morbidity for many patients and families. ICD can appear at any time during treatment with dopamine agonists, sometimes within the first few months, but most often after years of treatment, particularly when patients receive dopamine agonists and levodopa together. In most cases ICD resolve if the dopamine agonist is withdrawn, and PD motor symptoms are managed with levodopa monotherapy. Familiarity with the clinical aspects, risk factors, pathophysiology, and management of ICD is essential for physicians using dopaminergic therapies to treat PD and other disorders.
doi:10.1212/CPJ.0b013e318278be9b
PMCID: PMC3613210  PMID: 23634371
2.  Dopamine and Impulse Control Disorders in Parkinson’s Disease 
Annals of neurology  2008;64(Suppl 2):S93-100.
There is an increasing awareness that impulse control disorders (ICDs), including compulsive gambling, buying, sexual behavior, and eating, can occur as a complication of Parkinson’s disease (PD). In addition, other impulsive or compulsive disorders have been reported to occur, including dopamine dysregulation syndrome (DDS) and punding. Case reporting and prospective studies have reported an association between ICDs and the use of dopamine agonists (DAs), particularly at greater dosages, whereas dopamine dysregulation syndrome has been associated with greater dosages of levodopa or short-acting DAs. Data suggest that risk factors for an ICD may include male sex, younger age or younger age at PD onset, a pre-PD history of ICD symptoms, personal or family history of substance abuse or bipolar disorder, and a personality style characterized by impulsiveness. Although psychiatric medications are used clinically in the treatment of ICDs, there is no empiric evidence supporting their use in PD. Therefore, management for clinically significant ICD symptoms should consist of modifications to dopamine replacement therapy, particularly DAs, and there is emerging evidence that such management is associated with an overall improvement in ICD symptomatology. It is important that PD patients be aware that DA 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 cooccurring PD and ICDs.
doi:10.1002/ana.21454
PMCID: PMC3530139  PMID: 19127573
3.  Prevalence of hypersexual behavior in Parkinson’s disease patients: Not restricted to males and dopamine agonist use 
This study investigates the prevalence and demographic characteristics of hypersexuality in Parkinson’s disease (PD). Impulse control disorders in PD patients have been associated with dopamine agonist therapy. Moreover, hypersexuality and pathological gambling have been associated with males, while females may be inherently thought to be more likely to participate in compulsive shopping and binge-eating behaviors. In this study, a screening mail-in survey was sent to all PD patients at a single Movement Disorders Center. One hundred forty one of 400 (35.3%) research packets were returned completed. Fifteen of 141 patients met initial screening criteria for hypersexual behavior. After detailed interview, only 6/141 (4.3%) of PD patients met criteria for pathologic hypersexual behavior. These behaviors included: compulsive masturbation, prostitution, and paraphilias. Patients with a younger age of PD onset were more likely to exhibit hypersexual behavior. Unlike previous report, no significant association was found between hypersexuality and gender or dopamine agonist use. Rather, this study suggests that physicians should be vigilant for hypersexual behavior in all PD patients, regardless of gender and PD medication regimen. Ultimately, given the innate sensitivity of the topic and survey limitations, it is very likely that hypersexual behavior in our cohort, as it is in the general PD population, has been under-reported.
PMCID: PMC2840579  PMID: 20360887
Parkinson’s disease; hypersexuality; impulsive behavior; dopamine agonists
4.  Dopamine Agonist Use is Associated with Impulse Control Disorders in Parkinson’s Disease 
Archives of neurology  2006;63(7):969-973.
Objective
To determine the frequency and correlates of impulse control disorders (ICDs) in Parkinson’s 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 (6.6%) PD patients 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 symptomatology 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
PD patients treated with a dopamine agonist should be made aware of the risk of developing an ICD and monitored clinically. As dopamine agonists are increasing being used for other indications, future research should assess the dopamine agonist-associated risk for ICDs in other populations.
doi:10.1001/archneur.63.7.969
PMCID: PMC1761054  PMID: 16831966
5.  Impulsive choice and response in dopamine agonist-related impulse control behaviors 
Psychopharmacology  2009;207(4):645-659.
Rationale
Dopaminergic medication-related Impulse Control Disorders (ICDs) such as pathological gambling and compulsive shopping have been reported in Parkinson disease (PD).
Hypothesis
We hypothesized that dopamine agonists (DAs) would be associated with greater impulsive choice, or greater discounting of delayed rewards, in PD patients with ICDs (PDI).
Methods
Fourteen PDI patients, 14 PD controls without ICDs and 16 medication-free matched normal controls were tested on (i) the Experiential Discounting Task (EDT), a feedback-based intertemporal choice task, (ii) spatial working memory and (iii) attentional set shifting. The EDT was used to assess impulsivity choice (hyperbolic K-value), reaction time (RT) and decision conflict RT (the RT difference between high conflict and low conflict choices). PDI patients and PD controls were tested on and off DA.
Results
On the EDT, there was a group by medication interaction effect [F(1,26)=5.62; p=0.03] with pairwise analyses demonstrating that DA status was associated with increased impulsive choice in PDI patients (p=0.02) but not in PD controls (p=0.37). PDI patients also had faster RT compared to PD controls F(1,26)=7.51 p=0.01]. DA status was associated with shorter RT [F(3,24)=8.39, p=0.001] and decision conflict RT [F(1,26)=6.16, p=0.02] in PDI patients but not in PD controls. There were no correlations between different measures of impulsivity. PDI patients on DA had greater spatial working memory impairments compared to PD controls on DA (t=2.13, df=26, p=0.04).
Conclusion
Greater impulsive choice, faster RT, faster decision conflict RT and executive dysfunction may contribute to ICDs in PD.
doi:10.1007/s00213-009-1697-y
PMCID: PMC3676926  PMID: 19838863
dopamine agonist; gambling; impulse control; Parkinson disease; delay discounting
6.  Decreased Ventral Striatal Activity with Impulse Control Disorders in Parkinson’s Disease 
Purpose
A range of impulse control disorders (ICDs) are reported to occur in Parkinson’s disease (PD). However, alterations in brain activity at rest and during risk taking occurring with ICDs in PD are not well understood.
Methods
We used both arterial spin labeling (ASL) perfusion fMRI to directly quantify resting cerebral blood flow (CBF) and blood oxygenation level dependent (BOLD) fMRI to measure neural responses to risk taking during performance on the Balloon Analogue Risk Task (BART).
Results
18 PD patients, either with a diagnosis of one or more ICDs (N=9) or no lifetime ICD history (N=9), participated. BOLD fMRI data demonstrated that PD patients without an ICD activate the mesocorticolimbic pathway during risk taking. Compared with non-ICD patients, ICD patients demonstrated significantly diminished BOLD activity in the right ventral striatum during risk taking and significantly reduced resting CBF in the right ventral striatum.
Conclusion
ICDs in PD are associated with reduced right ventral striatal activity at rest and diminished striatal activation during risk taking, suggesting that a common neural mechanism may underlie ICDs in individuals with PD and those without PD. Thus, treatments for ICDs in non-PD patients warrant consideration in PD patients with ICDs.
doi:10.1002/mds.23147
PMCID: PMC3063061  PMID: 20589879
7.  Impulse control disorders in Parkinson’s disease: recent advances 
Current opinion in neurology  2011;24(4):324-330.
Purpose of review
To review the recent advances in the epidemiology and pathophysiology of impulse control disorders (ICD) in Parkinson’s disease (PD).
Recent findings
Large cross-sectional and case-control multicentre studies show that ICDs in PD are common with a frequency of 13.6%. These behaviours are associated with impaired functioning and with depressive, anxiety and obsessive symptoms, novelty seeking and impulsivity. Behavioural subtypes demonstrate differences in novelty seeking and impulsivity suggesting pathophysiological differences. Observational and neurophysiological studies point towards a potential mechanistic overlap between the behavioural (ICDs) and motor (dyskinesias) dopaminergic sequelae. Converging data suggest dopamine agonists in ICDs appear to enhance learning from rewarding outcomes and impulsive choice. ICD patients also have enhanced risk preference and impaired working memory. Neuroimaging data points towards enhanced bottom-up ventral striatal dopamine release to incentive cues, gambling tasks and reward prediction, and possibly inhibition of top-down orbitofrontal influences. Dopamine agonist-related ventral striatal hypoactivity to risk is consistent with impaired risk evaluation.
Summary
Recent large scale studies and converging findings are beginning to provide an understanding of mechanisms underlying ICDs in PD which can guide prevention of these behaviours and optimize therapeutic approaches.
doi:10.1097/WCO.0b013e3283489687
PMCID: PMC3154756  PMID: 21725242
Impulse control disorders; Parkinson’s disease; dopamine agonists; pathological gambling; impulsivity
8.  Impulse control disorders in Parkinson's disease: clinical characteristics and implications 
Neuropsychiatry  2011;1(2):133-147.
SUMMARY
Impulse control disorders (ICDs), specifically those related to excessive gambling, eating, sex and shopping, have been observed in a subset of people with Parkinson's disease (PD). Although some initial case reports claimed that dopamine replacement therapies, particularly dopamine agonists, cause ICDs, more recent, larger and better controlled studies indicate a more complicated picture. While dopamine replacement therapy use is related to ICDs, other vulnerabilities, some related to PD and/or its treatment directly and others seemingly unrelated to PD, have also been associated with ICDs in PD. This suggests a complex etiology with multiple contributing factors. As ICDs occur in a sizable minority of PD patients and can be associated with significant distress and impairment, further investigation is needed to identify factors that can predict who may be more likely to develop ICDs. Clinical implications are discussed and topics for future research are offered.
PMCID: PMC3120055  PMID: 21709778
9.  Patient versus informant reporting of ICD symptoms in Parkinson’s disease using the QUIP: Validity and variability☆ 
Parkinsonism & related disorders  2010;17(3):153-155.
Questions exist regarding the validity of patient-reporting of psychiatric symptoms in Parkinson’s disease (PD). We assessed observer variability and validity in reporting of impulse control disorder (ICD) symptoms in PD by using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease (QUIP). PD patients and their informants (71 pairs) completed the QUIP to assess four ICDs (compulsive gambling, buying, sexual behavior, and eating) in patients. Trained raters then administered a diagnostic interview. Sensitivity of the QUIP for a diagnosed ICD was 100% for both patient- and informant-completed instruments, and specificity was 75% for both raters. Approximately 40% of patients without an ICD diagnosis had a positive QUIP, suggesting that many PD patients experience subsyndromal ICD symptoms that require ongoing monitoring. Agreement between patient- and informant-reporting of any ICD behaviors on the QUIP was moderate (kappa = 0.408), and for individual ICDs was highest for gambling (kappa = 0.550). Overall, a negative QUIP from either the patient or informant rules out the possibility of an ICD, while a positive QUIP requires a follow-up diagnostic interview and ongoing monitoring to determine if symptoms currently are, or in the future become, clinically significant.
doi:10.1016/j.parkreldis.2010.11.015
PMCID: PMC3073062  PMID: 21186135
Impulse control disorders; Parkinson’s disease; QUIP
10.  Prospective Cohort Study of Impulse Control Disorders in Parkinson’s Disease 
Impulse control disorders (ICDs) are potentially serious side effects of dopamine agonist therapy in Parkinson’s disease (PD), but prospective data are lacking about their incidence, time course, and risk factors. This work was a 4-year, prospective cohort study of outpatients with PD and no previous ICDs (N = 164). All subjects treated with a dopamine agonist during the study were followed longitudinally for new-onset ICDs. Baseline characteristics were compared in groups with (ICD+) and without (ICD−) subsequent ICDs. Forty-six subjects were treated with a dopamine agonist, including 25 who were newly treated and 21 who received ongoing dopamine agonist therapy. Of these 46 subjects, 18 (39.1%) developed new-onset ICDs. The timing of ICD onset varied from 3.0 to 114.0 months (median, 23.0) after initiation of dopamine agonist therapy. Baseline demographic characteristics were similar in ICD+ and ICD− groups. At baseline, ICD+ subjects had a greater prevalence of motor complications (61.1% versus 25.0%; P = 0.01) than ICD− subjects, despite comparable total dopaminergic medication usage in both groups (median, 150.0 versus 150.0 levodopa equivalents; P = 0.61). Compared with ICD− subjects, ICD+ subjects had a greater baseline prevalence of caffeine use (100% versus 66.7%; P = 0.007) and higher lifetime prevalence of cigarette smoking (44.4% versus 14.3%; P = 0.04). Peak dopamine agonist doses were higher in ICD+ than ICD− subjects (median 300.0 versus 165.0 L-dopa equivalents; P = 0.03), but cumulative dopamine agonist exposure was similar in both groups. In summary, the timing of new-onset ICDs in PD is highly variable. Risk factors include cigarette smoking, caffeine use, motor complications, and higher peak dopamine agonist dosage.
doi:10.1002/mds.25291
PMCID: PMC3894820  PMID: 23283708
dopamine agonist; dopamine agonist withdrawal syndrome; impulse control disorder; prospective; Parkinson’s disease
11.  Pramipexole-Induced Increased Probabilistic Discounting: Comparison Between a Rodent Model of Parkinson's Disease and Controls 
Neuropsychopharmacology  2012;37(6):1397-1408.
The dopamine agonist pramipexole (PPX) can increase impulsiveness, and PPX therapy for neurological diseases (Parkinson's disease (PD) and restless leg syndrome) is associated with impulse control disorders (ICDs) in subpopulations of treated patients. A commonly reported ICD is pathological gambling of which risk taking is a prominent feature. Probability discounting is a measurable aspect of risk taking. We recently developed a probability discounting paradigm wherein intracranial self-stimulation (ICSS) serves as the positive reinforcer. Here we used this paradigm to determine the effects of PPX on discounting. We included assessments of a rodent model of PD, wherein 6-OHDA was injected into the dorsolateral striatum of both hemispheres, which produced persistent PD-like deficits in posture adjustment. Rats were trained to perform ICSS-mediated probability discounting, in which PD-like and control groups exhibited similar profiles. Rats were treated twice daily for 2 weeks with 2 mg/kg (±)PPX (ie, 1 mg/kg of the active form), a dose that improved lesion-induced motor deficits. In both groups, (±)PPX increased discounting; preference for the large reinforcer was enhanced 30–45% at the most uncertain probabilities. Tolerance did not develop with repeated treatments. Increased discounting subsided within 2 weeks of (±)PPX cessation, and re-exposure to (±)PPX reinstated heightened discounting. Such findings emulate the clinical scenario; therefore, ICSS for discounting assessments in rats exhibited high face validity. This model should prove useful in medication development where assessment of the propensity of a putative therapy to induce risk-taking behaviors is of interest.
doi:10.1038/npp.2011.325
PMCID: PMC3327845  PMID: 22257895
pramipexole; probability discounting; 6-OHDA; gambling; rat; reward; animal models; dopamine; addiction & substance abuse; movement disorders; pramipexole; probability discounting; 6-OHDA; gambling; rat
12.  Dopamine Agonists and Pathologic Behaviors 
Parkinson's Disease  2012;2012:603631.
The dopamine agonists ropinirole and pramipexole exhibit highly specific affinity for the cerebral dopamine D3 receptor. Use of these medications in Parkinson's disease has been complicated by the emergence of pathologic behavioral patterns such as hypersexuality, pathologic gambling, excessive hobbying, and other circumscribed obsessive-compulsive disorders of impulse control in people having no history of such disorders. These behavioral changes typically remit following discontinuation of the medication, further demonstrating a causal relationship. Expression of the D3 receptor is particularly rich within the limbic system, where it plays an important role in modulating the physiologic and emotional experience of novelty, reward, and risk assessment. Converging neuroanatomical, physiological, and behavioral science data suggest the high D3 affinity of these medications as the basis for these behavioral changes. These observations suggest the D3 receptor as a therapeutic target for obsessive-compulsive disorder and substance abuse, and improved understanding of D3 receptor function may aid drug design of future atypical antipsychotics.
doi:10.1155/2012/603631
PMCID: PMC3328150  PMID: 22567537
13.  Long-Term Follow-Up of Impulse Control Disorders in Parkinson’s Disease 
Recent studies have linked dopamine agonist (DA) usage with the development of impulse control disorders (ICDs) in Parkinson’s disease (PD). Little is known about optimal management strategies or the long-term outcomes of affected patients. To report on the clinical interventions and long-term outcomes of PD patients who developed an ICD after DA initiation. Subjects contacted by telephone for a follow-up interview after a mean time period of 29.2 months. They were administered a modified Minnesota Impulse Disorder Interview for compulsive buying, gambling, and sexuality, and also self-rated changes in their ICD symptomatology. Baseline and follow-up dopamine replacement therapy use was recorded and verified by chart review. Of 18 subjects, 15 (83.3%) participated in the follow-up interview. At follow-up, patients were receiving a significantly lower DA levodopa equivalent daily dosage (LEDD) (Z = -3.1, P = 0.002) and a higher daily levodopa dosage (Z = -1.9, P = 0.05), but a similar total LEDD dosage (Z = -0.47, P = 0.64) with no changes in Unified Parkinson’s Disease Rating Scale motor score (Z = -1.3, P = 0.19). As part of ICD management, 12 (80.0%) patients discontinued or significantly decreased DA treatment, all of whom experienced full or partial remission of ICD symptoms by self-report, and 10 (83.3%) of whom no longer met diagnostic criteria for an ICD. For PD patients who develop an ICD in the context of DA treatment, discontinuing or significantly decreasing DA exposure, even when offset by an increase in levodopa treatment, is associated with remission of or significant reduction in ICD behaviors without worsening in motor symptoms.
doi:10.1002/mds.21770
PMCID: PMC2651355  PMID: 17960796
dopamine agonist; gambling; impulse control disorders; Parkinson’s disease
14.  The Functional Anatomy of Impulse Control Disorders 
Impulsive–compulsive disorders such as pathological gambling, hypersexuality, compulsive eating, and shopping are side effects of the dopaminergic therapy for Parkinson’s disease. With a lower prevalence, these disorders also appear in the general population. Research in the last few years has discovered that these pathological behaviors share features similar to those of substance use disorders (SUD), which has led to the term “behavioral addictions”. As in SUDs, the behaviors are marked by a compulsive drive toward and impaired control over the behavior. Furthermore, animal and medication studies, research in the Parkinson’s disease population, and neuroimaging findings indicate a common neurobiology of addictive behaviors. Changes associated with addictions are mainly seen in the dopaminergic system of a mesocorticolimbic circuit, the so-called reward system. Here we outline neurobiological findings regarding behavioral addictions with a focus on dopaminergic systems, relate them to SUD theories, and try to build a tentative concept integrating genetics, neuroimaging, and behavioral results.
doi:10.1007/s11910-013-0386-8
PMCID: PMC3779310  PMID: 23963609
Behavioral addictions; Pathological gambling; Binge eating; Compulsive buying; Hypersexuality; Substance use disorders; Mesocorticolimbic circuit; Reward system; Dopamine; Parkinson; Parkinson’s disease; Neurobiology; Risk factors; Impulse control disorders; Functional anatomy
15.  Dopamine agonists and risk: impulse control disorders in Parkinson's; disease 
Brain  2011;134(5):1438-1446.
Impulse control disorders are common in Parkinson's; disease, occurring in 13.6% of patients. Using a pharmacological manipulation and a novel risk taking task while performing functional magnetic resonance imaging, we investigated the relationship between dopamine agonists and risk taking in patients with Parkinson's; disease with and without impulse control disorders. During functional magnetic resonance imaging, subjects chose between two choices of equal expected value: a ‘Sure’ choice and a ‘Gamble’ choice of moderate risk. To commence each trial, in the ‘Gain’ condition, individuals started at $0 and in the ‘Loss’ condition individuals started at −$50 below the ‘Sure’ amount. The difference between the maximum and minimum outcomes from each gamble (i.e. range) was used as an index of risk (‘Gamble Risk’). Sixteen healthy volunteers were behaviourally tested. Fourteen impulse control disorder (problem gambling or compulsive shopping) and 14 matched Parkinson's; disease controls were tested ON and OFF dopamine agonists. Patients with impulse control disorder made more risky choices in the ‘Gain’ relative to the ‘Loss’ condition along with decreased orbitofrontal cortex and anterior cingulate activity, with the opposite observed in Parkinson's; disease controls. In patients with impulse control disorder, dopamine agonists were associated with enhanced sensitivity to risk along with decreased ventral striatal activity again with the opposite in Parkinson's; disease controls. Patients with impulse control disorder appear to have a bias towards risky choices independent of the effect of loss aversion. Dopamine agonists enhance sensitivity to risk in patients with impulse control disorder possibly by impairing risk evaluation in the striatum. Our results provide a potential explanation of why dopamine agonists may lead to an unconscious bias towards risk in susceptible individuals.
doi:10.1093/brain/awr080
PMCID: PMC3097893  PMID: 21596771
Parkinson's; disease; dopamine; gambling; decision making; risk
16.  Ventral Striatal Dopamine Synthesis Capacity Predicts Financial Extravagance in Parkinson’s Disease 
Impulse control disorders (ICDs), including disordered gambling, can occur in a significant number of patients with Parkinson’s disease (PD) receiving dopaminergic therapy. The neurobiology underlying susceptibility to such problems is unclear, but risk likely results from an interaction between dopaminergic medication and a pre-existing trait vulnerability. Impulse control and addictive disorders form part of a broader psychopathological spectrum of disorders, which share a common underlying genetic vulnerability, referred to as externalizing. The broad externalizing risk factor is a continuously varying trait reflecting vulnerability to various impulse control problems, manifested at the overt level by disinhibitory symptoms and at the personality level by antecedent traits such as impulsivity and novelty/sensation seeking. Trait “disinhibition” is thus a core endophenotype of ICDs, and a key target for neurobiological investigation. The ventral striatal dopamine system has been hypothesized to underlie individual variation in behavioral disinhibition. Here, we examined whether individual differences in ventral striatal dopamine synthesis capacity predicted individual variation in disinhibitory temperament traits in individuals with PD. Eighteen early-stage male PD patients underwent 6-[18F]Fluoro-l-DOPA (FDOPA) positron emission tomography scanning to measure striatal dopamine synthesis capacity, and completed a measure of disinhibited personality. Consistent with our predictions, we found that levels of ventral, but not dorsal, striatal dopamine synthesis capacity predicted disinhibited personality, particularly a propensity for financial extravagance. Our results are consistent with recent preclinical models of vulnerability to behavioral disinhibition and addiction proneness, and provide novel insights into the neurobiology of potential vulnerability to impulse control problems in PD and other disorders.
doi:10.3389/fpsyg.2013.00090
PMCID: PMC3583186  PMID: 23450713
dopa decarboxylase; dopamine; disordered gambling; externalizing; impulse control disorders; impulsivity; reward; ventral striatum
17.  Validation of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease (QUIP) 
Objective
As no comprehensive assessment instrument for impulse control disorders (ICDs) in Parkinson’s disease (PD) exists, the aim of this study was to design and assess the psychometric properties of a self-administered screening questionnaire for ICDs and other compulsive behaviors in PD.
Methods
The Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease (QUIP) has 3 sections: Section 1 assesses four ICDs (involving gambling, sexual, buying, and eating behaviors), Section 2 other compulsive behaviors (punding, hobbyism and walkabout), and Section 3 compulsive medication use. For validation, a convenience sample of 157 PD patients at 4 movement disorders centers first completed the QUIP, and then was administered a diagnostic interview by a trained rater blinded to the QUIP results. A shortened instrument (QUIP-S) was then explored.
Results
The discriminant validity of the QUIP was high for each disorder or behavior (receiver operating characteristic area under the curve [ROC AUC]: gambling=0.95, sexual behavior=0.97, buying=0.87, eating=0.88, punding=0.78, hobbyism=0.93, walkabout=0.79). On post hoc analysis, the QUIP-S ICD section had similar properties (ROC AUC: gambling=0.95, sexual behavior=0.96, buying=0.87, eating=0.88). When disorders/behaviors were combined, the sensitivity of the QUIP and QUIP-S to detect an individual with any disorder was 96% and 94%, respectively.
Conclusions
Scores on the QUIP appear to be valid as a self-assessment screening instrument for a range of ICDs and other compulsive behaviors that occur in PD, and a shortened version may perform as well as the full version. A positive screen should be followed by a comprehensive, clinical interview to determine the range and severity of symptoms, as well as need for clinical management.
doi:10.1002/mds.22571
PMCID: PMC2848971  PMID: 19452562
Parkinson’s disease; impulse control disorders; dopamine dysregulation syndrome; punding; pathological gambling
18.  Dopaminergic and Clinical Correlates of Pathological Gambling in Parkinson’s Disease: A Case Report 
Dopaminergic medication for motor symptoms in Parkinson’s disease (PD) recently has been linked with impulse control disorders, including pathological gambling (PG), which affects up to 8% of patients. PG often is considered a behavioral addiction associated with disinhibition, risky decision-making, and altered striatal dopaminergic neurotransmission. Using [11C]raclopride with positron emission tomography, we assessed dopaminergic neurotransmission during Iowa Gambling Task performance. Here we present data from a single patient with PD and concomitant PG. We noted a marked decrease in [11C]raclopride binding in the left ventral striatum upon gambling, indicating a gambling-induced dopamine release. The results imply that PG in PD is associated with a high dose of dopaminergic medication, pronounced motor symptomatology, young age at disease onset, high propensity for sensation seeking, and risky decision-making. Overall, the findings are consistent with the hypothesis of medication-related PG in PD and underscore the importance of taking clinical variables, such as age and personality, into account when patients with PD are medicated, to reduce the risk of PG.
doi:10.3389/fnbeh.2013.00095
PMCID: PMC3725950  PMID: 23908610
Parkinson’s disease; pathological gambling; impulse control disorders; decision-making; dopamine
19.  Dopamine Agonists and the Suppression of Impulsive Motor Actions in Parkinson’s Disease 
Journal of cognitive neuroscience  2012;24(8):1709-1724.
The suppression of spontaneous motor impulses is an essential facet of cognitive control that is linked to frontal-basal ganglia circuitry. Basal ganglia dysfunction caused by Parkinson’s disease (PD) disrupts the proficiency of action suppression, but how pharmacotherapy for PD impacts impulsive motor control is poorly understood. Dopamine agonists improve motor symptoms of PD, but can also provoke impulsive-compulsive behaviors (ICB). We investigated whether dopamine agonist medication has a beneficial or detrimental effect on impulsive action control in thirty-eight PD patients, half of whom had current ICB. Participants performed the Simon conflict task, which measures susceptibility to acting on spontaneous action impulses as well as the proficiency of suppressing these impulses. Compared to an off agonist state, patients on their agonist were no more susceptible to reacting impulsively, but were less proficient at suppressing the interference from the activation of impulsive actions. Importantly, agonist effects depended on baseline performance in the off agonist state; more proficient suppressors off agonist experienced a reduction in suppression on agonist, whereas less proficient suppressors off agonist showed improved suppression on agonist. Patients with active ICB were actually less susceptible to making fast, impulsive response errors than patients without ICB, suggesting that behavioral problems in this subset of patients may be less related to impulsivity in motor control. Our findings provide further evidence that dopamine agonist medication impacts specific cognitive control processes and that the direction of its effects depends on individual differences in performance off medication.
doi:10.1162/jocn_a_00241
PMCID: PMC3657467  PMID: 22571461
Parkinson’s disease; simon task; inhibition; dopamine agonist; impulse control
20.  Diagnosis and treatment of impulse control disorders in patients with movement disorders 
Impulse control disorders are a psychiatric condition characterized by the failure to resist an impulsive act or behavior that may be harmful to self or others. In movement disorders, impulse control disorders are associated with dopaminergic treatment, notably dopamine agonists (DAs). Impulse control disorders have been studied extensively in Parkinson’s disease, but are also recognized in restless leg syndrome and atypical Parkinsonian syndromes. Epidemiological studies suggest younger age, male sex, greater novelty seeking, impulsivity, depression and premorbid impulse control disorders as the most consistent risk factors. Such patients may warrant special monitoring after starting treatment with a DA. Various individual screening tools are available for people without Parkinson’s disease. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease has been developed specifically for Parkinson’s disease. The best treatment for impulse control disorders is prevention. However, after the development of impulse control disorders, the mainstay intervention is to reduce or discontinue the offending anti-Parkinsonian medication. In refractory cases, other pharmacological interventions are available, including neuroleptics, antiepileptics, amantadine, antiandrogens, lithium and opioid antagonists. Unfortunately, their use is only supported by case reports, small case series or open-label clinical studies. Prospective, controlled studies are warranted. Ongoing investigations include naltrexone and nicotine.
doi:10.1177/1756285613476127
PMCID: PMC3625015  PMID: 23634190
Impulse control disorders; Parkinson’s disease; restless leg syndrome; parkinsonism; dopamine agonist; non-motor complication; neurobehavioural
21.  Frequency of New-Onset Pathologic Compulsive Gambling or Hypersexuality After Drug Treatment of Idiopathic Parkinson Disease 
Mayo Clinic Proceedings  2009;84(4):310-316.
OBJECTIVE: To determine the frequency of new-onset compulsive gambling or hypersexuality among regional patients with Parkinson disease (PD), ascertaining the relationship of these behaviors to PD drug use.
PATIENTS AND METHODS: We retrospectively reviewed the medical records of patients from 7 rural southeastern Minnesota counties who had at least 1 neurology appointment for PD between July 1, 2004, and June 30, 2006. The main outcome measure was compulsive gambling or hypersexuality developing after parkinsonism onset, including the temporal relationship to PD drug use.
RESULTS: Of 267 patients with PD who met the study inclusion criteria, new-onset gambling or hypersexuality was documented in 7 (2.6%). All were among the 66 patients (10.6%) taking a dopamine agonist. Moreover, all 7 (18.4%) were among 38 patients taking therapeutic doses (defined as ≥2 mg of pramipexole or 6 mg of ropinirole daily). Behaviors were clearly pathologic and disabling in 5: 7.6% of all patients taking an agonist and 13.2% of those taking therapeutic doses. Of the 5 patients, 2 had extensive treatment for what was considered a primary psychiatric problem before the agonist connection was recognized.
CONCLUSION: Among the study patients with PD, new-onset compulsive gambling or hypersexuality was documented in 7 (18.4%) of 38 patients taking therapeutic doses of dopamine agonists but was not found among untreated patients, those taking subtherapeutic agonist doses, or those taking carbidopa/levodopa alone. Behaviors abated with discontinuation of agonist therapy or dose reduction. Because this is a retrospective study, cases may have been missed, and hence this study may reflect an underestimation of the true frequency. Physicians who care for patients taking these drugs should recognize the drug's potential to induce pathologic syndromes that sometimes masquerade as primary psychiatric disease.
In patients with Parkinson disease, new-onset compulsive gambling or hypersexuality was documented in 7 of 38 patients taking therapeutic doses of dopamine agonists but was not found among untreated patients, those taking subtherapeutic agonist doses, or those taking carbidopa/levodopa alone.
PMCID: PMC2665974  PMID: 19339647
22.  Epidemiologic and clinical updates on impulse control disorders: a critical review 
The article reviews the current knowledge about the impulse control disorders (ICDs) with specific emphasis on epidemiological and pharmacological advances. In addition to the traditional ICDs present in the DSM-IV—pathological gambling, trichotillomania, kleptomania, pyromania and intermittent explosive disorder—a brief description of the new proposed ICDs—compulsive–impulsive (C–I) Internet usage disorder, C–I sexual behaviors, C–I skin picking and C–I shopping—is provided. Specifically, the article summarizes the phenomenology, epidemiology and comorbidity of the ICDs. Particular attention is paid to the relationship between ICDs and obsessive–compulsive disorder (OCD). Finally, current pharmacological options for treating ICDs are presented and discussed.
doi:10.1007/s00406-006-0668-0
PMCID: PMC1705499  PMID: 16960655
impulse control disorders (ICDs); obsessive–compulsive disorder (OCD); pathological gambling (PG); kleptomania; compulsive–impulsive (C–I) shopping; trichotillomania (TTM); intermittent explosive disorder (IED); C–I Internet usage disorder; C–I sexual behaviors (C–ISBs); C–I skin picking; pyromania
23.  Increased striatal dopamine release in Parkinsonian patients with pathological gambling: a [11C] raclopride PET study 
Brain : a journal of neurology  2009;132(Pt 5):1376-1385.
Pathological gambling is an impulse control disorder reported in association with dopamine agonists used to treat Parkinson’s disease. Although impulse control disorders are conceptualized as lying within the spectrum of addictions, little neurobiological evidence exists to support this belief. Functional imaging studies have consistently demonstrated abnormalities of dopaminergic function in patients with drug addictions, but to date no study has specifically evaluated dopaminergic function in Parkinson’s disease patients with impulse control disorders. We describe results of a [11C] raclopride positron emission tomography (PET) study comparing dopaminergic function during gambling in Parkinson’s disease patients, with and without pathological gambling, following dopamine agonists. Patients with pathological gambling demonstrated greater decreases in binding potential in the ventral striatum during gambling (13.9%) than control patients (8.1%), likely reflecting greater dopaminergic release. Ventral striatal bindings at baseline during control task were also lower in patients with pathological gambling. Although prior imaging studies suggest that abnormality in dopaminergic binding and dopamine release may be markers of vulnerability to addiction, this study presents the first evidence of these phenomena in pathological gambling. The emergence of pathological gambling in a number of Parkinson’s disease patients may provide a model into the pathophysiology of this disorder.
doi:10.1093/brain/awp054
PMCID: PMC3479148  PMID: 19346328 CAMSID: cams2369
Parkinson’s disease; dopamine; impulse control disorders; pathological gambling; PET; functional imaging
24.  Impulse control disorders in Parkinson’s disease: seeking a roadmap toward a better understanding 
Brain Structure & Function  2011;216(4):289-299.
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.
doi:10.1007/s00429-011-0314-0
PMCID: PMC3197927  PMID: 21541715
Imaging; Gambling; Addiction; Impulsive; Compulsive; Dopamine agonist
25.  Binge Eating in Parkinson Disease: Prevalence, Correlates, and the Contribution of Deep Brain Stimulation 
Of 96 Parkinson’s disease (PD) patients at the University of Florida Movement Disorders Center, one (1%) met diagnostic criteria for binge eating disorder (BED). Eight (8.3%) exhibited subthreshold BED. Psychometric criteria classified problem gambling in 17.8%, hoarding in 8.3%, buying in 11.5%, hypersexuality in 1.0%, and mania in 1.0% of patients. More overeaters met psychometric criteria for at least one additional impulse control disorder (67% vs. 29%). No more overeaters than non-overeaters were taking a dopamine agonist (44% vs. 41%). More overeaters had a history of subthalamic DBS (44% vs. 14%). History of DBS was the only independent predictor of overeating.
doi:10.1176/appi.neuropsych.23.1.56
PMCID: PMC3075093  PMID: 21304139
Parkinson’s disease; binge eating; impulse control disorders

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