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1.  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
2.  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
3.  The Risky Business of Dopamine Agonists in Parkinson Disease and Impulse Control Disorders 
Behavioral neuroscience  2011;125(4):492-500.
Risk-taking behavior is characterized by pursuit of reward in spite of potential negative consequences. Dopamine neurotransmission along the mesocorticolimbic pathway is a potential modulator of risk behavior. In patients with Parkinson's Disease (PD), impulse control disorder (ICD) can result from dopaminergic medication use, particularly Dopamine Agonists (DAA). Behaviors associated with ICD include hypersexuality as well as compulsive gambling, shopping, and eating, and are potentially linked to alterations to risk processing. Using the Balloon Analogue Risk task, we assessed the role of agonist therapy on risk-taking behavior in PD patients with (n=22) and without (n=19) active ICD symptoms. Patients performed the task both ‘on’ and ‘off’ DAA. DAA increased risk-taking in PD patients with active ICD symptoms, but did not affect risk behavior of PD controls. DAA dose was also important in explaining risk behavior. Both groups similarly reduced their risk-taking in high compared to low risk conditions and following the occurrence of a negative consequence, suggesting that ICD patients do not necessarily differ in their ability to process and adjust to some aspects of negative consequences. Our findings suggest dopaminergic augmentation of risk-taking behavior as a potential contributing mechanism for the emergence of ICD in PD patients.
doi:10.1037/a0023795
PMCID: PMC3144294  PMID: 21604834
Impulse Control Disorders; Dopamine Agonists; Parkinson Disease; Risk behavior
4.  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
5.  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
6.  Impulse control disorders in Parkinson's disease 
Since the original descriptions of hedonistic homeostatic dysregulation syndrome and pathological gambling in Parkinson's disease, impulse control disorders, such as compulsive spending, punding, or binge eating, are increasingly recognized. Although the term hedonistic homeostatic dysregulation syndrome has been supplanted by the concept of the dopamine dysregulation syndrome, the features of severe dyskinesias, cyclical mood disorder with hypomania or manic psychosis, and impairment of social and occupational functioning in the setting of increased intake of antiparkinson therapy remain. At this time, impulse control disorder is defined as maladaptive behaviors that emerge with disease progression and increasing antiparkinson medications. These behaviors may be disruptive, such as punding, or destructive, such as compulsive spending, gambling, binge eating, or hypersexuality.
doi:10.3410/M1-29
PMCID: PMC2924724  PMID: 20948752
7.  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
8.  Dopamine-Induced Nonmotor Symptoms of Parkinson's Disease 
Parkinson's Disease  2011;2011:485063.
Nonmotor symptoms of Parkinson's disease (PD) may emerge secondary to the underlying pathogenesis of the disease, while others are recognized side effects of treatment. Inevitably, there is an overlap as the disease advances and patients require higher dosages and more complex medical regimens. The non-motor symptoms that emerge secondary to dopaminergic therapy encompass several domains, including neuropsychiatric, autonomic, and sleep. These are detailed in the paper. Neuropsychiatric complications include hallucinations and psychosis. In addition, compulsive behaviors, such as pathological gambling, hypersexuality, shopping, binge eating, and punding, have been shown to have a clear association with dopaminergic medications. Dopamine dysregulation syndrome (DDS) is a compulsive behavior that is typically viewed through the lens of addiction, with patients needing escalating dosages of dopamine replacement therapy. Treatment side effects on the autonomic system include nausea, orthostatic hypotension, and constipation. Sleep disturbances include fragmented sleep, nighttime sleep problems, daytime sleepiness, and sleep attacks. Recognizing the non-motor symptoms that can arise specifically from dopamine therapy is useful to help optimize treatment regimens for this complex disease.
doi:10.4061/2011/485063
PMCID: PMC3096061  PMID: 21603184
9.  Should Hypersexual Disorder be Classified as an Addiction? 
Sexual addiction & compulsivity  2013;20(1-2):10.1080/10720162.2013.768132.
Hypersexual behavior has been documented within clinical and research settings over the past decade. Despite recent research on hypersexuality and its associated features, many questions remain how best to define and classify hypersexual behavior. Proposed diagnostic criteria for Hypersexual Disorder (HD) have been proposed for the DSM-5 and a preliminary field trial has lent some support to the reliability and validity of the HD diagnosis. However, debate exists with respect to the extent to which the disorder might be categorized as a non-substance or behavioral addiction. In this article, we will discuss this debate in the context of data citing similarities and differences between hypersexual disorder, drug addictions, and pathological gambling. The authors of this paper conclude that despite many similarities between the features of hypersexual behavior and substance-related disorders, the research on HD at this time is in its infancy and much remains to be learned before definitively characterizing HD as an addiction at this time.
doi:10.1080/10720162.2013.768132
PMCID: PMC3836191  PMID: 24273404
sex; hypersexual disorder; behavioral addictions; gambling; substance abuse
10.  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
11.  The four As associated with pathological Parkinson disease gamblers: anxiety, anger, age, and agonists 
Several studies have related pathological gambling in PD to dopamine agonist therapy. A mail-in survey was sent to PD patients seen at the University of Florida Movement Disorders Center to determine gambling frequency and behavior, and any lifestyle or environmental factors associated with compulsive gambling in PD. 462 surveys were sent and 127 completed surveys were returned, of which ten were from patients who met criteria for compulsive gambling. All ten were taking dopamine agonists coincident with the compulsive gambling. Compulsive gamblers were younger, and psychological distress measures revealed that compulsive gamblers exhibited higher levels of anxiety, anger, and confusion. Thus in this cohort, we have uncovered the several characteristics of the most likely PD compulsive gambler, namely: (young) age, “angry”, “anxious”, and using a (dopamine) agonist.
PMCID: PMC2654528  PMID: 19300546
Parkinson; gambling; compulsive behavior; dopamine agonist; anxiety
12.  Dopamine Modulates Reward System Activity During Subconscious Processing of Sexual Stimuli 
Neuropsychopharmacology  2012;37(7):1729-1737.
Dopaminergic medication influences conscious processing of rewarding stimuli, and is associated with impulsive–compulsive behaviors, such as hypersexuality. Previous studies have shown that subconscious subliminal presentation of sexual stimuli activates brain areas known to be part of the ‘reward system'. In this study, it was hypothesized that dopamine modulates activation in key areas of the reward system, such as the nucleus accumbens, during subconscious processing of sexual stimuli. Young healthy males (n=53) were randomly assigned to two experimental groups or a control group, and were administered a dopamine antagonist (haloperidol), a dopamine agonist (levodopa), or placebo. Brain activation was assessed during a backward-masking task with subliminally presented sexual stimuli. Results showed that levodopa significantly enhanced the activation in the nucleus accumbens and dorsal anterior cingulate when subliminal sexual stimuli were shown, whereas haloperidol decreased activations in those areas. Dopamine thus enhances activations in regions thought to regulate ‘wanting' in response to potentially rewarding sexual stimuli that are not consciously perceived. This running start of the reward system might explain the pull of rewards in individuals with compulsive reward-seeking behaviors such as hypersexuality and patients who receive dopaminergic medication.
doi:10.1038/npp.2012.19
PMCID: PMC3358742  PMID: 22395731
dopamine; backward masking; sexual motivation; functional imaging; reward system; dopamine; sexual behavior/related disorders; neuropharmacology; imaging; clinical or preclinical; reward system; backward masking; nucleus accumbens
13.  Hypersexual Behavior in Frontotemporal Dementia: A Comparison with Early-Onset Alzheimer’s Disease 
Archives of sexual behavior  2013;42(3):501-509.
The basis of hypersexual behavior among patients with dementia is not entirely clear. Hypersexual behavior may be a particular feature of behavioral variant frontotemporal dementia (bvFTD), which affects ventromedial frontal and adjacent anterior temporal regions specialized in interpersonal behavior. Recent efforts to define Hypersexual Disorder indicate an increasing awareness of heightened sexual activity as a source of personal distress and functional impairment, and clarification of hypersexuality in bvFTD could contribute to understanding the neurobiology of this behavior. This study reviewed 47 patients with bvFTD compared to 58 patients with Alzheimer’s disease (AD) for the presence of heightened sexual activity to the point of distress to caregivers and others. Hypersexual behavior occurred in 6 (13%) bvFTD patients compared to none of the AD patients. Caregivers judged all six bvFTD patients with hypersexual behavior as having a dramatic increase in sexual frequency from premorbid levels. All had general disinhibition, poor impulse control, and actively sought sexual stimulation. They had widened sexual interests and experienced sexual arousal from previously unexciting stimuli. One patient, with early and predominant right anterior temporal involvement, was easily aroused by slight stimuli, such as touching her palms. Although previously considered to be predominantly disinhibited sexual behavior as part of generalized disinhibition, these patients with dementia illustrate varying degrees of increased sexual desire. We conclude that bvFTD is uniquely associated with hypersexuality; it is more than just cognitive impairment with frontal disinhibition but also involves alterations in sexual drive, possibly from right anterior temporal-limbic involvement in this disease.
doi:10.1007/s10508-012-0042-4
PMCID: PMC3596488  PMID: 23297146
hypersexuality; dementia; right temporal lobe; frontotemporal dementia
14.  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
15.  Management of sexual dysfunction in Parkinson’s disease 
Nonmotor symptoms, among them sexual dysfunction, are common and underrecognized in patients with Parkinson disease; they play a major role in the deterioration of quality of life of patients and their partners. Loss of desire and dissatisfaction with their sexual life is encountered in both genders. Hypersexuality (HS), erectile dysfunction and problems with ejaculation are found in male patients, and loss of lubrication and involuntary urination during sex are found in female patients. Tremor, hypomimia, muscle rigidity, bradykinesia, ‘clumsiness’ in fine motor control, dyskinesias, hypersalivation and sweating may interfere with sexual function. Optimal dopaminergic treatment should facilitate sexual encounters of the couple. Appropriate counselling diminishes some of the problems (reluctance to engage in sex, problems with ejaculation, lubrication and urinary incontinence). Treatment of erectile dysfunction with sildenafil and apomorphine is evidence based. HS or compulsive sexual behaviour are side effects of dopaminergic therapy, particularly by dopaminergic agonists, and should be treated primarily by diminishing their dose. Neurologists should actively investigate sexual dysfunction in their Parkinsonian patients and offer treatment, optimally within a multidisciplinary team, where a dedicated professional would deal with sexual counselling.
doi:10.1177/1756285611411504
PMCID: PMC3229252  PMID: 22164191
Parkinson’s disease; sexual dysfunction; erectile dysfunction; desire; orgasm; hypersexuality; management; sexual counseling
16.  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
17.  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
18.  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
19.  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
20.  The depressive façade in a case of compulsive sex behavior with frottage 
Indian Journal of Psychiatry  2013;55(2):183-185.
Compulsive sexual behavior consists of sexual obsessions and compulsions that are recurrent, distressing, and interfere with daily functioning. It has been called hypersexual disorder in the upcoming diagnostic and statistical manual 5th edition. Though hypersexuality is commonly seen in mania, it can also be seen in depression and anxiety disorders. This case report describes a case that presented with depression and had underlying compulsive sexual behavior in the form of frottage.
doi:10.4103/0019-5545.111460
PMCID: PMC3696245  PMID: 23825856
Compulsive sexual behavior; depression; frottage; frotteurism; hypersexuality; sexual addiction
21.  Decision-making, impulsivity and addictions: Do Parkinson’s disease patients jump to conclusions? 
Links between impulsive compulsive behaviors in treated Parkinson’s disease, behavioral addictions and substance abuse have been postulated, but no direct comparisons have been carried out so far.
We directly compared patients with Parkinson’s disease with and without impulsive compulsive behaviors with illicit drug abusers, pathological gamblers and age-matched healthy controls using the beads task, a test of reflection impulsivity and a working memory task.
We found that all patients with Parkinson’s disease made more impulsive and irrational choices than the control group. Parkinson’s disease patients who had an impulsive compulsive behavior showed similar behavior to illicit substance abusers whereas patients without impulsive compulsive behaviors more closely resembled pathological gamblers. In contrast we found no difference in working memory performance within the Parkinson’s disease groups. However Parkinson’s disease patients without impulsive compulsive behaviors remembered distractors significantly less than all other patients during working memory tests.
We were able to correctly classify 96% of the Parkinson’s disease patients with respect to whether or not they had an impulsive compulsive behavior by analyzing 3 trials of the 80/20 loss condition of the beads task with a negative prediction value of 92.3% and we propose that this task may prove to be a powerful screening tool to detect an impulsive compulsive behavior in Parkinson’s disease. Our results also suggest that intact cortical processing and less distractibility in Parkinson’s disease patients without impulsive compulsive behaviors may protect them from developing behavioral addictions.
doi:10.1002/mds.25105
PMCID: PMC3412901  PMID: 22821557
Impulsive compulsive behavior; Parkinson’s disease; reflection impulsivity; pathological gambling; substance abuse; beads task
22.  Frequency of impulse control behaviours associated with dopaminergic therapy in restless legs syndrome 
BMC Neurology  2011;11:117.
Background
Low doses of dopamine agonists (DA) and levodopa are effective in the treatment of restless legs syndrome (RLS). A range of impulse control and compulsive behaviours (ICBs) have been reported following the use of DAs and levodopa in patients with Parkinson's disease. With this study we sought to assess the cross-sectional prevalence of impulse control behaviours (ICBs) in restless legs syndrome (RLS) and to determine factors associated with ICBs in a population cohort in Germany.
Methods
Several questionnaires based on validated and previously used instruments for assessment of ICBs were mailed out to patients being treated for RLS. Final diagnoses of ICBs were based on stringent diagnostic criteria after psychiatric interviews were performed.
Results
10/140 RLS patients of a clinical cohort (7.1%) were finally diagnosed with ICBs, 8 of 10 on dopamine agonist (DA) therapy, 2 of 10 on levodopa. 8 of the 10 affected patients showed more than one type of abnormal behaviour. Among those who responded to the questionnaires 6/140 [4.3%] revealed binge eating, 5/140 [3.6%] compulsive shopping, 3/140 [2.1%] pathological gambling, 3/140 [2.1%] punding, and 2/140 [1.4%] hypersexuality in psychiatric assessments. Among those who did not respond to questionnaires, 32 were randomly selected and interviewed: only 1 patient showed positive criteria of ICBs with compulsive shopping and binge eating. ICBs were associated with higher DA dose (p = 0.001), younger RLS onset (p = 0.04), history of experimental drug use (p = 0.002), female gender (p = 0.04) and a family history of gambling disorders (p = 0.02), which accounted for 52% of the risk variance.
Conclusion
RLS patients treated with dopaminergic agents and dopamine agonists in particular, should be forewarned of potential side effects. A careful history of risk factors should be taken.
doi:10.1186/1471-2377-11-117
PMCID: PMC3195705  PMID: 21955669
Restless legs syndrome; impulse control disorders; dopamine agonist; gambling; levodopa
23.  Mechanisms underlying dopamine-mediated reward bias in compulsive behaviors 
Neuron  2010;65(1):135.
Summary
Pathological behaviors such as problem gambling or shopping are characterized by compulsive choice despite alternative options and negative costs. Reinforcement learning algorithms allow a computation of prediction error, a comparison of actual and expected outcomes, which updates our predictions and influence our subsequent choices. Using a reinforcement learning model, we show data consistent with the idea that dopamine agonists in susceptible individuals with Parkinson's disease increase the rate of learning from gain outcomes. Dopamine agonists also increase striatal prediction error activity thus signifying a “better than expected” outcome. Thus, our findings are consistent with a model whereby a distorted estimation of the gain cue underpins a choice bias towards gains.
doi:10.1016/j.neuron.2009.12.027
PMCID: PMC2822730  PMID: 20152119
24.  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
25.  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

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