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Impulse control disorders and dopaminergic treatments in Parkinson's disease
revue neurologique 167 (2011) 827–832
Brief communication
Impulse control disorders and dopaminergic treatments in Parkinson’s disease Les troubles de l’impulsion et les traitements dopaminergiques de la maladie de Parkinson C. Villa, B. Pascual-Sedano, J. Pagonabarraga, J. Kulisevsky * Movement Disorders Unit, Neurology Department, Sant Pau Hospital, Autonomous University of Barcelona, Institut d’Investigacions Biosanita`ries, Sant Pau (IIB-Sant Pau), Centro de Investigacio´n Biome´dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), C/ Mas Casanovas 90, 08025 Barcelona, Spain
article info
abstract
Article history:
A group of disorders sharing a failure to resist an impulse to perform a typically pleasurable
Received 6 September 2010
activity that is finally harmful to the person or to others are known under the common
Accepted 17 January 2011
denomination of impulse control disorders (ICDs). These behaviors, possibly previously
Published on line 18 May 2011
neglected by lack of awareness, are increasingly reported among PD patients. Compelling evidence has stressed the relation between dopaminergic replacement and development of
Keywords:
ICDs in PD, especially but not exclusively, with dopamine agonist therapy. Besides dopa-
Dopaminergic treatments
minergic replacement, younger age, smoking habit, presence of familiar gambling problems
Parkinson’s disease
and alcohol abuse can increase the risk. ICDs in PD may greatly affect patients and
Pathological gambling
caregivers quality of life, stressing the importance of their screening. Management strate-
Hypersexuality
gies include a careful use of dopaminergic therapy using the lowest effective doses. # 2011 Elsevier Masson SAS. All rights reserved.
Eating disorders Buying disorders
r e´ s u m e´ Mots cle´s : The´rapies dopaminergiques
Les maladies ou les de´pendances se traduisant par une impulsion incontroˆlable caracte´rise´e
Maladie de Parkinson
par un besoin impe´rieux de faire une activite´ agre´able sont groupe´s sous le terme de troubles
Jeu pathologique
de l’impulsion. Chez les sujets atteints de la maladie de Parkinson (MP), la fre´quence de ces
Hypersexualite´
comportements longtemps me´connus ou ignore´s serait en augmentation. L’observation
Troubles des conduites alimentaires
clinique est en faveur d’une corre´lation entre le remplacement dopaminergique et le
Achat compulsif
de´veloppement des troubles de l’impulsion chez le parkinsonien, particulie`rement, mais pas exclusivement, apre`s un traitement par agonistes dopaminergiques. Outre le remplacement dopaminergique, le jeune aˆge du patient, le tabagisme, la pre´sence de proble`mes de jeu et l’abus d’alcool sont des facteurs de risque. Les troubles de l’impulsion dans la MP ont un impact important sur la qualite´ de vie du patient et de l’accompagnant, d’ou` l’importance d’un de´pistage. L’utilisation d’une the´rapie dopaminergique minimale fait partie des strate´gies de prise en charge. # 2011 Elsevier Masson SAS. Tous droits re´serve´s.
* Corresponding author. E-mail address : [email protected] (J. Kulisevsky). 0035-3787/$ – see front matter # 2011 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.neurol.2011.01.018
828
1.
revue neurologique 167 (2011) 827–832
Introduction
In the last years the issue of Impulse Control Disorders (ICDs) in patients diagnosed with Parkinson’s disease (PD) have gained interest, particularly due to the possible association with the treatment with dopamine agonists (Dodd et al., 2005; Driver-Dunckley et al., 2003; Molina et al., 2000; Weintraub et al., 2006). Impulse control disorders are defined in the Diagnostic and Statistics Manual of Mental Disorders (DSM-IV, 1994) as group of disorders sharing a failure to resist an impulse to perform a typically pleasurable activity that is finally harmful to the person or to others. It includes pathological gambling, compulsive buying, compulsive sexual behavior, and binge eating. Not rarely, ICDSs can be associated to the development of repetitive obsessive and unproductive behaviors – a compulsive conduct named ‘‘Punding’’ – and to complex addictive behaviors to antiparkinsonian treatment known as dopamine disregulation syndrome (DDS) (Lawrence et al., 2003). Both ICDs and punding, have been related to dopamine replacement therapy (Mamikonyan et al., 2008; Voon et al., 2009), especially with dopamine agonists agents but have also been reported in relation to Levodopa (Molina et al., 2000) use and deep brain stimulation surgery (Lim et al., 2009; Smeding et al., 2007). Data regarding frequency and clinical impact of ICD are relatively recent in the PD literature. Nevertheless, there is increasing consensus that these symptoms occurs in an important proportion of PD patients and may cause an important impairment on the quality of life of both the patient and the caregiver with potentially devastating, social, familial or financial consequences.
2. Demographic data of impulse control disorders (ICDs) in Parkinson’s disease (PD) The prevalence estimated for ICDs in PD patients has been estimated between 2 to 6% for pathological gambling, 2 to 10% for compulsive sexual behaviors, and 0.4 to 2% for compulsive buying (Weintraub, 2008). In a recent multicentric cross-sectional study including more than three thousand PD patients, Weintraub, et al. (Weintraub et al., 2010) reported an overall prevalence of ICDs of 13.6% with 3.9% of patients having two or more ICDs. Specifically, 5.7% of patients suffered compulsive buying, 5% pathological gambling, 4.3% binge eating disorder, and 3.5% compulsive sexual behavior. Most of the patients were men; however there were not important difference in relation to gender. Patients who developed any type of IDCs were younger and unmarried. In this study the presence of smoking habit, antecedents of familiar gambling problems and alcohol abuse were significantly more frequent in patients with a current ICD than patients with no-current ICDs. Hypersexuality was more frequent in men but women had more frequency of compulsive buying and binge eating disorders. (Weintraub et al., 2010).
3. Clinical characteristics of impulse control disorders (ICDs) 3.1.
Pathological gambling
The DSM-IV manual define the diagnostics criteria for pathological/problems gambling, following ten items explaining different behaviors in relation to game (1994) (Table 1). Gambling behavior can include different activities like playing cards for money, betting on horses or dogs or sports games, playing the stock or commodities market, buying lottery tickets, or playing bingo or gambling at a casino, including playing slot machines or gambling at internet. These activities are excessive and preoccupant for the patient and caregiver. (Morasco et al., 2006). A study including 297 PD patients identified ten patients who had problems related to pathological gambling (3.4%). They preferred slot machines and scratch lottery cards, suggesting a behavior related to immediate gratification, lower cognitive resources, and repetitive motor acts. The mean amount of money lost among the ten PD patients owing to pathological gambling was US$10,000 (Voon et al., 2006b). A study comparing PD patients with general medical patients found a 6.1% frequency of gambling among PD patients versus 0.25% in the other group, a risk that accounts for an odds ratio of 25.57 for PD patients of being affected by pathological gambling (OD. 25.57) (Avanzi et al., 2006).
3.2.
Hypersexuality
Hypersexuality is defined as an inappropriate or excessive request of sex from a spouse or a partner, preoccupation whit pornography, telephone sex lines, masturbation or compulsive promiscuity (Voon et al., 2009). Nevertheless, it is difficult to define when an individual’s sexual behavior is without normal limits, as it can be large differences between individuals. The change from normal to hypersexuality is usually based on the comparison between premorbid behavior and that following some kind of intervention like the beginning of dopamine replacement therapy. (Fenu et al., 2009) Frequently after an orgasm the patient do not fell satisfaction and the continuous necessity of performing or thinking in sex may ultimately generate anxiety and frustration. Familiar and social consequences and monetary aspects can be dramatic. Anecdotically, development of zoophilia has been reported after the beginning of bromocriptine in a PD patient (Jimenez-Jimenez et al., 2002). Voon et al. (Voon et al., 2006a) have proposed diagnostic criteria for hypersexuality in PD.
3.3.
Compulsive buying and eating
Other less frequent ICDs described in PD patients are compulsive buying and binge or compulsive eating. Compulsive buying – also called compulsive shopping – has been detected more frequently in women than in men (Weintraub et al., 2010). Patients describe this behavior as an excessive necessity to buy anything, often unnecessary things with severe financial consequences (McElroy et al., 1994).
revue neurologique 167 (2011) 827–832
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Table 1 – Diagnostic criteria for impulse control disorders (ICDs). Les crite`res diagnostiques pour de´sordres de controˆle de l’impulsion. Gambling disorders (DSM-VI definition)
Hypersexuality (Voon et al., 2006)
Compulsive Shopping (McElroy et al., 1994)
Compulsive eating (Binge eating –– DSM IV research diagnostic criteria)
Punding (Evans et al., 2004)
Compulsive medication use (Giovannoni et al., 2000)
Pathological gambling Persistent and current maladaptative gambling behaviour as indicated by five or more of the following Preoccupied about gambling Increasing amount of money spend Repeated unsuccessful attempt to control gambling Restless or irritable when reducing time spend on gambling Means of escape from problems or to relieve dysphoric mood Chasing losses Lies to other about gambling Illegal acts to finance gambling Jeopardised relationship, work or education Relies on other for money Dose not occurs exclusively during period of hypomania or mania Problems gambling Similar to pathological gambling but is indicated by only three to four of the ten criteria The sexual thoughts or behaviour are excessive or an atypical change from baseline indicated by one or more of the fallowing Maladaptive preoccupation whit sexual thoughts Inappropriately or excessive requesting of sex from spouse or partner Habitual promiscuity Use of telephone sexual lines or pornography Paraphilias The behaviour must have persist for at last 1 month The behaviour causes at last one or more of the following Visible distress Attempts to control thought or behaviour unsuccessful or result in marked anxiety or distress Behavior are time-consuming Interferes substantially whit social or occupational functioning The behaviour dose not occurs exclusively during period of hypomania or mania If all criteria exept C are fulfilled the disorder is subsyndromal Maladaptive preoccupation with buying or shopping, whether impulses or behaviour, that Are experienced as irresistible, intrusive, and/or senseless Result in frequent buying of more than can be off order, items that are not needed, or for longer periods of time than intended Causes visible distress, is time-consuming, substantially interferes with social or occupational functioning, or results in financial problems The behaviours do not occur exclusively during periods of hypomania or mania Recurrent binge eating characterised by eating large amounts in a discrete period along with a loss of control Three of more of the following Rapid eating Feeling uncomfortably full Eating large amounts when not hungry Eating alone because of embarrassment of amounts Feeling disgusted or guilty after overeating Visible distress Occurs 2 days per week for 6 months Does not occur with compensatory behaviours or during anorexia or bulimia nervosa An intense fascination with complex, excessive, repetitive, non-goal-oriented behaviours The behaviours include less complex acts such as shuffling papers, reordering bricks, or sorting handbags, or more complex acts such as hobbyism (gardening, painting), writing, or excessive computer use Clinical diagnosis of levodopa-responsive Parkinson’s disease Need for increasing dopamine replacement therapy in excess of that required for motor signs and symptoms Pathological use despite severe behavioural disturbances and drug-induced dyskinesias Social or occupational impairment Development of a dopaminergic withdrawal state with dose reduction
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revue neurologique 167 (2011) 827–832
Binge eating is defined as a compulsive ingest of a large amount of food in a short period of time, and compulsive eating is described as an abnormal ingest of food in excess, during a lot period of time, without necessity to alleviate hunger (1994).
3.4.
Punding behavior
The first description of punding was made in the 1970s by Rylander et al., who described a stereotyped behavior in amphetamine addicts (Rylander, 1972). Punding is a complex stereotyped behavior characterized by an intense fascination with repetitive manipulations of technical equipment, a continual handling, examining, and sorting of common objects, grooming, hoarding, pointless driving or walkabouts, and the engagement in extended monologues devoid of content (Evans et al., 2004). This actions can be simple (e.g., manipulating objects or instruments or sorting of common objects) or complex (e.g., hoarding, gardening, cleaning, singing, writing, or computer use). The type of punding developed can be influenced by the subject´s previous occupation, habits and pastime (Evans et al., 2004; Kulisevsky et al., 2009). Punders may neglect their physiological needs, such as sleep, hunger, and thirst, as well as their social responsibilities. They may or may not retain insight regarding the inappropriateness of their behavior. Interruption of the behaviors leads to irritability and dysphoria with a return to calm when they reassume the activity (Evans et al., 2009). A relationship between punding and DRT has been reported in PD (Evans et al., 2004; Fernandez and Friedman, 1999; Lee et al., 2010) with a positive correlation with the daily dose of levodopa (Lee et al., 2010). The reported prevalence of punding in PD patients ranges between 1.4% and 14%, depending on differences in case ascertainment, medication practices, and clinic population (Voon et al., 2009; Evans et al., 2004). Although it appears mainly related to dopaminergic replacement, appearance of punding has also been reported after deep brain stimulation (Lim et al., 2009). It was suggested that the frequent concurrence of punding with compulsive DRT might represent an important step in the eventual progression to a form of automatic behavior in which voluntary control over drug use is lost (Evans et al., 2004; Lawrence et al., 2003).
3.5.
Dopamine disregulation syndrome
DDS has also been described as hedonistic homoeostatic disregulation, a behavioral disorder associated with substance misuse and addiction (Giovannoni et al., 2000). DDS has been recognized as a consequence of dopamine replacement therapy (DRT) in PD patients, with compulsive use of dopaminergic medications well beyond the dose needed to optimally control motor disability and with patients often fulfilling ICD-10 criteria for ‘‘addiction’’ (Bearn et al., 2004; Evans et al., 2009). Self-injury ideation/behavior and hypomanic behavior may occur during episodes of excessive medication use (Evans et al., 2009).
3.6.
Walkabout
Walkabout has been described in association to DDS. It is defined as excessive, aimless wandering, walking or driving
(Giovannoni et al., 2000). During the on phase, patients with DDS may go on ‘‘walkabout’’ becoming restless and akathisic with an urge to walk or travel. We recently reported the presence of walkabout in five PD patients who exhibited aimless wandering of walking great distances, preferably in the early morning and during ‘‘on’’ state. During their walk, two of them gathered useless objects from the street or in the wastebaskets, and take them home (Pascual-Sedano et al., 2010). Walkabout is considered a compulsive behaviour, and is included in the section 2 of the Questionnaire for Impulsive-Compulsive Disorders in PD (QUIP), besides punding and hobbyism (Weintraub et al., 2009) (see below).
4. Relationship of impulse control disorders (ICDs) to dopamine agonist agents Recent years reports suggested that the emergence of IDCs during treatment with dopamine agonists was a class effect (Avanzi et al., 2006; Voon et al., 2006b; Weintraub et al., 2006) with no clear differences in frequency of ICDs between PD patients treated with pramipexole (17.7%) or ropinirole (15.5%) (Weintraub et al., 2010). In favor, ICDs was also detected in patient’s whit restless legs syndrome treated with dopamine agonist (Abler et al., 2009; Ondo and Lai, 2008) Although, there is a strong class association between dopamine agonist use and all ICDs, treatment with levodopa also appear among other aadditional variables independently associated with ICDs (Abler et al., 2009; Ondo and Lai, 2008). Interestingly, there is an association between higher levodopa dosages, but not dopamine agonist dosages, and ICDs (Abler et al., 2009; Ondo and Lai, 2008). A possible neurobiological explanation for the association between dopamine agonist’s treatment and ICDs might be searched around dopamine-receptor binding profiles. Dopaminergic D3 receptors, abundant in the ventral striatum, has been associated with both behavioral addictions and reward-related processes while D2 and D1 receptors, predominant in the dorsal striatum, mediate the motor effects of dopamine replacement therapies. Second generation non-ergot dopamine agonists (e.g. pramipexole and ropinirole) demonstrate relative selectivity for D3 receptors compared with D2 and D1 receptors (Weintraub, 2008). The ventral tegmental area-nucleus accumbens (VTA-NAc) pathway and other limbic regions that appears implicated in the acute positive emotional effects of natural rewards, such as food, sex, and social interactions, (Breiter et al., 2001; Nestler, 2005) have also been implicated in natural or behavioral addictions (i.e., compulsive consumptions of natural rewards) such as pathological overeating, pathological gambling, and sexual addictions (Fenu et al., 2009). Dopamine has been associated with the reward obtained from the appreciation of beauty and increased sensitivity to sensory stimulus and continuous dopaminergic stimulation represents the main factor that influenced the patient to perceive more emotional aspects of nature, such as light and colors (Kulisevsky et al., 2009).
revue neurologique 167 (2011) 827–832
5.
Diagnostic assessment
Often the patients or their family do not complain spontaneously for the symptoms associated to ICDs, punding or DDS, and they are not aware of the possible relationship between this behavior and the disease or the dopaminergic therapy. Thus, direct questions addressed to the patient about a range of behaviors and an interviewing to the caregiver or informed other is often critical to ensure the detection and assessment of severity of impulsive or compulsive behavioral disorders. Current clinical criteria helping diagnosis for distinct ICDs, such as gambling (1994), hypersexuality (Voon et al., 2006a), compulsive shopping (McElroy et al., 1994), binge/compulsive eating (1994) are available. Proposed criteria for punding (Evans et al., 2004) and DDS (Giovannoni et al., 2000) have also been reported. Weintraub et al. developed a specific scale for screening ICDs, punding and DDS in PD. The QUIP is a brief, selfcompleted screening questionnaire for ICDs and other compulsive behaviors in PD. Using formal diagnostic criteria as the ‘‘gold standard’’ diagnosis, the QUIP has showed good discriminant validity with at least 80% sensitivity and specificity for each of the four ICDs and 96% of sensitivity to detect a subject whit any ICDs or compulsive behavior (Abler et al., 2009; Ondo and Lai, 2008). The Minnesota Impulsive Disorders Interview (MIDI) (Christenson et al., 1994) was developed for use in general population but has been used in PD patients, this scale has items for gambling, compulsive shopping, hypersexuality, binge eating and punding (Isaias et al., 2008; Mamikonyan et al., 2008; Weintraub et al., 2006). Different rating scales like punding questionnaire (Evans et al., 2004), MIDI (Christenson et al., 1994), specific diagnostic criteria for gambling (1994), hipersexuality (Voon et al., 2006a), compulsive buying (McElroy et al., 1994), DDS have been either created or used for the study of ICDs in PD however the only validate scale for use in PD patients is the QUIP.
6.
Conclusions
Compelling evidence has stressed the relation between dopaminergic replacement and development of ICDs in PD, especially with dopamine agonist, whereas greater doses of levodopa may be associate with punding and DDS. A series of major risk factors have also been described for ICDs development in PD such as younger age, smoking habit, presence of familiar gambling problems and alcohol abuse. ICDs in PD may greatly affect quality of life whit serious personal, familial, social and financial consequences, stressing the importance to routinely asking the patients or other informants about their presence. Patients should be educated about possible adverse effect of DRT before start the treatment, specially with a dopamine agonist. Management strategies include a careful use of dopaminergic therapy using the lowest effective doses. The QUIP scale, MIDI and specific diagnostic criteria for the distinct compulsive behaviors could be useful for screening and diagnostic purposes.
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Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. Funding: All authors have no financial disclosures to make.
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Brief communication
Impulse control disorders and dopaminergic treatments in Parkinson’s disease Les troubles de l’impulsion et les traitements dopaminergiques de la maladie de Parkinson C. Villa, B. Pascual-Sedano, J. Pagonabarraga, J. Kulisevsky * Movement Disorders Unit, Neurology Department, Sant Pau Hospital, Autonomous University of Barcelona, Institut d’Investigacions Biosanita`ries, Sant Pau (IIB-Sant Pau), Centro de Investigacio´n Biome´dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), C/ Mas Casanovas 90, 08025 Barcelona, Spain
article info
abstract
Article history:
A group of disorders sharing a failure to resist an impulse to perform a typically pleasurable
Received 6 September 2010
activity that is finally harmful to the person or to others are known under the common
Accepted 17 January 2011
denomination of impulse control disorders (ICDs). These behaviors, possibly previously
Published on line 18 May 2011
neglected by lack of awareness, are increasingly reported among PD patients. Compelling evidence has stressed the relation between dopaminergic replacement and development of
Keywords:
ICDs in PD, especially but not exclusively, with dopamine agonist therapy. Besides dopa-
Dopaminergic treatments
minergic replacement, younger age, smoking habit, presence of familiar gambling problems
Parkinson’s disease
and alcohol abuse can increase the risk. ICDs in PD may greatly affect patients and
Pathological gambling
caregivers quality of life, stressing the importance of their screening. Management strate-
Hypersexuality
gies include a careful use of dopaminergic therapy using the lowest effective doses. # 2011 Elsevier Masson SAS. All rights reserved.
Eating disorders Buying disorders
r e´ s u m e´ Mots cle´s : The´rapies dopaminergiques
Les maladies ou les de´pendances se traduisant par une impulsion incontroˆlable caracte´rise´e
Maladie de Parkinson
par un besoin impe´rieux de faire une activite´ agre´able sont groupe´s sous le terme de troubles
Jeu pathologique
de l’impulsion. Chez les sujets atteints de la maladie de Parkinson (MP), la fre´quence de ces
Hypersexualite´
comportements longtemps me´connus ou ignore´s serait en augmentation. L’observation
Troubles des conduites alimentaires
clinique est en faveur d’une corre´lation entre le remplacement dopaminergique et le
Achat compulsif
de´veloppement des troubles de l’impulsion chez le parkinsonien, particulie`rement, mais pas exclusivement, apre`s un traitement par agonistes dopaminergiques. Outre le remplacement dopaminergique, le jeune aˆge du patient, le tabagisme, la pre´sence de proble`mes de jeu et l’abus d’alcool sont des facteurs de risque. Les troubles de l’impulsion dans la MP ont un impact important sur la qualite´ de vie du patient et de l’accompagnant, d’ou` l’importance d’un de´pistage. L’utilisation d’une the´rapie dopaminergique minimale fait partie des strate´gies de prise en charge. # 2011 Elsevier Masson SAS. Tous droits re´serve´s.
* Corresponding author. E-mail address : [email protected] (J. Kulisevsky). 0035-3787/$ – see front matter # 2011 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.neurol.2011.01.018
828
1.
revue neurologique 167 (2011) 827–832
Introduction
In the last years the issue of Impulse Control Disorders (ICDs) in patients diagnosed with Parkinson’s disease (PD) have gained interest, particularly due to the possible association with the treatment with dopamine agonists (Dodd et al., 2005; Driver-Dunckley et al., 2003; Molina et al., 2000; Weintraub et al., 2006). Impulse control disorders are defined in the Diagnostic and Statistics Manual of Mental Disorders (DSM-IV, 1994) as group of disorders sharing a failure to resist an impulse to perform a typically pleasurable activity that is finally harmful to the person or to others. It includes pathological gambling, compulsive buying, compulsive sexual behavior, and binge eating. Not rarely, ICDSs can be associated to the development of repetitive obsessive and unproductive behaviors – a compulsive conduct named ‘‘Punding’’ – and to complex addictive behaviors to antiparkinsonian treatment known as dopamine disregulation syndrome (DDS) (Lawrence et al., 2003). Both ICDs and punding, have been related to dopamine replacement therapy (Mamikonyan et al., 2008; Voon et al., 2009), especially with dopamine agonists agents but have also been reported in relation to Levodopa (Molina et al., 2000) use and deep brain stimulation surgery (Lim et al., 2009; Smeding et al., 2007). Data regarding frequency and clinical impact of ICD are relatively recent in the PD literature. Nevertheless, there is increasing consensus that these symptoms occurs in an important proportion of PD patients and may cause an important impairment on the quality of life of both the patient and the caregiver with potentially devastating, social, familial or financial consequences.
2. Demographic data of impulse control disorders (ICDs) in Parkinson’s disease (PD) The prevalence estimated for ICDs in PD patients has been estimated between 2 to 6% for pathological gambling, 2 to 10% for compulsive sexual behaviors, and 0.4 to 2% for compulsive buying (Weintraub, 2008). In a recent multicentric cross-sectional study including more than three thousand PD patients, Weintraub, et al. (Weintraub et al., 2010) reported an overall prevalence of ICDs of 13.6% with 3.9% of patients having two or more ICDs. Specifically, 5.7% of patients suffered compulsive buying, 5% pathological gambling, 4.3% binge eating disorder, and 3.5% compulsive sexual behavior. Most of the patients were men; however there were not important difference in relation to gender. Patients who developed any type of IDCs were younger and unmarried. In this study the presence of smoking habit, antecedents of familiar gambling problems and alcohol abuse were significantly more frequent in patients with a current ICD than patients with no-current ICDs. Hypersexuality was more frequent in men but women had more frequency of compulsive buying and binge eating disorders. (Weintraub et al., 2010).
3. Clinical characteristics of impulse control disorders (ICDs) 3.1.
Pathological gambling
The DSM-IV manual define the diagnostics criteria for pathological/problems gambling, following ten items explaining different behaviors in relation to game (1994) (Table 1). Gambling behavior can include different activities like playing cards for money, betting on horses or dogs or sports games, playing the stock or commodities market, buying lottery tickets, or playing bingo or gambling at a casino, including playing slot machines or gambling at internet. These activities are excessive and preoccupant for the patient and caregiver. (Morasco et al., 2006). A study including 297 PD patients identified ten patients who had problems related to pathological gambling (3.4%). They preferred slot machines and scratch lottery cards, suggesting a behavior related to immediate gratification, lower cognitive resources, and repetitive motor acts. The mean amount of money lost among the ten PD patients owing to pathological gambling was US$10,000 (Voon et al., 2006b). A study comparing PD patients with general medical patients found a 6.1% frequency of gambling among PD patients versus 0.25% in the other group, a risk that accounts for an odds ratio of 25.57 for PD patients of being affected by pathological gambling (OD. 25.57) (Avanzi et al., 2006).
3.2.
Hypersexuality
Hypersexuality is defined as an inappropriate or excessive request of sex from a spouse or a partner, preoccupation whit pornography, telephone sex lines, masturbation or compulsive promiscuity (Voon et al., 2009). Nevertheless, it is difficult to define when an individual’s sexual behavior is without normal limits, as it can be large differences between individuals. The change from normal to hypersexuality is usually based on the comparison between premorbid behavior and that following some kind of intervention like the beginning of dopamine replacement therapy. (Fenu et al., 2009) Frequently after an orgasm the patient do not fell satisfaction and the continuous necessity of performing or thinking in sex may ultimately generate anxiety and frustration. Familiar and social consequences and monetary aspects can be dramatic. Anecdotically, development of zoophilia has been reported after the beginning of bromocriptine in a PD patient (Jimenez-Jimenez et al., 2002). Voon et al. (Voon et al., 2006a) have proposed diagnostic criteria for hypersexuality in PD.
3.3.
Compulsive buying and eating
Other less frequent ICDs described in PD patients are compulsive buying and binge or compulsive eating. Compulsive buying – also called compulsive shopping – has been detected more frequently in women than in men (Weintraub et al., 2010). Patients describe this behavior as an excessive necessity to buy anything, often unnecessary things with severe financial consequences (McElroy et al., 1994).
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Table 1 – Diagnostic criteria for impulse control disorders (ICDs). Les crite`res diagnostiques pour de´sordres de controˆle de l’impulsion. Gambling disorders (DSM-VI definition)
Hypersexuality (Voon et al., 2006)
Compulsive Shopping (McElroy et al., 1994)
Compulsive eating (Binge eating –– DSM IV research diagnostic criteria)
Punding (Evans et al., 2004)
Compulsive medication use (Giovannoni et al., 2000)
Pathological gambling Persistent and current maladaptative gambling behaviour as indicated by five or more of the following Preoccupied about gambling Increasing amount of money spend Repeated unsuccessful attempt to control gambling Restless or irritable when reducing time spend on gambling Means of escape from problems or to relieve dysphoric mood Chasing losses Lies to other about gambling Illegal acts to finance gambling Jeopardised relationship, work or education Relies on other for money Dose not occurs exclusively during period of hypomania or mania Problems gambling Similar to pathological gambling but is indicated by only three to four of the ten criteria The sexual thoughts or behaviour are excessive or an atypical change from baseline indicated by one or more of the fallowing Maladaptive preoccupation whit sexual thoughts Inappropriately or excessive requesting of sex from spouse or partner Habitual promiscuity Use of telephone sexual lines or pornography Paraphilias The behaviour must have persist for at last 1 month The behaviour causes at last one or more of the following Visible distress Attempts to control thought or behaviour unsuccessful or result in marked anxiety or distress Behavior are time-consuming Interferes substantially whit social or occupational functioning The behaviour dose not occurs exclusively during period of hypomania or mania If all criteria exept C are fulfilled the disorder is subsyndromal Maladaptive preoccupation with buying or shopping, whether impulses or behaviour, that Are experienced as irresistible, intrusive, and/or senseless Result in frequent buying of more than can be off order, items that are not needed, or for longer periods of time than intended Causes visible distress, is time-consuming, substantially interferes with social or occupational functioning, or results in financial problems The behaviours do not occur exclusively during periods of hypomania or mania Recurrent binge eating characterised by eating large amounts in a discrete period along with a loss of control Three of more of the following Rapid eating Feeling uncomfortably full Eating large amounts when not hungry Eating alone because of embarrassment of amounts Feeling disgusted or guilty after overeating Visible distress Occurs 2 days per week for 6 months Does not occur with compensatory behaviours or during anorexia or bulimia nervosa An intense fascination with complex, excessive, repetitive, non-goal-oriented behaviours The behaviours include less complex acts such as shuffling papers, reordering bricks, or sorting handbags, or more complex acts such as hobbyism (gardening, painting), writing, or excessive computer use Clinical diagnosis of levodopa-responsive Parkinson’s disease Need for increasing dopamine replacement therapy in excess of that required for motor signs and symptoms Pathological use despite severe behavioural disturbances and drug-induced dyskinesias Social or occupational impairment Development of a dopaminergic withdrawal state with dose reduction
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Binge eating is defined as a compulsive ingest of a large amount of food in a short period of time, and compulsive eating is described as an abnormal ingest of food in excess, during a lot period of time, without necessity to alleviate hunger (1994).
3.4.
Punding behavior
The first description of punding was made in the 1970s by Rylander et al., who described a stereotyped behavior in amphetamine addicts (Rylander, 1972). Punding is a complex stereotyped behavior characterized by an intense fascination with repetitive manipulations of technical equipment, a continual handling, examining, and sorting of common objects, grooming, hoarding, pointless driving or walkabouts, and the engagement in extended monologues devoid of content (Evans et al., 2004). This actions can be simple (e.g., manipulating objects or instruments or sorting of common objects) or complex (e.g., hoarding, gardening, cleaning, singing, writing, or computer use). The type of punding developed can be influenced by the subject´s previous occupation, habits and pastime (Evans et al., 2004; Kulisevsky et al., 2009). Punders may neglect their physiological needs, such as sleep, hunger, and thirst, as well as their social responsibilities. They may or may not retain insight regarding the inappropriateness of their behavior. Interruption of the behaviors leads to irritability and dysphoria with a return to calm when they reassume the activity (Evans et al., 2009). A relationship between punding and DRT has been reported in PD (Evans et al., 2004; Fernandez and Friedman, 1999; Lee et al., 2010) with a positive correlation with the daily dose of levodopa (Lee et al., 2010). The reported prevalence of punding in PD patients ranges between 1.4% and 14%, depending on differences in case ascertainment, medication practices, and clinic population (Voon et al., 2009; Evans et al., 2004). Although it appears mainly related to dopaminergic replacement, appearance of punding has also been reported after deep brain stimulation (Lim et al., 2009). It was suggested that the frequent concurrence of punding with compulsive DRT might represent an important step in the eventual progression to a form of automatic behavior in which voluntary control over drug use is lost (Evans et al., 2004; Lawrence et al., 2003).
3.5.
Dopamine disregulation syndrome
DDS has also been described as hedonistic homoeostatic disregulation, a behavioral disorder associated with substance misuse and addiction (Giovannoni et al., 2000). DDS has been recognized as a consequence of dopamine replacement therapy (DRT) in PD patients, with compulsive use of dopaminergic medications well beyond the dose needed to optimally control motor disability and with patients often fulfilling ICD-10 criteria for ‘‘addiction’’ (Bearn et al., 2004; Evans et al., 2009). Self-injury ideation/behavior and hypomanic behavior may occur during episodes of excessive medication use (Evans et al., 2009).
3.6.
Walkabout
Walkabout has been described in association to DDS. It is defined as excessive, aimless wandering, walking or driving
(Giovannoni et al., 2000). During the on phase, patients with DDS may go on ‘‘walkabout’’ becoming restless and akathisic with an urge to walk or travel. We recently reported the presence of walkabout in five PD patients who exhibited aimless wandering of walking great distances, preferably in the early morning and during ‘‘on’’ state. During their walk, two of them gathered useless objects from the street or in the wastebaskets, and take them home (Pascual-Sedano et al., 2010). Walkabout is considered a compulsive behaviour, and is included in the section 2 of the Questionnaire for Impulsive-Compulsive Disorders in PD (QUIP), besides punding and hobbyism (Weintraub et al., 2009) (see below).
4. Relationship of impulse control disorders (ICDs) to dopamine agonist agents Recent years reports suggested that the emergence of IDCs during treatment with dopamine agonists was a class effect (Avanzi et al., 2006; Voon et al., 2006b; Weintraub et al., 2006) with no clear differences in frequency of ICDs between PD patients treated with pramipexole (17.7%) or ropinirole (15.5%) (Weintraub et al., 2010). In favor, ICDs was also detected in patient’s whit restless legs syndrome treated with dopamine agonist (Abler et al., 2009; Ondo and Lai, 2008) Although, there is a strong class association between dopamine agonist use and all ICDs, treatment with levodopa also appear among other aadditional variables independently associated with ICDs (Abler et al., 2009; Ondo and Lai, 2008). Interestingly, there is an association between higher levodopa dosages, but not dopamine agonist dosages, and ICDs (Abler et al., 2009; Ondo and Lai, 2008). A possible neurobiological explanation for the association between dopamine agonist’s treatment and ICDs might be searched around dopamine-receptor binding profiles. Dopaminergic D3 receptors, abundant in the ventral striatum, has been associated with both behavioral addictions and reward-related processes while D2 and D1 receptors, predominant in the dorsal striatum, mediate the motor effects of dopamine replacement therapies. Second generation non-ergot dopamine agonists (e.g. pramipexole and ropinirole) demonstrate relative selectivity for D3 receptors compared with D2 and D1 receptors (Weintraub, 2008). The ventral tegmental area-nucleus accumbens (VTA-NAc) pathway and other limbic regions that appears implicated in the acute positive emotional effects of natural rewards, such as food, sex, and social interactions, (Breiter et al., 2001; Nestler, 2005) have also been implicated in natural or behavioral addictions (i.e., compulsive consumptions of natural rewards) such as pathological overeating, pathological gambling, and sexual addictions (Fenu et al., 2009). Dopamine has been associated with the reward obtained from the appreciation of beauty and increased sensitivity to sensory stimulus and continuous dopaminergic stimulation represents the main factor that influenced the patient to perceive more emotional aspects of nature, such as light and colors (Kulisevsky et al., 2009).
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5.
Diagnostic assessment
Often the patients or their family do not complain spontaneously for the symptoms associated to ICDs, punding or DDS, and they are not aware of the possible relationship between this behavior and the disease or the dopaminergic therapy. Thus, direct questions addressed to the patient about a range of behaviors and an interviewing to the caregiver or informed other is often critical to ensure the detection and assessment of severity of impulsive or compulsive behavioral disorders. Current clinical criteria helping diagnosis for distinct ICDs, such as gambling (1994), hypersexuality (Voon et al., 2006a), compulsive shopping (McElroy et al., 1994), binge/compulsive eating (1994) are available. Proposed criteria for punding (Evans et al., 2004) and DDS (Giovannoni et al., 2000) have also been reported. Weintraub et al. developed a specific scale for screening ICDs, punding and DDS in PD. The QUIP is a brief, selfcompleted screening questionnaire for ICDs and other compulsive behaviors in PD. Using formal diagnostic criteria as the ‘‘gold standard’’ diagnosis, the QUIP has showed good discriminant validity with at least 80% sensitivity and specificity for each of the four ICDs and 96% of sensitivity to detect a subject whit any ICDs or compulsive behavior (Abler et al., 2009; Ondo and Lai, 2008). The Minnesota Impulsive Disorders Interview (MIDI) (Christenson et al., 1994) was developed for use in general population but has been used in PD patients, this scale has items for gambling, compulsive shopping, hypersexuality, binge eating and punding (Isaias et al., 2008; Mamikonyan et al., 2008; Weintraub et al., 2006). Different rating scales like punding questionnaire (Evans et al., 2004), MIDI (Christenson et al., 1994), specific diagnostic criteria for gambling (1994), hipersexuality (Voon et al., 2006a), compulsive buying (McElroy et al., 1994), DDS have been either created or used for the study of ICDs in PD however the only validate scale for use in PD patients is the QUIP.
6.
Conclusions
Compelling evidence has stressed the relation between dopaminergic replacement and development of ICDs in PD, especially with dopamine agonist, whereas greater doses of levodopa may be associate with punding and DDS. A series of major risk factors have also been described for ICDs development in PD such as younger age, smoking habit, presence of familiar gambling problems and alcohol abuse. ICDs in PD may greatly affect quality of life whit serious personal, familial, social and financial consequences, stressing the importance to routinely asking the patients or other informants about their presence. Patients should be educated about possible adverse effect of DRT before start the treatment, specially with a dopamine agonist. Management strategies include a careful use of dopaminergic therapy using the lowest effective doses. The QUIP scale, MIDI and specific diagnostic criteria for the distinct compulsive behaviors could be useful for screening and diagnostic purposes.
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Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. Funding: All authors have no financial disclosures to make.
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