REVIEW
doi:10.1111/j.1360-0443.2010.03218.x
Impulse control disorders in patients with Parkinson’s disease receiving dopamine replacement therapy: evidence and implications for the addictions field add_3218
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Polly Ambermoon1, Adrian Carter1,2, Wayne D. Hall1,3, Nadeeka N. W. Dissanayaka1,4 & John D. O’Sullivan4,5 The University of Queensland, UQ Centre for Clinical Research, Australia,1 The University of Melbourne, School of Psychological Sciences, Australia,2 The University of Queensland, Queensland Brain Institute, Australia,3 Neurology Research Centre, Royal Brisbane Womens’ Hospital, Herston, Australia4 and The University of Queensland, Royal Brisbane Clinical School, School of Medicine, Australia5
ABSTRACT Aims To describe the prevalence, phenomenology and correlates of ‘impulse control disorders’ (ICDs) in patients with Parkinson’s disease (PD) treated with dopamine replacement therapy (DRT); to assess the strength of the evidence that DRT plays a contributory causal role in these disorders; and to highlight the implications of these disorders for research in the addiction field. Methods PubMed and Web of Science databases were searched and the reference lists of papers examined. Results The prevalence of ICDs in Parkinson’s patients using DRT varied between 3.5% and 13.6%, depending on the severity and range of disorders assessed. PD patients with ICDs were: generally younger; had an earlier onset of PD; had a personal or family history of substance abuse or an ICD; and were more likely to be treated with dopamine receptor agonists (DA agonists) than levodopa (l-dopa). There is reasonable evidence that dopaminergic medications play a causal role in ICDs in that they occur at a higher rate in an otherwise low-risk population of adults, begin after initiation of DA agonist therapy and cease upon its discontinuation. A causal relationship is biologically plausible, but the role of other factors (such as concurrent mood disorders) remain to be clarified by better-controlled studies. Conclusions Impulse control disorders among patients with Parkinson’s disease receiving dopamine replacement therapy may provide a unique opportunity for addiction researchers to study the neurobiology of impulsive forms of behaviour (such as problem gambling) that appear to be caused, in part, by the therapeutic use of dopamine receptor agonists. Keywords Behavioural addictions, dopamine agonists, gambling, hypersexuality, impulse control disorders, Parkinson’s disease, substance abuse. Correspondence to: Wayne Hall, Room 708, Building 71/918, UQCCR, The University of Queensland, Royal Brisbane Hospital Site, Herston, 4029, Queensland, Australia. E-mail:
[email protected] Submitted 21 June 2010; initial review completed 16 August 2010; final version accepted 19 September 2010
INTRODUCTION Parkinson’s disease (PD) is a neurodegenerative disorder associated with a loss of dopaminergic neurones in the substantia nigra and ventral tegmental area (VTA) [1]. A reduction of dopamine activity in the dorsal striatum and frontal cortices contributes to significant and progressive motor and non-motor dysfunction, including tremor, stiffness, loss of dexterity, gait and balance disturbance, mood changes, autonomic symptoms and cognitive problems. These symptoms are treated most often with drugs © 2010 The Authors, Addiction © 2010 Society for the Study of Addiction
that compensate for this loss, referred to as dopamine replacement therapy (DRT). They include the dopamine precursor levodopa (l-dopa) and dopamine receptor agonists (DA agonists) such as bromocriptine, cabergoline, pergolide, pramipexole, ropinirole and rotigotine. DRT reduces the Parkinsonian motor and some non-motor impairments, but may be associated with a number of significant side effects such as involuntary movements (dyskinesias) and fluctuations in motor and non-motor symptoms (‘on’ and ‘off’ responses) as the disease progresses [2,3]. These side effects are particularly Addiction
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common with l-dopa, and DA agonists are often used in younger-onset PD patients in an attempt to slow their development [4,5]. In the last decade there have been increasing reports of an association between DRT and impulse control disorders (ICDs) [6,7]. ICDs are defined by ‘a failure to resist an impulse, drive or temptation to perform an act that is harmful to the person or others’ [8]. They include: pathological gambling, compulsive eating, hypersexuality and compulsive shopping. Problem gambling (PG) is the most commonly reported ICD in the general population [9]. It is characterized by a preoccupation with gambling, gambling increasing amounts of money, unsuccessful attempts to control or stop gambling and the persistence of these behaviours despite negative impacts upon relationships, work or education [10]. There are no validated diagnostic criteria for hypersexuality, which is more difficult to assess than problem gambling [9]. Patients typically report increased preoccupation with sexual thoughts, making excessive demands for sex from their partners, increased use of pornography, seeking out prostitutes, engaging in exhibitionism and paraphilia [9]. Compulsive eating involves eating greater amounts of food than necessary to alleviate hunger, often producing harmful weight gain [11]. Compulsive eating may also include binge eating: the impulsive consumption of large quantities of carbohydrate or fat-rich foods in a short period of time. Compulsive buying or shopping can be defined as uncontrollable excessive buying of goods that can lead to psychological distress and substantial debt [12]. There is at present no effective treatment for DRTinduced ICDs other than reducing or changing dopaminergic medication, a pharmacotherapy that is necessary to relieve the debilitating symptoms of PD. A number of pharmacological agents have been tried, including atypical antipsychotics, selective serotonin uptake inhibitors (SSRIs) and naltrexone (an opioid antagonist used in the treatment of alcohol and opioid addiction and trialled in pathological gambling), but the findings have been inconsistent [13]. Given the similarity between DRT-induced behaviours and some behavioural-based addictions, and the role that dopamine may play in both [14,15], addiction researchers may make an important contribution to the diagnosis and treatment of ICDs in PD. The aim of this review is to describe the phenomena of impulse control disorders and to highlight their potential relevance to the addiction field. This review aims to answer the following questions: 1 Which ICDs have been described in PD patients? 2 How common are they? 3 What factors are correlated with their occurrence? 4 Is there sufficient evidence to conclude that DRT is a contributory cause of ICDs? © 2010 The Authors, Addiction © 2010 Society for the Study of Addiction
5 What are the possible implications of these disorders for theories of addiction and addiction research, and for the treatment of ICDs in PD?
MATERIALS AND METHODS A literature search was conducted using the Web of Science and PubMed databases until March 2010. Articles were identified using the following search terms: (Parkinson*, dopamine agonist, l-dopa, DRT, dopamine replacement therap*, pramipexole, ropinirole, pergolide, amantadine, apomorphine, OR bromocriptine) AND (impulse control, gambling, hypersexuality, compulsive, over-eating, binge eating, obesity, intermittent explosive disorder, excessive spending, kleptomania, pyromania, OR trichotillomania). Reference lists were scanned for additional articles. Studies were included if they: (1) were in English; and (2) reported primary research on ICDs in PD patients receiving DRT.
RESULTS Literature search The articles retrieved comprised retrospective, crosssectional and case–control studies. Case–control and cross-sectional studies (see Tables 1 and 2) are discussed in more detail because they provide the strongest evidence on the relationship between DRT use and ICDs, and the best estimates of the prevalence of these disorders and their clinical and other correlates. Data from larger case series were included only for ICD onset and resolution, characteristics not reported routinely in case– control or cross-sectional studies (see [16] for a review of case studies). Nineteen studies met the inclusion criteria, assessing a total of 7336 PD patients. Study characteristics Prevalence data on ICDs were predominately collected via retrospective reviews of medical records. ICD diagnoses were sometimes corroborated by telephone or face-toface clinical interviews. Assessment tools used to identify ICD behaviour varied between studies and assessed various degrees of impulsivity, from small increases in impulsivity to pathological behaviour. Pathological ICD diagnoses were made using standardized instruments such as the South Oaks Gambling Screen (SOGS, with score > 5) for PG or interviews assessing patients against criteria in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) [17]. Other practitioner-constructed screening tools, such as the Minnesota Impulse Disorders Interview (MIDI), were used to assess problematic ICD behaviours (e.g. problem gambling, shopping and Addiction
© 2010 The Authors, Addiction © 2010 Society for the Study of Addiction
Italy (1 Parkinson’s Disease and Movement Disorders Unit of Neurological Division, Hospital of Capri) (tertiary)
Israel (1 tertiary care movement disorders clinic of a university-affiliated municipal hospital) (tertiary)
Canada (1 out-patient tertiary clinic) (tertiary)
Canada (1 university-affiliated movement disorder clinic)
USA (1 Division of Movement Neurology clinic) (tertiary) Italy (NA)
Italy (1 university movement disorders unit)
China (1 hospital)
[36]
[18]
[37]
[31]
[38]
[39]
[23]
PD subjects: Idiopathic PD; DSM-IV pathological gambling, ‘on’ state Controls: age-, gender- and educational level-matched PD patients without an ICD PD subjects: PD on DRT Controls A: spouses of PD patients Controls B: PD patients without an ICD
PD subjects: Idiopathic PD Controls A: healthy, age-matched: randomly selected relatives of hospital employees Controls B: PD patients without an ICD
PD subjects: idiopathic PD Controls A: PD patients without an ICD Controls B: PD patients without PG from previous study PD subjects: clinically diagnosed PD patients Controls A: healthy controls from Canadian population (>45 years old) Controls B: PD patients without an ICD PD subjects: PD Controls: Age- and sex-matched PD patients without PG
PD subjects: PD Controls A: age- and gender-matched healthy controls Controls B: PD patients without an ICD
PD subjects: PD on DRT Controls A: Age- and sex-matched non-PD patients Controls B: Age- and sex-matched PD patients without an ICD
Subjects
Atypical/secondary PD; cognitive abnormality (88 did not return questionnaire)
PD subjects: dementia; antipsychotic or depressant medication; >6 months on DRT; treated with more than one DA agonist Controls: no substance abuse or neurological /psychiatric history No dementia or intellectual decline
History of PG; secondary PD; no responsiveness to l-dopa
Dementia
Dementia; MMSE 65 years; dementia; current substance abuse or psychotic disorder; nneurosurgical treatment for PD (excluded NA) Atypical PD; dementia (DSM-IV diagnosis);
