Parkinsonism and Related Disorders 18S1 (2012) S80S84

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Parkinsonism and Related Disorders

journal homepage: www.elsevier.com/locate/parkreldis

Impulse control disorders in Parkinsons disease

Dolores Vilas, Claustre Pont-Sunyer, Eduardo Tolosa*
Parkinsons Disease and Movement Disorders Unit, Neurology Service, Institut Clnic de Neuroci`encies, Hospital Clnic de Barcelona, Department of Medicine, Universitat de
Barcelona, IDIBAPS, Centro de Investigaci
on Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Catalonia, Spain

article info

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Keywords:
Parkinsons disease
Impulse control disorders
Pathological gambling
Binge eating
Hypersexuality
Dopamine agonists
Compulsive behavior

Impulse control disorders (ICDs), a group of complex behavioral disorders, occur more commonly
in Parkinsons disease (PD) patients than in the general population, with a reported prevalence
up to 13.6% in some studies. The most common ICDs reported are pathological gambling (PG),
hypersexuality (HS), compulsive shopping and compulsive eating. More than a quarter of the
patients with ICDs have 2 or more behavioral addictions. These abnormal behaviors impair
activities of daily living and have a negative impact on quality of life of patients and their
families. As with many other non motor symptoms in PD, ICDs are frequently under-reported by
patients and caregivers and may be under-recognized by the treating physicians. Treatment with
dopamine agonists (DA) is the main risk factor for developing ICDs, and stimulation of mesolimbic
D3 receptors by DA is thought to underlie their development. The DA effect seems to be a class effect
and not specic for any DA. Levodopa can also induce ICDs but much less so than the DAs. The
management of ICDs in PD is complex. Modications in dopaminergic drug treatment are frequently
necessary. In some cases alternative therapies such as atypical antipsychotics, antidepressants or
deep brain stimulation if motor symptoms become incapacitating after adjustment of dopamine
replacement therapy should be considered.
2011 Elsevier Ltd. All rights reserved.

1. Introduction
The term impulse control disorders (ICDs), denes a group of
complex behavioral disorders characterized by failure to resist
an impulse or temptation to perform an act that is harmful
to the individual or to others. ICDs are thought to occur more
commonly in PD patients than in the general population [1]. They
have recently been the focus of considerable interest because
of their association with the use of dopaminergic treatment, in
particular dopamine agonists (DA), also because their presence
has a signicant negative impact on the quality of life of patients
and their families. As with many other non motor symptoms in
PD, ICDs are frequently under-reported by patients and caregivers
and may be under-recognized by the treating physician. Other
neuropsychiatric problems occurring in PD that may be related
to ICD include dopamine dysregulation syndrome, an addictionlike state marked by excessive dopaminergic medication use;
punding, a fascination with meaningless movements or activities
and walkabout, characterized by excessive wandering [2,3].
2. Epidemiology and risk factors
Reported prevalence rates of ICDs in PD vary considerably ranging
from 6% in PD patients not receiving DA and 17% among
* Corresponding author. Eduardo Tolosa. Hospital Clnic de Barcelona,
Universitat de Barcelona, C/Villarroel 170, 08036 Barcelona, Spain.
Tel.: +34 932275785; fax: +34 932275783.
E-mail address: etolosa@clinic.ub.es (E. Tolosa.)
1353-8020/$ see front matter 2011 Elsevier Ltd. All rights reserved.

those on DA treatment [4]. In one study assessing ICDs in

3090 PD patients, the DOMINION (Impulse Control Disorders in
Parkinsons Patients Treated With Pramipexole and Other Agents)
cross-sectional study [5], the 6-month ICD prevalence was 13.6%.
The most common ICDs reported were pathological gambling (PG),
with a prevalence of 5%, hypersexuality (HS) (3.6%), compulsive
shopping (5.7%) and compulsive eating (4.3%). More than a quarter
of the patients with ICDs had 2 or more other behavioral
addictions [5].
DA treatment is the primary risk factor for ICD development in
PD. Several studies support this association [6,7] and it is also
clear from a number of studies and everyday clinical practice
that withdrawal of the offending DA typically results in marked
improvement in the ICD. In the above mentioned DOMINION study
DA treatment was associated with a 2- to 3.5-fold increased odds
of having an ICD. ICDs frequency was similar for pramipexole and
ropinirole (17.7% vs 15.5%), suggesting that the association between
DA and ICDs is a drug class relationship.
Additional variables independently associated with ICDs include
male sex, mainly in HS and PG, younger age [5,8], being unmarried,
current cigarette smoking, prior personal/family history of alcohol
addiction or gambling problems, higher novelty seeking scores
and impulse traits [8], a greater incidence of medication-induced
hypomania/mania [8], an impaired planning [8], levodopa use [5],
and amantadine (PG, HS and buying) [9].
An independent association between levodopa treatment and
ICDs has been found [5]. In patients taking a DA, concurrent

D. Vilas et al. / Parkinsonism and Related Disorders 18S1 (2012) S80S84

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Table 1
Diagnostic criteria for pathological gambling (PG) a
A. Persistent and recurrent maladaptive gambling behavior as indicated by ve or more of the following:
1.

Is preoccupied with gambling (eg preoccupied with reliving past gambling experiences, handicapping or planning the next venture, or thinking of
ways to get money with which to gamble)

2.

Needs to gamble with increasing amounts of money in order to achieve the desired excitement

3.

Has repeated unsuccessful efforts to control, cut back or stop gambling

4.

Is restless or irritable when attempting to cut down or stop gambling

5.

Gambles as a way of escaping from problems or of relieving a dysphoric mood (e.g., feelings of helplessness, guilt, anxiety, depression)

6.

After losing money gambling, often returns another day to get even (chasing ones losses)

7.

Lies to family members, therapist or others to conceal the extent of involvement with gambling

8.

Has committed illegal acts such as forgery, fraud, theft, or embezzlement to nance gambling

9.

Has jeopardized or lost a signicant relationship, job, or educational or career opportunity because of gambling

10. Relies on others to provide money to relieve a desperate nancial situation caused by gambling
B. The gambling behavior is not better accounted for by a manic episode
a

American Psychiatric Association, American Psychiatric Association Task Force on DSM-IV [11]. Diagnostic and statistical manual of mental disorders:
DSM-IV-TR. 4th ed. Washington, DC: American Psychiatric Association; 2000.

levodopa use increased the odds of an ICD by approximately 50%.

While the relation between ICDs and DA therapy is not dose-related,
in the case of levodopa only high dosages were also associated with
ICDs [5].
3. Clinical manifestations
ICDs are under-recognized in clinical practice. Most patients do
not spontaneously offer information about ICD behaviors, either
because of shame or because they do not understand that it is
related to PD and its treatment. Most common ICDs in PD are PG, HS,
compulsive shopping and compulsive eating. Early detection of ICDs
is crucial and all patients should be questioned directly about such
behavior. A useful tool to detect ICDs can be the Questionnaire
for Impulsive-Compulsive Disorders I Parkinsons Disease (QUIPCurrent-Short), a validated quick screening questionnaire that when
positive should be followed by a clinical directed interview [10].
Pathological gambling (PG): PG is dened as an inability to resist
gambling impulses despite severe repercussion on personal, family
or professional life. PG is persistent and recurrent maladaptive
gambling with tolerance or withdrawal, maladaptive behaviors
and consequences (risking signicant relationships or employment,
turning to others for nancial assistance) (Table 1). The more
frequent PG modes are slot machines, lottery scratch cards and
bingo. PG occurs more frequently during the on period [12].
Cultural differences are thought to have a signicant impact on
prevalence rates and in Far Eastern countries PG prevalence is
higher than in Asia [13]. Voon et al. [8] studied the factors
associated with dopaminergic drug-related PG in PD. When
compared with patients without, those with PG had younger age of
onset, higher novelty seeking, a greater incidence of medicationinduced hypomania/mania, an impaired planning and personal/
family history of alcohol use disorders.
Hypersexual behavior (HS): HS typically entails an increase in
premorbid sexual activities as well as an increase in the variety
of sexual behaviors. In patients with HS the need for sexual
behavior consumes so much money, time, concentration and energy
that the patient describes himself as out of control. Intrusive
unwanted paraphiliac thoughts prevent concentration on other
life demands and are the source of anxiety. Orgasm does not
produce satiety in the way it typically does for age mates [14].
HS occurs predominantly in males with relatively early-onset PD,
patients with prior history of tobacco or alcohol addiction, and
can be associated to other inappropriate behavior or psychotic

symptoms [9,14]. HS is associated to treatment with DA alone

(including apomorphine) or adjunctive to levodopa, selegiline and
amantadine [9] although this last relation is controversial, as
discussed below.
Compulsive shopping: This is dened as a maladaptive
preoccupation with buying or shopping, or maladaptive buying or
shopping impulses, frequent buying of more than can be afforded,
items that are not needed, or shopping for longer periods of time
than intended. The buying impulses cause marked distress, are
time-consuming, interfere signicantly with social or occupational
functioning or result in nancial problems [15].
Compulsive eating: Most frequent clinical presentations are an
increase in the food intake dramatically in the setting of new-onset
food cravings for carbohydrates, sweets, and/or salty foods; a newonset binge eating, compulsively eating both larger portions of food
at mealtimes and more frequent snacks throughout the day and
tendency to compulsively snack or binge in the middle of the night.
The consequence of this is an unintentional and undesired increase
in the weight and body mass index [16]. Compulsive shopping and
binge eating are more common in female PD patients whereas
compulsive sexual behaviors have been more frequently reported
in males [4,5] (Table 2).
Other symptoms associated with ICDs: Other neuropsychological disturbances such as novelty seeking and impulsivity have been
associated with ICDs in PD. Their presence may vary depending
on ICD type. Pathological gambling and compulsive shopping, for
example, share similarities in higher novelty seeking and impulsive
choice as compared with hypersexuality and binge eating. In
another study, high scores in depression, anxiety and obsessivecompulsive symptoms have been reported in ICD PD patients [18].
Motor uctuations are more common in patients with ICDs, and
early and severe dyskinesias (within the rst 1224 months) have
been considered a warning sign for the development of dopamine
dysregulation syndrome or ICDs [13].
4. Pathophysiology of ICDs
A role for dopaminergic stimulation in the development of ICDs
has been conrmed by several lines of evidence. Underlying
pathological changes occurring in PD probably do not play a
major role since ICDs are known to occur in other conditions
treated with DA such as restless legs syndrome [19]. While
dopaminergic mechanisms are important, not all patients taking
dopaminergic drugs develop these behaviors and ICDs probably

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D. Vilas et al. / Parkinsonism and Related Disorders 18S1 (2012) S80S84

Table 2
Proposed criteria for compulsive buying and pathological hypersexuality
Proposed criteria for compulsive buying a
A.

Maladaptive preoccupation with buying or shopping, or maladaptive buying or shopping impulses or behavior, as indicated by at least one of the following:
1. Frequent preoccupation with buying or impulses to buy that is/are experienced as irresistible, intrusive and/or senseless
2. Frequent buying of more than can be afforded, frequent buying of items that are not needed, or shopping for longer periods of time than intended

B.

The buying preoccupations, impulses, or behaviors cause marked distress, are time-consuming, signicantly
interfere with social or occupational functioning or result in nancial problems (eg, indebtedness or bankruptcy)

C.

The excessive buying or shopping behavior does not occur exclusively during periods of hypomania or mania

Proposed diagnostic criteria for pathological hypersexuality b

A

The sexual thoughts or behaviors are excessive or an atypical change from baseline marked by one or more of the following:
1. Maladaptive preoccupation with sexual thoughts
2. Inappropriately or excessively requesting sex from spouse or partner
3. Habitual promiscuity
4. Compulsive masturbation
5. Telephone sex lines or pornography
6. Paraphilias

B.

The behavior must have persisted for at least one month

C.

The behavior causes at least one of the following:

1. Marked distress
2. Attempts to control thoughts or behavior are unsuccessful or result in marked anxiety or distress
3. Are time consuming
4. Interfere signicantly with social or occupational functioning

D. The behavior does not occur exclusively during periods of hypomania or mania
E.
a
b

If all criteria except C are fullled, the disorder is subsyndromal

McElroy SL, Keck Jr PE, Pope Jr HG, Smith JM, Strakowski SM [17]. Compulsive buying: a report of 20 cases. J Clin Psychiatry 1994;55:2428.
Voon V, Hassan K, Zurowski M, de Souza M, Thomsen T, Fox S, et al. [4] Prevalence of repetitive and reward-seeking behaviors in Parkinson disease. Neurology
2006;67:12547.

arise from a complex interaction between pharmacologic and nonpharmacologic predisposing factors like young age, male sex and
certain personality traits [20].
It has been hypothesized that treating the motor symptoms
associated to the dorsal motor striatal dopaminergic deciency,
may result in an overdose in the cognitive and limbic pathways
of the ventral corticostriatal circuitry resulting in ICDs [20]. These
central dopaminergic pathways (mesolimbic and mesocortical) are
intricately linked to the brains reward system and are implicated
in various states of addiction. Activation of these systems is
thought to be mediated by stimulation of D3 receptors which are
predominantly expressed in ventral striatum and mediate reward,
emotional and cognitive processes. Non-ergot DA currently used
in PD has a high afnity for the D2/D3 receptors compared to
D1 receptors.
Several functional imaging studies strengthen the links between
the ICDs in PD and addiction in general, where abnormalities of
the reward pathways including the ventral striatum, the cingulate
gyrus and the orbitofrontal cortex. Steeves et al. [21] for example,
have described results of a [11 C]raclopride positron emission
tomography (PET) study assessing dopaminergic function during
gambling in PD patients. Patients with PG demonstrated greater
decreases in binding potential in the ventral striatum during
gambling than controls, likely reecting greater dopaminergic
release. Findings are similar to those reported in subjects with
chemical addictions.
The presences of ICDs in some patients receiving low doses of
dopaminergic drugs suggests that a genetic predisposition may

play a role in some cases, and genetic polymorphisms have been

reported as possible contributors to ICD susceptibility in PD. Such
genetic polymorphisms include the D3 dopamine receptor p.S9G
and GRIN2B c.366C>G [22]. Recently, a variant of the serotonin 2A
receptor gene (HTR2A) has been reported to be associated with ICDs
in PD patients receiving dopamine replacement therapy, mainly
those taking low doses of dopaminergic drugs [23]. For a review
of potential mechanisms involved in ICDs in PD see recent reviews
by Voon et al. and Djamshidian et al. [13,20].
5. Management of ICDs in PD
Minimizing the risk of developing ICDs through preventive
strategies is an important rst step. ICDs, analogous to dyskinesias,
once fully developed can be difcult to manage. Accordingly, before
starting or modifying dopaminergic treatment potential risk factors
such as male sex, young age and a history of drug abuse should be
taken into consideration.
The management of ICDs in PD is complex and there are
limited data to support any particular therapeutic strategy for
the management of ICDs in PD. It is rst important to identify
subjects with ICDs. Brief screening tests may be employed. It is
also important to involve the spouse or other family members in
the management of ICDs and a psychiatric consultation may be
indicated.
The association of dopamine replacement therapy and ICDs
suggests that modications in dopaminergic treatment may be
an effective strategy. Several reports, and everyday practice in

D. Vilas et al. / Parkinsonism and Related Disorders 18S1 (2012) S80S84

the clinic, have documented improvement or ICDs resolution

with discontinuation of DA therapy, reduction of DA dose or
switching to a different DA [6,7]. Still long-term outcomes are
not fully known, only one study suggests that reducing the
dose of dopamine agonists is associated with improvement in
ICD symptoms over time in PD patients [24]. The effectiveness of
changing agonists is not entirely clear. Furthermore some patients
do not experience remission of ICD symptoms with these strategies,
suggesting a multifactorial etiology in some cases. In these cases
long-acting dopaminergic drugs instead of short-acting ones have
been suggested since they provide more continuous stimulation of
DA receptors which may involve less risk than rapid, intermittent
or pulsatile stimulation. There is no proof though that such strategy
is effective.
When tapering DA medications a stereotyped withdrawal
syndrome (DAWS) that can lead to profound disability can
occur in a subset of patients. Physicians should monitor patients
closely. The symptoms of DAWS resemble those of other
drug withdrawal syndromes and include anxiety, panic attacks,
dysphoria, diaphoresis, fatigue, pain, orthostatic hypotension, and
drug cravings. In a retrospective cohort study of 93 non-demented
patients with PD, 19% developed DAWS. All subjects with DAWS had
baseline DA-related ICDs [25].
When these recommendations fail, the clinical management of
ICDs patients can be complicated. Atypical antipsychotics, antidepressants, mood stabilizers and various psychosocial interventions
have been recommended [6,9]. The role of these various agents in
the management of ICDs is not well established as the data are
primarily case reports [13].
A recent controlled study of 17 PD patients suggested that
amantadine may be efcacious for the treatment of PG in patients
with PD [26]. Amantadine 200 mg/day abolished or reduced PG in
all patients. However, in the DOMINION study amantadine use was
associated with the presence of 1 or more ICDs and at an individual
ICD level this association was observed for compulsive gambling,
sexual behavior, and shopping [5]. This association also was present
in multivariable analysis after controlling for possible confounding
clinical variables, including DA use and levodopa dosage.
Zonisamide (ZNS) has also been evaluated in PD patients
with ICDs in an open non-randomized trial [27]. There was a
marked reduction in the severity of impulsive behaviors and
global impulsiveness and the drug was generally well tolerated.
Adequately designed studies are needed to conrm these results.
In addition to pharmacological treatment, psychosocial interventions also may have a role in the management of ICDs. Counseling
and limiting access to money and medications in conjunction with
alterations in dopaminergic treatment have beneted some patients
but long-term follow-up data are needed.
The efcacy of subthalamic nucleus (STN) stimulation for
ICDs in PD has not been fully claried. Published reports are
contradictory. Some case series suggest that deep brain stimulation
(DBS) of STN could improve ICDs by decreasing levodopa dose or
discontinuation of DA [28]. However, caution should be emphasized
as symptoms may worsen in the early postoperative period
associated with hypomania/mania, and new-onset postoperative PG
has been reported [29]. ICDs should not be considered an indication
for DBS.
6. Conclusions
ICDs are not uncommon neuropsychiatric disturbances in PD with
a reported prevalence of up to 13.6% in some studies. These
abnormal behaviors impair activities of daily living and have a
negative impact on quality of life of patients and their families.
Treatment with DAs is the main risk factor for developing ICDs.
Stimulation of mesolimbic D3 receptors by DA is thought to underlie

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the development of these disorders. The DA effect seems to be a

class effect and not specic for any particular DA. Levodopa can also
induce ICDs but much less so than DAs. The management of ICDs in
PD is complex. On the base of the documented association between
dopaminergic treatments and ICDs, modications in dopaminergic
drug treatment are frequently necessary. Emerging data suggest
that reducing the dose of dopamine agonists is associated
with improvement in ICD symptoms over time in PD patients.
Other possible approaches to altering dopamine replacement
therapies in PD patients with ICDs include discontinuing or
switching dopamine agonist therapies, reducing levodopa dose, and
considering alternative therapies such as atypical antipsychotics or
deep brain stimulation if motor symptoms become incapacitating
after alteration of dopamine replacement therapy.
Conict of interests
Eduardo Tolosa has received honoraria for lectures from Boehringer
Ingelheim, Novartis, UCB, GSK, Solvay, Teva and Lundbeck and
participated in advisory boards for Boehringer Ingelheim, Novartis,
Teva and Solvay. Dolores Vila and Claustre Pont declare no conicts
of interest.
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