Impulse control disorders and depression in Finnish patients with Parkinson's disease

IntroductionImpulse control disorders occur frequently in patients with Parkinson's disease. However, the frequencies have been investigated mainly in patients from secondary or tertiary care centers, and thus, the prevalence rates in general community are not known.ObjectiveOur objective was to study the prevalence rates of impulse control disorders and related factors in a large, non-selected sample of Parkinson's disease patients.MethodsWe conducted a cross-sectional survey among Parkinson's disease patients from Finnish Parkinson Association [n = 575; 365 men, 240 women, median age 64 (range 43–90) years]. Problem and pathological gambling were estimated with the South Oaks Gambling Screen, risk for impulse control disorders with the validated Questionnaire for Impulsive–Compulsive Disorders in Parkinson's Disease, and depression with the Beck Depression Inventory.ResultsThe frequency of pathological gambling was 7.0%. The overall frequency of a positive screen for an impulse control disorder was 34.8%, and 12.5% of the patients screened positive for multiple disorders. Depressive symptoms were statistically the most important factor in explaining variance in impulse control disorder risk, even more than sex, age, age of disease onset, alcohol use, or medication.ConclusionsThe high proportion of patients screened positive for impulse control disorders in a non-selected sample emphasize the importance of routine screening of these disorders in Parkinson's disease. Pathological gambling prevalence in Parkinson's disease is seven times higher than in the general population in Finland. The results underline the importance of depression in impulse control disorders associated with Parkinson's disease.     

Pathological gambling in Parkinson's disease. A comprehensive review

Pathological gambling (PG) and other Impulse Control Disorders (ICDs), such as hypersexuality, compulsive eating and buying, are often reported in Parkinson's disease (PD). The prevalence of PG is 2.2%–7% in treated PD patients, which is higher than the background population rate. As other non motor symptoms in PD, PG is frequently under-reported by patients and caregivers and may be under-recognized by the treating physicians.Factors associated with PG include male sex, younger age or younger age at PD onset, personal or family history of substance abuse or ICD, a personality profile characterized by impulsiveness, and treatment with dopamine agonists (DA) more than with levodopa (l-dopa). The DA effect seems to be a class effect and not specific for any DA.Neurofunctional studies suggest that medication-induced downregulation of frontostriatal connections and upregulation of striatum might combine to induce impulsive behavior. A dysfunction of fronto-subcortical circuits in PD patients with PG is also supported by neuropsychological findings of impaired executive control and monitoring abilities.Management of ICDs in PD is complex, and until now only discontinuation and/or tapering of DA treatment seem to be an effective management strategy for ICDs in PD. There is no empirical evidence supporting the use of psychiatric drugs for PG such as antipsychotics and antidepressants. Data regarding the effect of deep brain stimulation (DBS), particularly of subthalamic nucleus, on PG and ICDs in PD are still limited and sometimes conflicting since improvement of PG or new onset of PG after surgery have been reported.     

Concomitant development of hypersexuality and delusional jealousy in patients with Parkinson's disease: A case series

BackgroundBoth impulse-control disorders and delusional jealousy (DJ) may be considered non-motor side-effects of dopamine agonist therapy in Parkinson's disease (PD). We aimed to investigate the possible concomitant development of these features in PD and their clinical correlates.MethodsWe performed a cross-sectional investigation in 1063 consecutive PD patients with the Questionnaire for Impulsive Compulsive Disorders in Parkinson's disease and the Parkinson's Psychosis Questionnaire.Results81 patients presented ICDs (prevalence 7.61%) and 23 patients presented DJ (17 males, 6 females; prevalence 2.16%). 9 male PD patients presented both DJ and ICDs (39.13% of patients with DJ, 11.11% of patients with ICDs; prevalence of 0.84% in the whole PD sample), with a concomitant onset of delusional jealousy and hypersexuality in 8 cases and a concomitant onset of delusional jealousy and pathological gambling in 2 cases.DiscussionHypersexuality and delusional jealousy may occur independently in PD patients “on” dopamine agonist therapy, but may develop together probably reflecting a common alteration of sexuality (sexual arousal and jealousy) The presence of both of these clinical features and sexuality more in general should be investigated when features of either one of them appear. Further confirmation is needed in larger samples of patients.     

Pathological gambling in Parkinson's disease—a review of the literature

The prevalence of pathological gambling is 3.4% to 6% in treated Parkinson's disease, which is higher than the background population rate. In this review we discuss current evidence to indicate that dopamine agonists are much more likely to trigger this behavior than either L ‐dopa or selective monoamine oxidase B inhibitor monotherapy. New insights from recent behavioral and functional imaging studies and possible treatment approaches are also covered. A PubMed literature search using the terms “gambling” and “Parkinson's disease,” “impulse control disorder,” “impulsive compulsive behaviour,” “dopamine agonist,” of individual dopamine agonists, and of ongoing drug trials, using http://www.clinicaltrials.gov , was carried out for the period up to January 2011. © 2011 Movement Disorder Society     

Impulse control disorders and related behaviours (ICD-RBs) in Parkinson's disease patients: Assessment using “Questionnaire for impulsive-compulsive disorders in Parkinson's disease” (QUIP)

Background:There is limited data on the prevalence of impulse control disorder and related behaviors (ICD-RBs) in Indian patients with Parkinson''s Disease (PD). In the context of potential genetic and environmental factors affecting the expression of ICD-RBs, studying other multiethnic populations may bring in-sights into the mechanisms of these disorders.Objectives:To ascertain point prevalence estimate of ICD-RBs in Indian PD patients, using the validated “Questionnaire for Impulsive-Compulsive Disorders in Parkinson''s disease (QUIP)” and to examine their association with Dopamine replacement therapy (DRT).Results:Total of 299 patients participated in the study. At least one ICD-RB was present in 128 (42.8%), at least one Impulse control disorder (ICD) was present in 74 (24.75%) and at least one Impulse control related compulsive behaviour (ICRB) was present in 93 (31.1%) patients. Punding was the most frequent (12.4%) followed by hyper sexuality (11.04%), compulsive hobbyism (9.4%), compulsive shopping (8.4%), compulsive medication use (7.7%), compulsive eating (5.35%), walkabout (4%) and pathological gambling (3.3%). ≥ 2 ICD-RBs were observed in 15.7% of patients. After multivariate analysis, younger age of onset, being unmarried were specifically associated with presence of ICD. Longer disease duration was specifically associated with presence of ICRB. Whereas smoking and higher dopamine levodopa equivalent daily doses (DA LEDD) were associated with both presence of ICD and ICRB. Higher LD LEDD was specifically associated with presence of ICD-RB.Conclusions:Our study revealed a relatively higher frequency of ICD-RBs, probably because of the use of screening instrument and because we combined both ICDs and ICRBs. Also high proportion of DA use (81.6%) among our patients might be responsible. The role of genetic factors that might increase the risk of developing ICD-RBs in this population needs further exploration.     

Impulse control disorders in Parkinson's disease patients with RLS: a cross sectional-study

BackgroundAlthough dopamine replacement therapy is the main risk factor for the occurrence of Impulse Control Disorders (ICDs) in Parkinson's disease (PD), non-pharmacological risk factors for have also been identified in that population and sleep disorders could be part of them. Our objective is to determine whether Restless Legs Syndrome (RLS), that has been associated with more impulsive choices in general population regardless of dopaminergic therapy, could be associated with a specific psycho-behavioral profile and ICDs in PD.MethodsEighty consecutive PD patients were screened for the presence of RLS in a cross-sectional study. Sleep features were evaluated during one video-polysomnography. The frequency of ICDs, according to standard criteria, together with a broad range of psycho-behavioral features using the Ardouin Scale of Behavior in PD, were compared in patients with RLS (PD-RLS, n = 30) versus without RLS (PD-nRLS, n = 50).ResultsPD patients with RLS reported significantly more ICDs than those without RLS (50% versus 26%, p = 0.03), especially compulsive eating disorders, and a different psycho-behavioral profile with more hyperdopaminergic behaviors. There was no between group difference for total and dopamine agonists levodopa equivalent doses. However, age and durations of both disease and dopaminergic treatment were greater in the RLS group. Multivariate and propensity score analyses controlling for age, gender, total sleep time, disease severity, dose and duration of treatment, anxiety and depression showed that RLS was an independent predictor of ICDs in PD (OR = 5.91 [1.63; 22.1] and OR = 2.89 [1.63; 6.67] respectively).ConclusionRLS per se could be a risk factor for impulsive behaviors in PD.     

Motor and non-motor features of Parkinson's disease that predict persistent drug-induced Parkinsonism

BackgroundDrug-induced Parkinsonism is common, causes significant morbidity, and can be clinically indistinguishable from idiopathic Parkinson's disease. Additionally, drug-induced Parkinsonism may, in some cases, represent “unmasking” of incipient Parkinson's disease. Clinical features or tests that distinguish degenerative from pharmacologic Parkinsonism are needed.MethodsWe performed a retrospective case-control study of 97 drug-induced Parkinsonism subjects and 97 age-matched patients with Parkinson's disease. We compared the frequency of subjective motor and non-motor complaints, objective motor findings (Unified Parkinson's Disease Rating Scale Part III) and, where available, objective olfactory tests. We also performed a nested case-control study wherein we compared these same features between drug-induced Parkinsonism patients based on whether or not they recovered after changing the offending agent.ResultsNon-motor symptoms including constipation and sexual dysfunction were more common in Parkinson's disease than in drug-induced Parkinsonism. While total motor scores were similar between groups, Postural Instability-Gait Difficulty scores were also higher in Parkinson's disease. Features that were significantly different or showed a trend towards significance in both comparisons included subjective loss of facial expression, dream-enactment behavior, autonomic complaints and Postural Instability-Gait Difficulty scores. Hyposmia was more common in Parkinson's disease and was strongly predictive of persistent drug-induced Parkinsonism after therapy change (odds ratio 30.3, 95% confidence interval: 1.5–500, p = 0.03).ConclusionsA constellation of motor and non-motor features may differentiate unmasked Parkinson's disease from drug-induced Parkinsonism. In particular, olfactory testing may offer a simple and inexpensive method to help predict outcomes in drug-induced Parkinsonism and, potentially, identify a cohort of pre-motor Parkinson's disease.     

Impulsive and compulsive behaviors among Danish patients with Parkinson's disease: Prevalence,depression, and personality

IntroductionDopaminergic medication administered to ameliorate motor symptoms of Parkinson's disease is associated with impulse control disorders, such as pathological gambling, hypersexuality, compulsive buying, and binge eating. Studies indicate a prevalence of impulse control disorders in Parkinson's disease of 6–16%.ObjectiveTo estimate the prevalence of impulsive and compulsive behaviors among Danish patients with Parkinson's disease and to explore the relation of such behavioral disorders to depression and personality.Methods490 patients with Parkinson's disease (303 males), identified through the National Danish Patient Registry, were evaluated with: 1) the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease; 2) the Geriatric Depression Scale; and 3) the NEO-Personality Inventory.Results176 (35.9%) patients reported impulsive and compulsive behaviors sometime during Parkinson's disease (current symptoms in 73, 14.9%). Hereof, 114 (23.3%) reported multiple behavioral symptoms. Patients with behavioral symptoms were significantly younger, were younger at PD onset, had longer disease duration, displayed more motor symptoms, and received higher doses of dopaminergic medication than patients without behavioral symptoms. Furthermore, they reported significantly more depressive symptoms and scored significantly higher on neuroticism and lower on both agreeableness and conscientiousness than patients without behavioral symptoms.ConclusionA history of impulsive and compulsive behaviors are common in Danish patients with Parkinson's disease and have clinical correlates that may allow identification of patients at risk for developing these behaviors.     

Past smoking and current dopamine agonist use show an independent and dose-dependent association with impulse control disorders in Parkinson's disease

BackgroundPrevious studies have described the association between dopamine replacement therapy in Parkinson's disease and impulse control disorders.MethodsA case–control study was performed to establish the prevalence of four of these behaviors in Brazilian patients with Parkinson's disease on stable dopamine replacement therapy and the possible associated risk factors. We investigated 152 patients and 212 healthy controls for pathological gambling, compulsive sexual behavior and compulsive buying and eating.ResultsOverall, patients had more impulsive control disorders than controls (18.4% vs. 4.2%, P < 0.001). Impulse control disorders were more common in younger patients (P = 0.008) and in those taking dopamine agonist (P < 0.001) and levodopa (P = 0.02). Higher Unified Parkinson's Disease Rating Scale motor score (P = 0.03) and past smoking (P = 0.02) were also associated in the univariate analysis. Variables independently associated with impulse control disorders were history of smoking (odds ratio = 1.059 for each year of smoking, P = 0.010) and current use of pramipexole (odds ratio = 2.551 for each increase in 1 mg, P < 0.001).ConclusionsDopaminergic stimulation and previous exposure to smoking are independently associated with impulse control disorders in a dose-dependent manner.     

Intertemporal choice in Parkinson's disease

The administration of dopamine agonists in Parkinson's disease has been associated with impulse control disorders, in particular, pathological gambling. In the present investigation, 17 patients with Parkinson's disease without impulse control disorders and 17 matched control participants were offered choices between monetary rewards (ranging between 11 and 80 euros) available immediately and larger rewards (between 25 and 85 euros) available after delays ranging from 7 to 186 days. Participants had a 1‐in‐6 chance of winning a reward that they chose on 1 randomly selected trial. Assuming a hyperbolic discounting model, k values were estimated from the pattern of participants' choices. Patients were tested twice, once on dopamine agonist medication and once after 12 hours without medication. Patients showed a considerably steeper discounting function than healthy controls independent of medication status, with k values more than 3 times larger than those of controls. This study shows that patients with Parkinson's disease without clinically apparent impulse control disorders nevertheless tend to make impulsive decisions in intertemporal monetary choice. The lack of difference between sessions could be a result either of the persistent effects of dopaminergic therapy or hint at a genuine medication‐independent change in intertemporal choice behavior in Parkinson's disease. This needs to be addressed in further studies. The paradigm used is easy to apply and should be used more extensively to describe decision behavior in Parkinson's disease. © 2011 Movement Disorder Society     

Impulse control disorders are associated with lower ventral striatum dopamine D3 receptor availability in Parkinson's disease: A [11C]-PHNO PET study

IntroductionReduced postsynaptic D3 dopaminergic receptor availability has been reported in the ventral striatum of pathological gamblers without Parkinson's disease (PD) and in patients with PD and impulse control disorders (ICD). However, a direct relationship between ventral striatum D3 dopaminergic receptors and the severity of ICD in PD patients has not yet been proven using a validated tool for ICD in PD, such as the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease-Rating Scale (QUIP-RS). In this pilot study, we investigated the relationship between ventral striatum D3 dopamine receptor availability and severity of impulse control disorder (ICD) in Parkinson's disease (PD).MethodsTwelve patients were assessed with PET and the high affinity dopamine D3 receptor radioligand [¹¹C]-PHNO. Severity of ICD was assessed with the QUIP-RS.ResultsWe found that lower ventral striatum D3 receptor availability measured with [¹¹C]-PHNO PET was associated with greater severity of ICD, as measured by the QUIP-RS score (rho = −0.625, p = 0.03).ConclusionThese findings suggest that the occurrence and severity of ICD in Parkinson's disease may be linked to reductions in ventral striatum dopamine D3 receptor availability. Further studies in larger cohort of patients need to be performed in order to confirm our findings and clarify whether lower ventral striatum D3 receptor may reflect a pharmacological downregulation to higher dopamine release in ventral striatum of patients with ICD or a patients' predisposition to ICD.     

Scales to assess impulsive and compulsive behaviors in Parkinson's disease: Critique and recommendations

Impulse control disorders (ICDs) and related impulsive and compulsive behaviors (together called ICBs) have been increasingly recognized in the context of Parkinson's disease (PD) and treatment. The International Parkinson's and Movement Disorder Society commissioned a task force to assess available clinical screening instruments and rating scales, including their clinimetric properties, make recommendations regarding their utility, and suggest future directions in scale development and validation. The literature was systematically searched for scales measuring a range of reported ICBs in PD. A scale was designated “recommended” if the scale had been employed in PD studies, been used beyond the group that developed it, and had adequate clinimetric data published for PD. Numerous diagnostic screening tools and severity rating scales were identified for a range of ICBs, including compulsive medication use, punding/hobbyism, walkabout, pathological gambling, hypersexuality, compulsive or binge eating, compulsive buying, reckless driving, compulsive exercise, pyromania, trichotillomania, hoarding, kleptomania, intermittent explosive disorder, and internet addiction. For screening across the range of ICBs (except compulsive medication use), the Questionnaire for Impulsive‐Compulsive Disorders in Parkinson's disease (QUIP) and QUIP‐Rating Scale (QUIP‐RS) are recommended, and for severity rating across the range of ICBs the QUIP‐RS and the Ardouin Scale of Behavior in Parkinson's Disease are recommended. The Scale for Outcomes in Parkinson's Disease–Psychiatric Complications is recommended for rating of hypersexuality and the compulsive behaviors gambling/shopping. Further testing of established scales against gold standard diagnostic criteria is urgently required for all other individual ICBs in PD. © 2019 International Parkinson and Movement Disorder Society © 2019 International Parkinson and Movement Disorder Society     

Addictive behaviors and Parkinson's disease

IntroductionIn Parkinson's disease, the degeneration of the dopaminergic system and the longstanding exposure to dopamine replacement therapy (DRT) may cause, in a group of vulnerable patients, dysregulation of the brain reward system.State of the artsThese patients develop DRT-related compulsions, which include addiction to levodopa or dopamine dysregulation syndrome (DDS), punding, and impulse control disorders (ICDs). ICDs or behavioral addiction reported in Parkinson's disease include pathological gambling, hypersexuality, compulsive buying and binge eating. Although the underlying pathophysiology is still poorly understood, these behaviors are linked by their reward-based and repetitive nature. Such behaviors may result in devastating psychosocial impairment for the patients and are often hidden.Perspective and conclusionsThe recognition of these behaviors is important and allows a better clinical management. Although the limited data do not permit particular therapeutic strategies, some approaches are worth considering: DRT reduction, trials of non-dopaminergic medications and subthalamic chronic stimulation.     

Differentiating drug-induced parkinsonism from Parkinson's disease: An update on non-motor symptoms and investigations

Drug-induced parkinsonism is the second most common cause of parkinsonism after Parkinson's disease and their distinction has crucial implications in terms of management and prognosis. However, differentiating between these conditions can be challenging on a clinical ground, especially in the early stages. We therefore performed a review to ascertain whether assessment of non-motor symptoms, or use of ancillary investigations, namely dopamine transporter imaging, transcranial sonography of the substantia nigra, and scintigraphy for myocardial sympathetic innervation, can be recommended to distinguish between these conditions.Among non-motor symptoms, there is evidence that hyposmia can differentiate between patients with “pure” drug-induced parkinsonism and those with degenerative parkinsonism unmasked by an anti-dopaminergic drug. However, several issues, including smoking history and cognitive functions, can influence smell function assessment. Higher diagnostic accuracy has been demonstrated for dopamine transporter imaging. Finally, preliminary evidence exists for sympathetic cardiac scintigraphy to predict dopaminergic pathway abnormalities and to differentiate between drug-induced parkinsonism and Parkinson's disease.Imaging of the dopaminergic pathway seems to be the only, reasonably available, technique to aid the differential diagnosis between drug-induced parkinsonism and Parkinson's disease.     

Severe multivalvular heart disease: A new complication of the ergot derivative dopamine agonists

We report on 4 new cases of valvular heart disease in Parkinson's disease patients treated with the ergot derivative dopamine agonists pergolide and cabergoline. Noninflammatory fibrotic degeneration of cardiac valves has been reported to occur in patients with carcinoid syndrome and to occasionally complicate therapies with the anti‐migraine ergot alkaloid ergotamine and methysergide and with the appetite suppressants fenfluramine and dexfenfluramine. In these cases, the pathogenesis is suspected to involve serotonin‐mediated abnormal fibrogenesis by means of the 5‐HT2B receptors, which are expressed in the fibroblasts of heart valves. Based on strikingly similar echocardiographic and histopathological features, we strongly suspect that ergot‐derived dopamine agonists may cause a valvular heart disease nearly identical to that seen in those conditions. These cases add to a rapidly growing and worrying list of similar published reports, suggesting that we may well be facing a novel, yet unrecognized, complication of this class of agents, which are widely used not only in Parkinson's disease but also in restless legs syndrome and various common endocrine dysfunctions. Therefore, until more is known about the true prevalence of this side effect, we propose that an assessment of cardiac function be performed before and in the course of a long‐term therapy with ergot derivative dopamine agonists. © 2004 Movement Disorder Society     

Long-term study of ropinirole patch in Parkinson's disease patients with/without basal l-dopa

IntroductionA dopamine agonist patch could be an important treatment option for Parkinson's disease. This study evaluated the long-term efficacy and safety of the ropinirole hydrochloride patch. The steady state plasma ropinirole concentration was also assessed.MethodsIn a multicenter, open-label, uncontrolled study, Parkinson's disease patients with/without basal levodopa and with/without prior dopamine agonist therapy (any of these four regimens) received application of a ropinirole patch once daily for up to 52 weeks with unforced titration from 8 to 64 mg. For patients with prior dopamine agonist therapy, the initial dose of ropinirole patch was determined from the prior dopamine agonist dose by using a conversion table.ResultsMost adverse events were mild or moderate. All application site adverse events were mild, except for moderate application site erythema in one patient. In patients with prior dopamine agonist therapy, switching to ropinirole patch did not lead to a significant early increase of adverse events. A change from baseline in the UPDRS Part III total score, the primary efficacy endpoint, showed improvement until Week 16 compared with baseline, followed by little subsequent change until Week 52, indicating maintenance of efficacy. The plasma ropinirole concentration was at steady state throughout the study period and showed a dose-proportional increase.ConclusionOnce-daily application of ropinirole patch showed long-term efficacy and safety (52 weeks) for Parkinson's disease. Switching from other dopamine agonists to ropinirole patch was effective and safe. The plasma ropinirole concentration was at steady state throughout the study period and showed a dose-proportional increase.     

Jeu d’argent problématique et responsabilité pénale

ObjectivesIn total, 14% to 30 % of individuals with gambling disorder engage in illegal acts to finance such behavior. This clinical situation could be explained by higher gambling severity, associated substance use disorder, antisocial personality disorder and economic factors (debts, financial problems). The present work focuses, more broadly, on criminal responsibility of problematic gamblers.MethodsWe will discuss this question through different typical situations that medical experts of criminal responsibility may have to face. We will address each of the following cases: 1) isolated problematic gambling; 2) problematic gambling associated with antisocial personality disorder; 3) problematic gambling associated with a manic episode; 4) problematic gambling associated with substance use disorders; and 5) problematic gambling associated wiht dopamine agonist treatment.ResultsIsolated problematic gambling, (not associated with any psychiatric or addictive disorder): it seems consensual that individuals committing infractions in this case are criminally responsible. However, impeded ability to action control and possible sentence attenuation could be discussed in case of severe gambling disorder. Problematic gambling associated with antisocial personality disorder: if the penal offence reports solely to personality disorder, criminal responsibility would be attributed. However, if illegal or violent acting is directly linked to co-cocurrent delusional symptoms, it could be a cause of criminal non-responsibility. Problematic gambling associated with manic episode: manic episode related offence could lead to negation of criminal responsibility, while a hypomanic episode may provide grounds for sentence reduction. Problematic gambling associated with substance use disorders: in France, addiction is not considered to remove nor to impede a person's ability to understand or control his actions and is excluded from criminal non-responsibility causes. However, substance induced delusional or confusional episodes could abolish a subject's discernment or his ability to control his actions yielding to penal non-responsibility. Problematic gambling associated with dopamine agonist treatment: Criminal responsibility for dopamine agonist induced gambling related illegal acts is still controversial. Nevertheless, people committing an infraction linked to associated dementia or dopamine agonist induced mania should be considered as criminally non-responsible.ConclusionsSome clinical dimensions such as craving intensity, compulsivity, disorder's severity, volitional control might be forensic targets to assess criminal responsibility.     

Milestones in Parkinson's disease therapeutics

In the mid‐1980s, the treatment of Parkinson's disease was quite exclusively centered on dopatherapy and was focusing on dopamine systems and motor symptoms. A few dopamine agonists and a monoamine oxidase B inhibitor (selegiline) were used as adjuncts in advanced Parkinson's disease. In the early 2010s, levodopa remains the gold standard. New insights into the organization of the basal ganglia paved the way for deep brain stimulation, especially of the subthalamic nucleus, providing spectacular improvement of drug‐refractory levodopa‐induced motor complications. Novel dopamine agonists (pramipexole, ropinirole, rotigotine), catecholmethyltransferase inhibitors (entacapone), and monoamine oxidase B inhibitors (rasagiline) have also been developed to provide more continuous oral delivery of dopaminergic stimulation in order to improve motor outcomes. Using dopamine agonists early, before levodopa, proved to delay the onset of dyskinesia, although this is achieved at the price of potentially disabling daytime somnolence or impulse control disorders. The demonstration of an antidyskinetic effect of the glutamate antagonist amantadine opened the door for novel nondopaminergic approaches of Parkinson's disease therapy. More recently, nonmotor symptoms (depression, dementia, and psychosis) have been the focus of the first randomized controlled trials in this field. Despite therapeutic advances, Parkinson's disease continues to be a relentlessly progressive disorder leading to severe disability. Neuroprotective interventions able to modify the progression of Parkinson's disease have stood out as a failed therapeutic goal over the last 2 decades, despite potentially encouraging results with compounds like rasagiline. Newer molecular targets, new animal models, novel clinical trial designs, and biomarkers to assess disease modification have created hope for future therapeutic interventions. © 2011 Movement Disorder Society     

Effects of dopamine agonist dose and gender on the prognosis of impulse control disorders in Parkinson's disease

IntroductionCross-sectional studies have demonstrated that Parkinson's disease patients have an increased risk of impulse control disorders, and that the disorders frequently co-exist with depressive symptoms. There have been no previous large-scale prospective studies investigating predictive and prognostic factors of these disorders.MethodsA population of 290 Parkinson's disease patients was studied at baseline and approximately 15 months later. The same screening methodology was used at both time-points (demographic and medication data together with the Questionnaire for Impulsive-compulsive Disorders in Parkinson's disease and the Beck Depression Inventory). The data was analyzed separating patients with and without impulse control disorders at baseline to obtain clinically useful prognostic factors.ResultsIn patients who had impulse control disorders at baseline (n = 119), high dopamine agonist dose was associated with the presence of disorders at follow-up. Dopamine agonist levodopa equivalent daily dose over 160 mg was significantly associated with impulse control disorders with a positive predictive value of 92.5% (95% confidence interval 79.6%–98.4%). In addition, females had a better prognosis of impulse control disorders compared to males. The development of novel impulse control disorders (no disorder at baseline, disorder at follow-up) was associated with a concurrent increase in depression scores.ConclusionsThe results suggest that dopamine agonist dose and gender are associated with the prognosis of impulse control disorders. Symptoms of depression emerge together with novel impulse control disorders in Parkinson's disease.     

Aripiprazole,jeu pathologique et sexualité compulsive

IntroductionAripiprazole, an atypical or second-generation antipsychotic, is usually well tolerated. It is an approved treatment for schizophrenia and mania in bipolar disorder type 1. Unlike the other antipsychotics, it has high affinity agonist properties for dopamine D2 and D3 receptors. It has also 5-HT1A partial agonist and 5-HT2A antagonist properties. Aripiprazole is a first or second line treatment frequently used because it has reduced side effects such as weight gain, sleepiness, dyslipidemia, insulin resistance, hyperprolactinemia and extrapyramidal symptoms.Case-reportWe report the case of a 28-year-old male patient diagnosed with schizoid personality disorder. He was a moderate smoker with occasional social gambling habits. After several psychotic episodes, he was first treated with risperidone, but he experienced excessive sedation, decreased libido, erectile dysfunction and was switched to 15 mg aripiprazole. He developed an addiction habit for gambling at casino slot machines. Due to large gambling debts, he requested placement on a voluntary self-exclusion list. Thereafter, he turned his attention towards scratch card gambling. The patient described his experience of gambling as a “hypnotic state”. He got several personal loans to obtain money to continue gambling. He was then referred to an addiction unit. Before being treated with aripiprazole, he was an exclusive heterosexual with a poor sexual activity. Under treatment, he switched to a homosexual behavior with hypersexuality, unprotected sex and sadomasochistic practices. The craving for gambling and compulsive sexual behavior ceased two weeks after aripiprazole was discontinued and he was switched to amisulpride. Thereafter, he reported a return to a heterosexual orientation.DiscussionCompulsive behaviors such as gambling, hypersexuality and new sexual orientation are common in patients with Parkinson's disease treated with dopaminergic agonists. These behaviors involve the reward system, with an enhanced dopaminergic activity in the mesolimbic pathways and occur more frequently in young subjects, males with previous gambling habits and tobacco use. A few cases of aripiprazole-induced pathological gambling as well as aripiprazole-induced hypersexuality have been reported. To our knowledge, we are the first to report a case of gambling disorder associated with hypersexuality and change of sexuality orientation. Aripiprazole is the only antipsychotic with agonist properties for the D2 dopamine receptor. It may also act as an enhancer in the mesolimbic dopaminergic pathways. Aripiprazole also has 5-HT1A partial agonist and 5-HT2A antagonist properties that may promote sexual activity.ConclusionAripiprazole is an antipsychotic associated with reduced side effects compared to other antipsychotics. We report the case of a patient who experienced gambling disorder, hypersexuality and a new sexual orientation under treatment. These side effects are little known. They are usually difficult for patients to mention due to feelings of guilt. The consequences on social life, family and health may be serious. Clinicians and patients should be aware about the possible issue of these behavior disorders with aripiprazole.