Long term follow-up of Parkinson's disease patients with impulse control disorders

doi:10.1016/j.parkreldis.2010.02.006

Parkinsonism & Related Disorders

Volume 16, Issue 5, June 2010, Pages 334-337

https://doi.org/10.1016/j.parkreldis.2010.02.006 Get rights and content

Abstract

Objective

Impulse control disorders (ICDs) are mainly triggered by dopaminergic therapy in Parkinson's disease (PD). Previously, we failed to identify a relationship between the types of dopaminergic therapy and occurrence of ICDs in 33 PD patients. In this study, we aim to evaluate the outcome of ICD behaviors in the same patient group.

Patients and methods

Among 33 patients with ICDs, 22 patients were included. Demographics, dopaminergic therapy and disease severity were compared between two time points (Time 1: time of diagnosis of ICD, Time 2: last visit) and between patients who recovered from ICDs and with ongoing ICDs. Types of antipsychotic and antidepressant medication were noted.

Results

Mean follow-up period was 43.2 months. At Time 2 mean dopamine agonist (DA) dose was significantly lower, levodopa dose and total UPDRS score was significantly higher. ICDs were dissolved in 16 patients (73%), but persisted in six (27%). In ICD(+) subgroup, DA doses in Time 1 was found significantly higher than ICD(−). However, age, PD severity, disease duration and levodopa dosage were similar. Fourteen patients were prescribed atypical antipsychotics and 13 antidepressants. In ICD(+) group, symptoms of ICDs were mainly increased libido and compulsive eating.

Conclusions

Although we studied a small number of patients the recovery from compulsive behaviors may be associated with the decrease in DA dosage and increase in levodopa. Furthermore, majority were given antipsychotic and/or antidepressant drugs. It is difficult to speculate which strategy could be more effective on the improvement of ICDs in such a small group. In patients who were on high doses of DA, ICDs could be persistent.

Introduction

There has been increasing interest in impulse control disorders (ICDs) that affect a small group of patients with Parkinson's disease (PD) on dopaminergic replacement therapy (DRT). These compulsive behaviors are composed of obsessive shopping [1], [2], pathological gambling [1], [3], [4], hypersexuality [1], [3] and compulsive eating [5]. Furthermore, punding [6] and dopamine dysregulation syndrome [7], [8] are frequently associated with ICD behaviors in such patients.

The research on the matter have implicated that dopamine agonist (DA) [1], [2], [3], [5], [7], [8], [9], [10], [11] and to a much lesser extent levodopa [12] usage are the main risk factors for the development of ICD behaviors. In a previous study, we identified the demographics, clinical characteristics and effects of DRT on a group of PD patients with various ICDs [13]. We failed to show any association between a particular type of DRT and the development of ICDs in this small group of patients.

To date, there was only one report published by Mamikonyan et al. regarding long term follow-up of ICDs in PD patients [14]. Herein, we aimed to present the characteristics of 22 patients from the previous study who were clinically followed-up for a time period. On follow-up, patients were evaluated for the symptoms of ICDs, doses and types of previous and current dopaminergic therapy as well as the properties of antipsychotic and antidepressant medications, if added. Additionally, the differences between the patients who recovered from ICD and patients with persistent ICD were noted.

Section snippets

Materials and methods

In a previous study [13], among 554 PD patients seen in our Movement Disorders outpatient clinic between years 2003 and 2007, 33 patients with ICD behaviors were identified using a semi-structured questionnaire directed to patients and their caregivers based on the DSM IV criteria and previously published studies [7], [15], [16], [17]. In that study, in addition to various ICDs, punding and/or dopamine dysregulation syndrome were gathered under the topic of ICD. Patients scoring less than 25

Statistics

Data were entered and analyzed using SPSS for windows 11.0. Comparisons for clinical variables of PD patients with ICDs between Time 1 and Time 2 were performed by using Mann–Whitney U and Wilcoxon Signed Ranks Tests, as appropriate. The threshold level for statistical significance was established at p < 0.05.

Results

The mean age of 22 patients (18 men, 81.8%) was 57.3 ± 10.1 (range: 42–79) years. The mean follow-up period of them was 43.2 ± 16.16 months (range: 8–62). Age at onset of PD was 46.7 ± 9.3 (range: 33–70) and disease duration 10.8 ± 4.5 (range: 4–21) years. Other demographical, clinical and medication-related features are given in Table 1. The mean DA dose was significantly lower, but levodopa dose was higher in Time 2 than those of Time 1, as expected. According to the UPDRS (I-III) scores at

Discussion

In the current study, we evaluated the outcome of compulsive behaviors developed in 22 PD patients comprising a mean follow-up period of 43 months. It was noted that in nearly 73 percent of PD patients ICD behaviors were completely recovered after reducing dosage of DA drugs. That is generally accepted as the first line management strategy of ICDs. Fifteen of our patients were already on low doses of DA therapy at the last visit.

In our series, the daily doses of DA drugs were found to be

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Addictions involve a spectrum of behaviors that encompass features of impulsivity and compulsivity, herein referred to as impulsive-compulsive spectrum disorders (ICSDs). The etiology of ICSDs likely involves a complex interplay among neurobiological, psychological and social risk factors. Neurobiological risk factors include the status of the neuroanatomical circuits that govern ICSDs. These circuits can be altered by disease, as well as exogenous influences such as centrally-acting pharmacologics. The ‘poster child’ for this scenario is Parkinson’s disease (PD) medically managed by pharmacological treatments. PD is a progressive neurodegenerative disease that involves a gradual loss of dopaminergic neurons largely within nigrostriatal projections. Replacement therapy includes dopamine receptor agonists that directly activate postsynaptic dopamine receptors (bypassing the requirement for functioning presynaptic terminals). Some clinically useful dopamine agonists, e.g., pramipexole and ropinirole, exhibit high affinity for the D2/D3 receptor subtypes. These agonists provide excellent relief from PD motor symptoms, but some patients exhibit debilitating ICSD. Teasing out the neuropsychiatric contribution of PD-associated pathology from the drugs used to treat PD motor symptoms is challenging. In this review, we posit that modern clinical and preclinical research converge on the conclusion that dopamine replacement therapy can mediate addictions in PD and other neurological disorders. We provide five categories of evidences that align with this position: (i) ICSD prevalence is greater with D2/D3 receptor agonist therapy vs PD alone. (ii) Capacity of dopamine replacement therapy to produce addiction-like behaviors is independent of disease for which the therapy is being provided. (iii) ICSD-like behaviors are recapitulated in laboratory rats with and without PD-like pathology. (iv) Behavioral pathology co-varies with drug exposure. (v) ICSD Features of ICSDs are consistent with agonist pharmacology and neuroanatomical substrates of addictions. Considering the underpinnings of ICSDs in PD should not only help therapeutic decision-making in neurological disorders, but also apprise ICSDs in general.
Neurobiology of cue-reactivity, craving, and inhibitory control in non-substance addictive behaviors
2020, Journal of the Neurological Sciences
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PET studies of Parkinson’s disease patients with gambling disorder and other non-substance addictive behaviors or ICDs show reduced D2/3 binding potentials in striatal regions, including during gambling or confrontation with behavior-related cues [72,97,107,128]. Reduction of dopaminergic medication may lead to decreases in symptom severity of non-substance addictive behaviors in these patients [129], although the open-label nature of such data limits the attribution of the decreases to the medication. For example, alternate explanations such as cognitive distortion and expectancies (e.g., as seen in placebo or nocebo responses) should be considered [130–132].
Non-substance addictive behaviors may involve repetitive rewarding behaviors including gambling, gaming, sexual activities, internet-use, and buying-shopping. In addictions, there exists diminished control over participation in the behaviors and continuation of the behaviors despite experiencing negative consequences. Addictive participation in behaviors typically results in distress and functional impairment in personal, relational, occupational, educational, or other life domains. Increases in cue-reactivity and craving and decreases in inhibitory control may represent pivotal mechanisms in addictions, especially when behavior-specific cues are present. Similar to substance-use disorders, alterations in brain networks related to reward processing, executive functioning, salience attribution, and habit formation and in neurochemical pathways that may include dopamine, serotonin, opioids, and other neurotransmitters may represent neurobiological factors involved in the development and maintenance of addictive behaviors. Although there has been substantial progress in research on the neurobiologies of addictive behaviors, science is still at an early stage of understanding the potential neurobiological mechanisms related to specific non-substance addictive behaviors. Considerations for future directions in research on non-substance addictive behaviors, with a view on common and distinct neurobiological foundations of specific disorders, are discussed.
Sexual Dysfunctions in Parkinson's Disease: An Underrated Problem in a Much Discussed Disorder
2017, International Review of Neurobiology
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Some patients may develop intense feeling of jealousy and suicidal ideation, while paraphilia, or repetitive and intense sexual urge in socially inappropriate settings, calling for legal interventions, may occasionally be observed (Bronner et al., 2003; Harvey, 1988; Riley, 2002). Aberrations in the form of qualitative alterations in sexuality like, transvestism, or gender identity disorders have also been reported (Courty, Durif, Zenut, Courty, & Lavarenne, 1997; Odiyoor, Kobylecki, Hackett, Silverdale, & Kellett, 2009; Sohtaoglu, Demiray, Kenangil, Ozekmekci, & Erginoz, 2010). Interestingly, it is seen that though most of the components of ICD disappear with discontinuation of dopaminergic therapy, HS tend to persist for a longer time (Cools, 2006; Evans & Lees, 2004).
Sexual dysfunctions (SDs) are one of the most neglected nonmotor symptoms in Parkinson's disease (PD). A number of reasons including social and cultural factors might explain, at least partially, why SD is still one of the most underrecognized aspects of the condition after 200 years since the very first description by James Parkinson. SD has not been extensively investigated, however, a number of studies have shown a high prevalence of decreased libido, orgasmic dysfunction in both men and women with PD, and erectile dysfunction in male subjects. Moreover, SD in PD also comprises the increasingly recognized hypersexuality that is often associated with PD treatment. Taken together, SD in PD includes a remarkable range of symptoms and conditions that often require a multidisciplinary approach regarding assessment, investigation, and treatment.
Pathological gambling in Parkinson's disease. A comprehensive review
2013, Parkinsonism and Related Disorders
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.
Effects of dopamine agonist dose and gender on the prognosis of impulse control disorders in Parkinson's disease
2012, Parkinsonism and Related Disorders
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Finally, Sohtaoğlu et al. [5] examined 22 Turkish PD patients with ICDs and the problems resolved in 16 patients during 43 months. Interestingly, the results by Sohtaoğlu et al. also suggested that lower dopamine agonist doses at baseline may be associated with resolved ICDs [5]. Our study, with 290 Finnish PD patients and 119 patients with ICDs at baseline, suggests that larger agonist doses are associated with more persistent ICDs.
Cross-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.
A 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.
In 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.
The 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.
Management of impulse control disorders in Parkinson's disease
2016, International Psychogeriatrics

View all citing articles on Scopus

^☆: The review of this paper was entirely handled by an Associate Editor, Jonathan Carr.

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Long term follow-up of Parkinson's disease patients with impulse control disorders☆

Abstract

Objective

Patients and methods

Results

Conclusions

Introduction

Section snippets

Materials and methods

Statistics

Results

Discussion

Parkinsonism Relat Disord

Parkinsonism Relat Disord

Parkinsonism Relat Disord

Association of dopamine agonist use with impulse control disorders in Parkinson's disease

Arch Neurol

Clinical features associated with impulse control disorders in Parkinson disease

Neurology

Prospective prevalence of pathological gambling and medication association in Parkinson's disease

Neurology

Impulse control disorders and pathological gambling in patients with Parkinson disease

Neurologist

Compulsive eating and weight gain related to dopamine agonist use

Mov Disord

Dopamine dysregulation syndrome in Parkinson's disease

Curr Opin Neurol

Hedonistic homeostatic dysregulation in patients with Parkinson's disease on dopamine replacement therapies

J Neurol Neurosurg Psychiatr

Factors influencing susceptibility to compulsive dopaminergic drug use in Parkinson's disease

Neurology

Pathological gambling in Parkinson's disease: risk factors and differences from dopamine dysregulation. An analysis of published case series

Mov Disord

Pathological gambling caused by drugs used to treat Parkinson disease

Arch Neurol

Pathologic gambling in Parkinson's disease: a behavioral manifestation of pharmacologic treatment?

Mov Disord