Understanding Impulse Control Disorders in Parkinson Disease: Developments and Treatments

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Clinicians can change treatment from dopamine agonists to levodopa, which is associated with a lower incidence of impulse control disorders but also has its own adverse effect profile.
Clinicians can change treatment from dopamine agonists to levodopa, which is associated with a lower incidence of impulse control disorders but also has its own adverse effect profile.

Many people living with Parkinson disease (PD) may also suffer from impulse control disorders (ICDs). Although ICDs can be frequently observed within PD, the research offering an explanation for this occurrence has been less than satisfying. However, recent studies led by Aleksander H. Erga, clinical psychologist and PhD candidate at the Norwegian Centre for Movement Disorders, Stavanger University Hospital, aims to change that. On the basis of their findings, Erga and colleagues found that patients with PD have a 3-fold increase in the risk of developing ICDs compared with matched control patients.1,2

Mechanisms of ICDs in Parkinson Disease

ICDs comprise impulsive and compulsive behaviors. Impulsive behaviors, such as gambling and shopping for expensive items, pertain to actions that a person cannot resist. These behaviors provide an immediate feeling of pleasure or reward. Compulsive behavior, such as double-checking the time, tapping one's fingers, and counting items, pertains to an urge to carry out an action repetitively and in a very specific way.3

So, why are impulsive and compulsive behaviors common among people with PD? This can be partly explained by the reduction in dopamine levels in the brain, which is linked to the development of PD. Loss of dopamine leads to movement issues such as tremors and difficulty walking. Dopamine is also associated with the brain's motivation and reward centers. Some people with altered dopamine levels may find it challenging to regulate rewarding or pleasurable actions and impulsive behaviors.4

PD treatments, and in particular, dopamine agonists (DAs), are specifically designed to affect dopamine levels in the brain. According to Professor David Dexter, PhD, deputy director of the Parkinson's UK charity, standard PD treatment enhances dopamine function in 2 main dopaminergic pathways in the brain: the nigrostriatal system, which controls movement and degenerates in Parkinson's, and the mesolimbic system, which controls emotion and behavior. "While standard treatment makes up for the lost dopamine in the nigrostriatal system in Parkinson's, and hence improves movement, it also enhances dopamine function in the mesolimbic pathway, which can trigger hallucinations and ICDs in some susceptible individuals," he explained.

Using data from the Norwegian ParkWest study, Erga and colleagues also showed an association between DA use and a 7-fold increase risk of developing an ICD.2 "Studies from large parts of the world have also consistently found a strong association between ICDs and dopamine replacement therapy...which is the most commonplace treatment for PD. Studies have shown that this medication can result in loss of behavioral volition that characterizes the ICD pathology," Erga told Neurology Advisor.

Determining PD Patients at Risk for ICDs

Certain demographic factors place some people with PD at an increased risk of developing ICDs. In particular, those who are of a young age, male, smoke, have exposure to alcohol abuse or gambling, or have a history of addictive behavior are at greater risk of developing impulse control issues.5

New findings in genetic research also reveal an interesting perspective on the identification of at-risk patients.2 "The latest development within genetic research highlights that premorbid factors may be important in ICD development when exposed to dopamine replacement," said Erga.

Specifically, Erga has researched single-nucleotide polymorphisms (SNPs) and their role in ICDs within PD. SNPs commonly occur in the human genome and mostly have no effect on a person's development and health; researchers even use SNPs as biomarkers to better understand health and to locate disease-associated genes. Now, researchers such as Erga are investigating whether and how SNPs are associated with risk for ICD development.

"This field of research is exciting," said Erga, "as it may be a promising method to guide clinical practice. We recently published a study investigating polymorphisms in Parkinson's patients with ICDs. Eleven SNPs were significantly associated with ICDs, although several only slightly so. These SNPs were from the dopaminergic, opioid, glutamatergic, and serotonergic pathways."

Erga's study replicated a previously existing clinical-genetic model and included 4 SNPs from the dopaminergic and opioid pathways. "In this [new] model, we increased the level of prediction of ICD from 68% to 81%. These results provide additional supporting clinical-genetic models for the identification of at-risk patients," shared Erga. Such models can help identify at-risk patients before dopamine replacement is initiated, and thus guide clinical practice.

Individualized Patient Management and Treatments

According to Erga, their findings have several implications on the management of PD: "These findings highlight the importance of patient information, caregiver information, and frequent screening of these symptoms. Patients who are prescribed dopamine replacement should be given information about ICDs. Their caregivers should also be provided information about possibly devastating side effects." He also urged clinicians to frequently use the Questionnaire for Impulsive Compulsive Disorders in Parkinson's disease to screen for ICDs.

Treatment of ICDs in PD remains a clinical challenge. Although Erga identified potential treatments for ICD in PD, he said research in this area is still in its early stages. "Other pharmacological approaches are currently being investigated, including amantadine and naltrexone. Cognitive behavioral therapy has also been shown to improve symptom severity, but further studies are needed before clear clinical recommendations can be made," he said.

In the meantime, clinicians can reduce DA doses to alleviate disability while reducing the risk for ICDs, suggested Professor Dexter. He added that clinicians can also change treatment from DA to levodopa, which is associated with a lower incidence of ICDs but also has its own adverse effect profile. Clinicians can also change to a first-generation (as opposed to second-generation) DA, for which the incidence of ICDs is less. In such instances, clinicians must monitor the patient's cardiovascular function. "Hopefully pharmaceutical companies develop a third-generation agonist without these side-effects," said Professor Dexter.

The situation with ICD treatment in PD is far from ideal. Whether one is at risk of developing ICDs or not, however, people with PD and their caretakers should be encouraged to openly talk to their physician about potential adverse effects and keep abreast of new developments within the field.

References

  1. Erga AH, Dalen I, Ushakova A, et al. Dopaminergic and opioid pathways associated with impulse control disorders in Parkinson's disease. Front Neurol. 2018;9:109.
  2. Erga AH, Alves G, Larsen JP, Tysnes OB, Pedersen KF. Impulsive and compulsive behaviors in Parkinson's disease: The Norwegian ParkWest study. J Parkinsons Dis. 2017;7(1):183-191.
  3. Impulsive and compulsive behaviour. Parkinson's UK. https://www.parkinsons.org.uk/information-and-support/impulsive-and-compulsive-behaviour. Updated June 2015. Accessed April 10, 2018.
  4. Henderson, W. How does dopamine affect Parkinson's disease?Parkinson's News Today. https://parkinsonsnewstoday.com/2017/01/09/dopamine-affect-parkinsons-disease/. January 9, 2017. Accessed.
  5. Impulsive and compulsive behaviour. Parkinson's UK. https://www.parkinsons.org.uk/information-and-support/impulsive-and-compulsive-behaviour. Accessed April 10, 2018.
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