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Impulsive and compulsive behaviors in Parkinson's disease.

Zhang G, Zhang Z, Liu L, Yang J, Huang J, Xiong N, Wang T - Front Aging Neurosci (2014)

Bottom Line: Treatment of ICBs is still a great challenge for clinicians.The exact pathophysiological mechanisms of ICBs in PD remains poorly understood.Further researches are needed not only to study the pathogenesis, prevalence, features, and risk factors of ICBs, but to find efficacious therapy for patients with these devastating consequences.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.

ABSTRACT

Background: Impulsive and compulsive behaviors (ICBs) are a heterogeneous group of conditions that may be caused by long-term dopaminergic replacement therapy (DRT) of Parkinson's disease (PD). The spectrum of ICBs includes dopamine dysregulation syndrome (DDS), punding, and impulse control disorders (ICDs).

Contents: We made a detailed review regarding the epidemiology, pathology, clinical characteristics, risk factors, diagnosis as well as treatment of ICBs.

Results: The prevalence of ICBs in PD patients is approximately 3-4% for DDS, 0.34-4.2% for punding, and 6-14% for ICDs, with higher prevalence in Western populations than in Asian. Those who take high dose of levodopa are more prone to have DDS, whereas, ICDs are markedly associated with dopamine agonists. Different subtypes of ICBs share many risk factors such as male gender, higher levodopa equivalent daily dose, younger age at PD onset, history of alcoholism, impulsive, or novelty-seeking personality. The Questionnaire for Impulsive-Compulsive Disorder in Parkinson's Disease-Rating Scale seems to be a rather efficacious instrument to obtain relevant information from patients and caregivers. Treatment of ICBs is still a great challenge for clinicians. Readjustment of DRT remains the primary method. Atypical antipsychotics, antidepressants, amantadine, and psychosocial interventions are also prescribed in controlling episodes of psychosis caused by compulsive DRT, but attention should be drawn to balance ICBs symptoms and motor disorders. Moreover, deep brain stimulation of the subthalamic nucleus might be a potential method in controlling ICBs.

Conclusion: The exact pathophysiological mechanisms of ICBs in PD remains poorly understood. Further researches are needed not only to study the pathogenesis, prevalence, features, and risk factors of ICBs, but to find efficacious therapy for patients with these devastating consequences.

No MeSH data available.


Related in: MedlinePlus

The flowchart of management of ICBs in Parkinson’s disease. To prevent ICBs occurring, closer follow-up and monitoring are essential. Once ICBs are diagnosed, the first-choice is adjustment of dose of DAs and levodopa, but this requires a good balance between ICBs symptoms and motor disorders. For ICDs, D3 agonists should be reduced; for DDS, the dose of levodopa is considered to be cut down. With regard to punding, selegiline, which enhances the levodopa action and has amphetamine-like metabolites, and bedtime DRT should be withdrawn as well as reducing levodopa dose. In case motor disorder and psychopathic symptoms occur, levodopa may be useful for ICDs, and D3 agonists or entacapone may alleviate DDS and punding as well as antidepressants, antipsychotics, and amantadine. However, one should be ever vigilant that these could trigger or worsen concomitant disorders. Antiandrogen cyproterone should be considered for hypersexuality, especially when there are no other effective drugs. Atypical neuroleptic drugs could also be used for ICBs, such as olanzapine or quetiapine, especially for punding patients presenting with psychosis or reduced sleep time. Besides, cognitive-behavioral therapies have been evaluated as an efficacious method. Supposing that all interventions discussed above fail to control symptoms, DBS or DBS plus DRT could also be considered. Moreover, jejunal levodopa infusion was recently found to be effective for ICBs, whereas the availability was merely evaluated in small sample, and thus further larger clinical studies are still needed.
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Figure 1: The flowchart of management of ICBs in Parkinson’s disease. To prevent ICBs occurring, closer follow-up and monitoring are essential. Once ICBs are diagnosed, the first-choice is adjustment of dose of DAs and levodopa, but this requires a good balance between ICBs symptoms and motor disorders. For ICDs, D3 agonists should be reduced; for DDS, the dose of levodopa is considered to be cut down. With regard to punding, selegiline, which enhances the levodopa action and has amphetamine-like metabolites, and bedtime DRT should be withdrawn as well as reducing levodopa dose. In case motor disorder and psychopathic symptoms occur, levodopa may be useful for ICDs, and D3 agonists or entacapone may alleviate DDS and punding as well as antidepressants, antipsychotics, and amantadine. However, one should be ever vigilant that these could trigger or worsen concomitant disorders. Antiandrogen cyproterone should be considered for hypersexuality, especially when there are no other effective drugs. Atypical neuroleptic drugs could also be used for ICBs, such as olanzapine or quetiapine, especially for punding patients presenting with psychosis or reduced sleep time. Besides, cognitive-behavioral therapies have been evaluated as an efficacious method. Supposing that all interventions discussed above fail to control symptoms, DBS or DBS plus DRT could also be considered. Moreover, jejunal levodopa infusion was recently found to be effective for ICBs, whereas the availability was merely evaluated in small sample, and thus further larger clinical studies are still needed.

Mentions: Though mounting data regarding ICBs have aroused great concerns in recent years, ICBs remain a great challenge in clinical practice (Figure 1). Vigilance in the prescribing physical symptom is of paramount importance. Exact prevalence rate of ICBs is still frequently underreported. As PD patients with ICBs have reduced insights into social consequences of their behaviors, it turns momentous to screen ICBs using specifically devised and validated diagnostic tools and to enquire relevant information from both patients and caregivers. Susceptibilities to ICBs in PD patients have been associated with specific demographic and clinical characteristics and abnormalities on functional neuroimaging studies including male gender, higher LEDD, young age at PD onset, personal or family history of alcoholism, and impulsive or novelty-seeking personalities. The pathology of PD, including the role of different neurotransmitters, likely plays a facilitative role in developing ICBs but the exact mechanisms remain to be established. Numerous studies have related ICBs to dopaminergic therapy. Imaging studies also provided additional evidence to strengthen the link. Given the potentially devastating consequences and lack of effective treatments for ICBs, preventive strategies do matter. Though ICBs have been considered as side effects resulting from DRT, levodopa remains the gold standard for symptomatic treatment in PD patients and should not be withheld from patients especially in whom sufficient symptomatic control cannot be otherwise obtained. Whether or not a DA should be used as early monotherapy largely depends on the perceived risk of dyskinesias – for which younger age is a major determinant (Antonini et al., 2009). Readjustment of DRT dose is still the main way to prevent and control ICBs, but attention should be drawn to balance ICBs symptoms and motor disorders. Moreover, atypical antipsychotics, antidepressants, amantadine, and psychosocial interventions can also be prescribed in controlling episodes of psychosis caused by compulsive DRT use with cautiousness because these drugs may also induce variable degree of motor function worsening. In addition to the pharmacal therapies described above, STN-DBS may be another efficacious therapy for advanced PD patients with the potential not only to allow significant reductions in drug dose but to improve “off”-medication motor symptoms (Table S3 in Supplementary Material). Furthermore, Williams et al. (2010) reported that surgery plus best medical therapy improved patient self-reported quality of life more than best medical therapy alone in patients with advanced PD. All in all, the use of emerging, empirically validated treatments for ICBs should be considered, particularly for patients whose discontinuation of DA therapy is not a viable option. Despite many achievements have been acquired, several unanswered questions remain. Firstly, what are the main reasons that differentiate PD patients that develop ICBs from those patients do not develop ICBs even if they receive the same medication? Although we have found many risk factors for the development of ICBs, this question is still unanswered at the level of neuronal function. Furthermore, why do different PD patients develop differing ICBs presentations? Individual susceptibilities, disease process, and dopaminergic medications might all contribute to the occurrence of diverse ICBs, but the accurate nosogenesis should be further investigated. Finally, what is the relationship between ICDs, DDS, punding, and substance abuse? Though familiar clinical risk factors and some common grounds have been observed, the key factors leading PD patients to substance abuse but not ICDs, DDS, or punding has not been illustrated. In conclusion, the current goal is to determine the exact mechanisms in the pathogenesis of ICBs in PD patients, and then find the corresponding therapy to offer robust motor benefit without producing ICDs or other serious side effects.


Impulsive and compulsive behaviors in Parkinson's disease.

Zhang G, Zhang Z, Liu L, Yang J, Huang J, Xiong N, Wang T - Front Aging Neurosci (2014)

The flowchart of management of ICBs in Parkinson’s disease. To prevent ICBs occurring, closer follow-up and monitoring are essential. Once ICBs are diagnosed, the first-choice is adjustment of dose of DAs and levodopa, but this requires a good balance between ICBs symptoms and motor disorders. For ICDs, D3 agonists should be reduced; for DDS, the dose of levodopa is considered to be cut down. With regard to punding, selegiline, which enhances the levodopa action and has amphetamine-like metabolites, and bedtime DRT should be withdrawn as well as reducing levodopa dose. In case motor disorder and psychopathic symptoms occur, levodopa may be useful for ICDs, and D3 agonists or entacapone may alleviate DDS and punding as well as antidepressants, antipsychotics, and amantadine. However, one should be ever vigilant that these could trigger or worsen concomitant disorders. Antiandrogen cyproterone should be considered for hypersexuality, especially when there are no other effective drugs. Atypical neuroleptic drugs could also be used for ICBs, such as olanzapine or quetiapine, especially for punding patients presenting with psychosis or reduced sleep time. Besides, cognitive-behavioral therapies have been evaluated as an efficacious method. Supposing that all interventions discussed above fail to control symptoms, DBS or DBS plus DRT could also be considered. Moreover, jejunal levodopa infusion was recently found to be effective for ICBs, whereas the availability was merely evaluated in small sample, and thus further larger clinical studies are still needed.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4231987&req=5

Figure 1: The flowchart of management of ICBs in Parkinson’s disease. To prevent ICBs occurring, closer follow-up and monitoring are essential. Once ICBs are diagnosed, the first-choice is adjustment of dose of DAs and levodopa, but this requires a good balance between ICBs symptoms and motor disorders. For ICDs, D3 agonists should be reduced; for DDS, the dose of levodopa is considered to be cut down. With regard to punding, selegiline, which enhances the levodopa action and has amphetamine-like metabolites, and bedtime DRT should be withdrawn as well as reducing levodopa dose. In case motor disorder and psychopathic symptoms occur, levodopa may be useful for ICDs, and D3 agonists or entacapone may alleviate DDS and punding as well as antidepressants, antipsychotics, and amantadine. However, one should be ever vigilant that these could trigger or worsen concomitant disorders. Antiandrogen cyproterone should be considered for hypersexuality, especially when there are no other effective drugs. Atypical neuroleptic drugs could also be used for ICBs, such as olanzapine or quetiapine, especially for punding patients presenting with psychosis or reduced sleep time. Besides, cognitive-behavioral therapies have been evaluated as an efficacious method. Supposing that all interventions discussed above fail to control symptoms, DBS or DBS plus DRT could also be considered. Moreover, jejunal levodopa infusion was recently found to be effective for ICBs, whereas the availability was merely evaluated in small sample, and thus further larger clinical studies are still needed.
Mentions: Though mounting data regarding ICBs have aroused great concerns in recent years, ICBs remain a great challenge in clinical practice (Figure 1). Vigilance in the prescribing physical symptom is of paramount importance. Exact prevalence rate of ICBs is still frequently underreported. As PD patients with ICBs have reduced insights into social consequences of their behaviors, it turns momentous to screen ICBs using specifically devised and validated diagnostic tools and to enquire relevant information from both patients and caregivers. Susceptibilities to ICBs in PD patients have been associated with specific demographic and clinical characteristics and abnormalities on functional neuroimaging studies including male gender, higher LEDD, young age at PD onset, personal or family history of alcoholism, and impulsive or novelty-seeking personalities. The pathology of PD, including the role of different neurotransmitters, likely plays a facilitative role in developing ICBs but the exact mechanisms remain to be established. Numerous studies have related ICBs to dopaminergic therapy. Imaging studies also provided additional evidence to strengthen the link. Given the potentially devastating consequences and lack of effective treatments for ICBs, preventive strategies do matter. Though ICBs have been considered as side effects resulting from DRT, levodopa remains the gold standard for symptomatic treatment in PD patients and should not be withheld from patients especially in whom sufficient symptomatic control cannot be otherwise obtained. Whether or not a DA should be used as early monotherapy largely depends on the perceived risk of dyskinesias – for which younger age is a major determinant (Antonini et al., 2009). Readjustment of DRT dose is still the main way to prevent and control ICBs, but attention should be drawn to balance ICBs symptoms and motor disorders. Moreover, atypical antipsychotics, antidepressants, amantadine, and psychosocial interventions can also be prescribed in controlling episodes of psychosis caused by compulsive DRT use with cautiousness because these drugs may also induce variable degree of motor function worsening. In addition to the pharmacal therapies described above, STN-DBS may be another efficacious therapy for advanced PD patients with the potential not only to allow significant reductions in drug dose but to improve “off”-medication motor symptoms (Table S3 in Supplementary Material). Furthermore, Williams et al. (2010) reported that surgery plus best medical therapy improved patient self-reported quality of life more than best medical therapy alone in patients with advanced PD. All in all, the use of emerging, empirically validated treatments for ICBs should be considered, particularly for patients whose discontinuation of DA therapy is not a viable option. Despite many achievements have been acquired, several unanswered questions remain. Firstly, what are the main reasons that differentiate PD patients that develop ICBs from those patients do not develop ICBs even if they receive the same medication? Although we have found many risk factors for the development of ICBs, this question is still unanswered at the level of neuronal function. Furthermore, why do different PD patients develop differing ICBs presentations? Individual susceptibilities, disease process, and dopaminergic medications might all contribute to the occurrence of diverse ICBs, but the accurate nosogenesis should be further investigated. Finally, what is the relationship between ICDs, DDS, punding, and substance abuse? Though familiar clinical risk factors and some common grounds have been observed, the key factors leading PD patients to substance abuse but not ICDs, DDS, or punding has not been illustrated. In conclusion, the current goal is to determine the exact mechanisms in the pathogenesis of ICBs in PD patients, and then find the corresponding therapy to offer robust motor benefit without producing ICDs or other serious side effects.

Bottom Line: Treatment of ICBs is still a great challenge for clinicians.The exact pathophysiological mechanisms of ICBs in PD remains poorly understood.Further researches are needed not only to study the pathogenesis, prevalence, features, and risk factors of ICBs, but to find efficacious therapy for patients with these devastating consequences.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.

ABSTRACT

Background: Impulsive and compulsive behaviors (ICBs) are a heterogeneous group of conditions that may be caused by long-term dopaminergic replacement therapy (DRT) of Parkinson's disease (PD). The spectrum of ICBs includes dopamine dysregulation syndrome (DDS), punding, and impulse control disorders (ICDs).

Contents: We made a detailed review regarding the epidemiology, pathology, clinical characteristics, risk factors, diagnosis as well as treatment of ICBs.

Results: The prevalence of ICBs in PD patients is approximately 3-4% for DDS, 0.34-4.2% for punding, and 6-14% for ICDs, with higher prevalence in Western populations than in Asian. Those who take high dose of levodopa are more prone to have DDS, whereas, ICDs are markedly associated with dopamine agonists. Different subtypes of ICBs share many risk factors such as male gender, higher levodopa equivalent daily dose, younger age at PD onset, history of alcoholism, impulsive, or novelty-seeking personality. The Questionnaire for Impulsive-Compulsive Disorder in Parkinson's Disease-Rating Scale seems to be a rather efficacious instrument to obtain relevant information from patients and caregivers. Treatment of ICBs is still a great challenge for clinicians. Readjustment of DRT remains the primary method. Atypical antipsychotics, antidepressants, amantadine, and psychosocial interventions are also prescribed in controlling episodes of psychosis caused by compulsive DRT, but attention should be drawn to balance ICBs symptoms and motor disorders. Moreover, deep brain stimulation of the subthalamic nucleus might be a potential method in controlling ICBs.

Conclusion: The exact pathophysiological mechanisms of ICBs in PD remains poorly understood. Further researches are needed not only to study the pathogenesis, prevalence, features, and risk factors of ICBs, but to find efficacious therapy for patients with these devastating consequences.

No MeSH data available.


Related in: MedlinePlus