Prevalence of Impulse Control Disorders among Adult Filipino Patients with Idiopathic Parkinson’s Disease seen at Jose R. Reyes Memorial Medical Center

Parkinson’s disease is a chronic, progressive, neurodegenerative disease characterized by loss of dopaminergic pigmented cells in the substantia nigra, locus cereuleus, and dorsal motor nucleus of the vagus¹. Core features of the disease are a tetrad of bradykinesia, rigidity, resting tremors and postural instability. The onset of symptoms usually starts between ages 45 and 70 with peak incidence in the sixth decade and male preponderance¹.

The following are the clinical subtypes of PD: 1. early disease onset (EDO): below age 55; 2. Tremor dominant (TD): onset at age 55 and above initially presenting with rest tremor over bradykinesia and rigidity; 3. Non-tremor dominant (NTD) or the akinetic rigid type: onset at age 55 and above with bradykinesia and with or without mild rest tremor; and 4. Rapid disease progression without dementia (RDP): death occurred in the first 10 years of symptoms irrespective of age ⁸.

Non-motor symptoms (NMS) of Parkinson’s disease are uncommonly recognized and often missed in neurologic consultations. These undertreated symptoms cause major disability for Parkinson patients. These symptoms occur at all stages of PD and are common with disease progression in severity and duration³. The most reported disabling symptoms of Parkinson’s disease are postural instability, dementia, insomnia, and drooling of saliva ³.

Impulse control disorders (ICDs) are pathogical behavioral patterns which include hypersexuality, compulsive eating or shopping, pathological gambling, repetitive mechanical activities (punding) or excessive compulsive overuse of dopaminergic drugs (dopamine dysregulation syndrome – DDS) that occurs in 15-20% of Parkinson patients⁶. These can be associated with the goal of being rewarded whether through experiencing pleasure and/or through material gain. This can be explained by the result of the damaged dopaminergic transmission with the reward-seeking behavior center in the brain (amygdala and nucleus accumbens) caused by PD pathology or the dopaminergic treatment itself. The hypersensitization of the ventral striatal circuitry due to enhanced ventral striatal dopamine release may be another pathological mechanism. Recent studies have demonstrated that the use of levodopa and dopamine agonists (particularly pramipexole), early onset of PD, substance abuse, depression, higher novelty-seeking personality traits and being male, promote higher risk of developing ICDs. Hypersexuality and pathologic gambling are the most common ICDs to occur ^{5, 6, 7}.

Impulse control disorders (ICDs) significantly affects the overall quality of life of Parkinson’s disease patients especially on the psychological and socioeconomic aspect. Currently, the prevalence of ICDs among adult Filipinos with idiopathic PD is unknown and less reported.

General Objective: The study is intended to determine the prevalence of Impulse Control Disorders (ICDs) and its severity among adult Filipino patients with idiopathic Parkinson’s disease seen at Jose R. Reyes Memorial Medical Center.

This study will identify risk factors and clinical correlates to these patients.

All consecutive adult Filipino patients with idiopathic PD seen from March 2015 – September 2015 at the outpatient department were screened for the study. A Movement Disorder specialist verified the diagnosis of PD using the UK Brain Bank diagnostic criteria.

A baseline neurologic examination of the subjects was done. Those subjects with cognitive dysfunction, psychiatric illness, and current medical conditions who are unable to answer the questionnaires and give consent were excluded from the study. The following variables for correlation with ICDs were considered in the study: Age, Sex, Duration and stage of illness, subtype of PD, type of anti-Parkinson medications, use of antipsychotics and antidepressants, and the treatment duration prior to onset of ICD symptoms.

We used the Questionnaire for Impulsive-Compulsive Disorders Questionnaire in Parkinson’s Disease-Rating Scale (QUIP-RS) was for screening the subjects. It is a validated questionnaire for detecting ICD symptoms and corresponding severity. It contains 7 sections on pathological gambling, hypersexuality, compulsive eating, compulsive buying, punding, hobbyism, and Parkinson’s disease medication use (Dopamine Dysregulation Syndrome)¹¹.

The Modified Hoehn and Yahr staging of Parkinson’s disease was done. With approval from author, Dr. Daniel Weintraub, the QUIP-RS was used.

Sixty-six (66) adult patients (31 males and 35 females) diagnosed with idiopathic Parkinson disease were examined. These included patients with mean age of 63.33±10.01, mean duration of PD for 4.39±2.54 years, and mean modified Hoehn and Yahr stage of 2.13±0.93. Most common Parkinson disease subtype was Tremor Dominant (TD) with 48.5% prevalence. Majority of the subjects were on levodopa + carbidopa drug regimen (48.5%) followed by combination of levodopa + carbidopa and anticholinergic agents (31.8%).

Using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease-Rating Scale (QUIP-RS), sixteen (16) out of 66 patients (24.2%) have ICD symptoms with the following incidence rates: hobbyism/ punding 56.25%, compulsive eating 50%, hypersexuality 18.75%, compulsive shopping 18.75, Dopamine dysregulation syndrome 18.75%, and gambling 12.5%. Overall average QUIP-RS score is 5.42 which may be interpreted as mild.

Analysis of risk factors versus occurrence of ICD symptoms revealed that there is no significant association of age with the development of ICD symptoms (x² 34.22; p = 0.231). The gender distribution is the same across categories of ICD (x² 0.078; p = 0.78).

There is significant difference in the distribution of PD subtypes in relation to ICD symptoms with TD subtype being the most predominant (x² 5.78; p = 0.056). Occurrence of ICD symptoms did not vary significantly across the different drug regimen for PD (x² 12.59; p = 0.127). There is significant association of PD duration with occurrence of ICD symptoms; the longer the PD duration, the higher the risk of developing ICD symptoms (x² 20.41; p = 0.026). Association of risk factors with individual ICD symptoms (Gender, PD subtype and PD meds) did not have any significant results except in PD meds vs. gambling (Table 1).

Analysis of the relationship of risk factors to occurrence of ICD symptoms did not produce any homogenous conclusive results when the entire population was taken into account. There is a significant association of PD duration and DDS (x2 22.79; p = 0.012) (Table 2). Longer duration of PD likely predisposes to the development of DDS.

Independent sample T test was used to demonstrate the association of mean H&Y stage with occurrence of ICD symptoms. Patients with higher mean modified Hoehn and Yahr stage (2.66±0.94), t 2.735, df 64, p 0.008, have much higher incidence of ICD symptoms (Table 4).

In this study, the prevalence of ICDs among adult Filipino patients with idiopathic PD was 24.2 % (16 out of 66 subjects). This was determined by using the QUIP-RS, a validated tool for detection of ICDs in PD patients¹². This is higher than the reported prevalence of 6 to 18.4% in Western studies and 7% in Chinese PD subjects. This diverse prevalence may be explained by type of anti-parkinsonian treatment, cultural, ethnic, social, and environmental differences⁷.

Recognizing the occurrence impulse control disorders among PD patients is significant because these behaviours may contribute to further impairment in the patient’s overall quality of life. They may also cause distress among their caregivers and have social and financial consequences, as well.

According to Weintraub, (2010), patients in dopamine agonist therapy have 2 to 3.5 fold-increased odds of developing ICDs. There is an association of higher levodopa dosages with ICDs in contrast with dopamine agonists¹³. The possible neurobiological mechanism for this association lies in the understanding of the interaction of these drugs with the dopamine receptors in the brain. Dopamine 1 and 2 (D1 & D2) receptors which are mostly confined in the dorsal striatum are responsible for the effects of dopamine therapy on motor symptoms. On the other hand, dopamine 3 (D3) receptors which are predominant in the ventral striatum of the brain are associated with behavioural addictions and substance abuse disorders¹⁴. Non-ergot dopamine agonists have relative affinity for D3 receptors. The active metabolite of levodopa which is dopamine shows higher affinity for D1 and D2 receptors¹³.

A study among Asian Parkinson disease patients by Lim, S. (2011) showed multiple demographic factors associated with ICD symptoms which include the following: male gender, longer disease duration, younger onset, dopamine agonist therapy, higher total levodopa equivalent units and higher dopamine agonist-only levodopa equivalent units. Eating, hypersexuality, hobbyism/ punding were prevalent while gambling and DDS were less frequent¹⁵.

In the data we have gathered, 7 patients with ICDs are on pure levodopa + carbidopa therapy, 6 patients on dual therapy of levodopa + carbidopa and anticholinergics, 2 patients on combination of levodopa + carbidopa, dopamine agonists and anticholinergics, and only 1 patient on levodopa + carbidopa plus dopamine agonist. The fact that most patients were on levopoda + carbidopa treatment is due to the low socioeconomic status of most patients seen at our outpatient department. Compulsive eating (50%) and hobbyism / punding (56.52%) are the common ICD symptoms in contrast to patients in developed countries such as the United States where compulsive gambling and shopping are prevalent¹³. This may be due to cultural differences and economic profile of our subjects, as well.

There is higher risk of developing ICD symptoms with longer duration of Parkinson disease (x² 20.41; p = 0.026) which is in keeping with the results garnered from other studies. With regard to PD subtype, most of the patients with ICDs had tremor dominant PD (x² 5.78; p = 0.056). We are able to show that a higher mean Modified Hoehn and Yahr stage correlates with development of ICD symptoms among our subjects (2.66±0.94), t 2.735, df 64, p 0.008.

Current management of ICD symptoms remains a challenge because it entails modifying dopaminergic therapy specifically the use of dopamine receptor agonists. There are no reported evidence for using psychiatric medications to address for these disabling behavioral conditions.

Filipino patients with idiopathic Parkinson disease who are majority on levodopa + carbidopa therapy may develop impluse control disorders (ICDs). Other contributory factors in development of ICDs include longer duration of PD and higher mean Modified Hoehn and Yahr stage.

The limitations of the study are as follow: small sample size, lack of matched controls, and that we did not correlate levodopa equivalent doses in the medications. Future research recommendation would include proper management of ICD symptoms and its complications.

We are grateful to Dr. Daniel Weintraub for allowing us to use the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease-Rating Scale (QUIP-RS) in this study and to Dr. Ramon Miguel Molina for his assistance in the statistical analysis.

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