Advanced therapies in Parkinson's disease: an individualized approach to their indication.

Device aided therapies (DAT) comprising the intrajejunal administration of levodopa/carbidopa intestinal gel (LCIG) and levodopa/carbidopa/entacapone intestinal gel (LECIG), the continuous subcutaneous application of foslevodopa/foscarbidopa or apomorphine infusion (CSAI) and deep brain stimulation (DBS) are used to treat Parkinson's disease with insufficient symptom alleviation under intensified pharmacotherapy. These DAT significantly differ in their efficacy profiles, indication, invasiveness, contraindications, and potential side effects. Usually, the evaluation of all these procedures is conducted simultaneously at the same point in time. However, as disease progression and symptom burden is extremely heterogeneous, clinical experience shows that patients reach the individual milestones for a certain therapy at different points in their disease course. Therefore, advocating for an individualized therapy evaluation for each DAT, requiring an ongoing evaluation. This necessitates that, during each consultation, the current symptomatology should be analyzed, and the potential suitability for a DAT be assessed. This work represents a critical interdisciplinary appraisal of these therapies in terms of their individual profiles and compares these DAT regarding contraindications, periprocedural considerations as well as their efficacy regarding motor- and non-motor deficits, supporting a personalized approach.

Tools and criteria to select patients with advanced Parkinson's disease for device-aided therapies: a narrative review.

This article provides an overview of the various screening and selection tools which have been developed over the past 25 years to identify patients with Parkinson's disease (PD) possibly eligible for device-aided therapies (DATs). For the available screening tools, we describe the target therapies (subtypes of DAT), development methods, validation data, and their use in clinical practice. In addition, the historical background and potential utility of these screening tools are discussed. The challenges in developing and validating these tools are also addressed, taking into account the differences in population, the local health care organization, and resource availability.

Non-oral continuous drug delivery based therapies and sleep dysfunction in Parkinson's disease.

Continuous drug delivery (CDD) has emerged as a feasible and pragmatic therapeutic option for dopamine replacement therapy in advanced Parkinson's disease (PD). CDD aims to mimic the physiological tonic dopamine release from striatal dopaminergic neurons and thus reduces the severity and duration of motor and non-motor fluctuations partly related to pulsatile levodopa stimulation. Non-motor symptoms and fluctuations are ubiquitous in PD and include sleep dysfunction, a problem that occurs in over 90% of PD patients across all stages, from prodromal to palliative. In this review, we discuss the currently available and in development non-oral dopaminergic CDD strategies with a focus on their efficacy in the treatment of the burdensome sleep dysfunction in PD.

Gut microbiota and metabolome distinctive features in Parkinson disease: Focus on levodopa and levodopa-carbidopa intrajejunal gel.

BACKGROUND AND PURPOSE: Recent data suggest that imbalances in the composition of the gut microbiota (GM) could exacerbate the progression of Parkinson disease (PD). The effects of levodopa (LD) have been poorly assessed, and those of LD-carbidopa intestinal gel (LCIG) have not been evaluated so far. The aim of this study was to identify the effect of LD and LCIG, in particular, on the GM and metabolome. METHODS: Fecal DNA samples from 107 patients with a clinical diagnosis of PD were analyzed by next-generation sequencing of the V3 and V4 regions of the 16S rRNA gene. PD patients were classified in different groups: patients on LCIG (LCIG group, n = 38) and on LD (LD group, n = 46). We also included a group of patients (n = 23) without antiparkinsonian medicaments (Naïve group). Fecal metabolic extracts were evaluated by gas chromatography mass spectrometry. RESULTS: The multivariate analysis showed a significantly higher abundance in the LCIG group of Enterobacteriaceae, Escherichia, and Serratia compared to the LD group. Compared to the Naïve group, the univariate analysis showed a reduction of Blautia and Lachnospirae in the LD group. Moreover, an increase of Proteobacteria, Enterobacteriaceae, and a reduction of Firmicutes, Lachnospiraceae, and Blautia was found in the LCIG group. No significant difference was found in the multivariate analysis of these comparisons. The LD group and LCIG group were associated with a metabolic profile linked to gut inflammation. CONCLUSIONS: Our results suggest that LD, and mostly LCIG, might significantly influence the microbiota composition and host/bacteria metabolism, acting as stressors in precipitating a specific inflammatory intestinal microenvironment, potentially related to the PD state and progression.

Comprehensive assessment of levodopa-carbidopa intestinal gel for Turkish advanced Parkinson's disease patients

Background/aim: Levodopa-carbidopa intestinal gel (LCIG) is an effective treatment modality in the management of advanced Parkinson's disease (PD) despite frequent adverse events and different rates of dropouts. Efficacy and safety data regarding Turkish patients on LCIG are limited. This study aims to report in detail the efficacy and adverse effect profile of LCIG among advanced PD patients from a Turkish center for movement disorders. Materials and methods: Twenty-two patients (50% male) who started receiving LCIG between December 2014 and March 2020 were recruited. The efficacy of LCIG was assessed with the Unified Parkinson's Disease Rating Scale (UPDRS III), Clinical Global Improvement (CGI) scale, and Quality of Life scale (PDQ8). Improvements in gait disorders and nonmotor features were also questioned. Adverse events (AE) were collated into 3 topics: related to percutaneous endoscopic gastrojejunostomy (PEG-J), device-related, and LCIG infusion-related. Results: Mean age and pre-LCIG disease duration were 66.7 (8.8) and 13.3 (8.0) years respectively. UPDRS III scores and H-Y scale assessments significantly improved. Better quality of life scores, clinical global improvements, and improvements in dysarthria, dysphagia, and gait were observed. None of our patients dropped out or died during a mean 17.5-month (12.3) period. Overall 20 (90.9%) patients experienced at least one AE. Twelve patients had PEG-J­related complications; three had acute abdomen. Eight (36.4%) patients had device-associated problems. Half of the patients required at least one additional endoscopic procedure and 7 had a device replaced. Mean body weight decreased from 69.5 to 62.5 kg and seven patients had newly onset PNP at a follow-up electromyography. Dyskinesia related to LCIG infusion was observed in 5 (22.7%) patients. There was no significant increase in hallucination among patients. Conclusion: LCIG is an efficient treatment modality in the management of Turkish patients with advanced Parkinson's disease. Although most of the patients had at least one AE, none of them dropped out. Patient selection, patient compliance, and collaborative management are important steps affecting the success of modality.

Levodopa-responsive retrocollis on the background of choreic dyskinesia.

Purpose/aim: Retrocollis can substantially disturb the daily living of individuals with Parkinson's disease (PD). Clinician often encounter the difficulty in managing the retrocollis. Materials and Methods: We describe a patient with PD who presented with choreic dyskinesia and levodopa-responsive retrocollis. Results: The patient had dyskinesia and the off periods, and received levodopa (700 mg, 14 times/day). The patient received levodopa-carbidopa intestinal gel (LCIG) treatment. After several months, the patient complained of difficulty in swallowing and speech due to severe retrocollis. Thirty minutes following a fast levodopa infusion of LCIG, the retrocollis improved. As a result, a frontal view was obtained, and her talking abilities showed improvement. Conclusions: Severe retrocollis can be superimposed on choreic dyskinesia, and it was likely to increase during the off periods. Duodenal levodopa infusion may reduce the severity of retrocollis.

Dynamics of device-based treatments for Parkinson's disease in Germany from 2010 to 2017: application of continuous subcutaneous apomorphine, levodopa-carbidopa intestinal gel, and deep brain stimulation.

Parkinson's disease (PD) is a very common extrapyramidal movement disorder and currently the world's fastest growing neurological disorder. In the course of disease progression, a majority of PD patients develop severe motor fluctuations which often cannot be adequately treated with common oral anti-Parkinsonian medications. With continuous subcutaneous apomorphine infusion (CSAI), levodopa-carbidopa intestinal gel infusion (LCIG), and deep brain stimulation (DBS), there exist three effective treatment options for advanced PD patients with motor fluctuations. In this study, we analyze the dynamics of implementation for these treatments in Germany over the years 2010-2017 based on the diagnosis-related group statistics and structured quality reports. All three intensified therapy measures are increasingly applied in Germany. The mean age of therapy implementation is rising and more male than female patients receive treatments. Although DBS is provided primarily in university hospitals with a caseload of at least two procedures per month, there exists a substantial proportion of DBS procedures which is conducted in hospitals with only a low caseload. Most of the drug pump implementations (CSAI and LCIG) are conducted in a large number of hospitals with an overall low case number. As we detect a strong rise of the implementation of these device-based therapies, it will be a challenging task to satisfy patient need and perpetuate high standards for these specialized procedures in the future.

Levodopa-carbidopa intestinal gel: 'dismantling the road blocks of a journey'.

Levodopa-carbidopa intestinal gel offers superior treatment to standard oral therapy in selective patients with advanced Parkinson disease. The costs involved in instituting and maintaining this treatment are high but largely mitigated with the quality of life years the treatment offers. Key to this is ensuring a high retention rate once the treatment is instituted. We outline factors and considerations from our experience and viewpoints at each stage of the process to address in this 'journey' patients undertake that can help maximise retention rates and benefits.

The effect of levodopa-carbidopa intestinal gel infusion long-term therapy on motor complications in advanced Parkinson's disease: a multicenter Romanian experience.

Chronic treatment with oral levodopa is associated with an increased frequency of motor complications in the late stages of Parkinson's disease (PD). Continuous administration of levodopa-carbidopa intestinal gel (LCIG-Duodopa(®), Abbott Laboratories), which has been available in Romania since 2009, represents an option for treating patients with advanced PD. Our primary objective was to report changes in motor complications after initiation of LCIG therapy. The secondary objectives were as follows: to determine the impact of LCIG therapy on the daily levodopa dose variation before/and after LCIG, to collect patient self-assessments of quality of life (QoL), and to study the overall tolerability and safety of LCIG administration. A retrospective analysis (2009-2013) of LCIG therapy and the experience in nine neurology centers in Romania was performed. The impact of LCIG therapy was evaluated by analyzing changes in motor fluctuations, dyskinesia and the patients' QoL after initiating therapy. The safety of LCIG therapy was estimated by noting agent-related adverse events (AEs) and medical device-related AEs. In the 113 patients included, we observed a significant improvement in PD symptoms after initiation of LCIG therapy. The "on" period increased, with a mean value of 6.14 h, and the dyskinesia period was reduced, with a mean value of 29.4 %. The quantified non-motor symptoms subsided. The patients exhibited significant improvements in QoL scores. There were few AEs and few cases of LCIG therapy discontinuation. LCIG is an important and available therapeutic option for managing patients with advanced PD.

Determination of the motor status of patients with advanced Parkinson's disease under levodopa-carbidopa intestinal gel using a machine learning model.

BACKGROUND: Despite the careful selection of candidate patients, the levodopa-carbidopa intestinal gel (LCIG) treatment of advanced Parkinson's disease (PD) remains challenging due to a complex interplay between motor and non-motor symptoms. We developed a random forest (RF) model to determine the postoperative motor outcome of patients with advanced PD at 2 years under the LCIG therapy by using motor and non-motor data from a Greek multicenter, observational registry (ForHealth S.A.). METHODS: This was a prospective 24-month, observational study of 59 patients with advanced PD under LCIG treatment from September 2019 to September 2021. Motor status was assessed with the Unified Parkinson's Disease Rating Scale (UPDRS) parts III and IV. Non-motor symptoms (NMS) were assessed by the Non-Motor Symptoms Questionnaire (NMSQ) and the Geriatric Depression Scale (GDS). RESULTS: We demonstrated that the proper combination of motor and non-motor measures significantly determines the motor outcome (UPDRS-III year 2: 23.57 ± 14.22 p < 0.001), reducing the RMSE (root-mean-square-error) from 3.487279 to 3.066292, suggesting that the optimized model performed well. Based on the "IncNodePurity," the major determinant factors of UPDRS-III (year 2) were, in descending order: UPDRS-III (year 0), disease duration, NMSQ (year 2), age, NMSQ (year 0), time off (hours) (year 2), time dyskinesia (year 0), quality of life (year 2) after the LCIG implementation. CONCLUSIONS: The novelty of this model is the possibility to determine the motor outcome after two years of LCIG. This model could be also useful for not specialized Parkinson's neurologists, to improve patient counseling, expectation management, and patient satisfaction with LCIG therapy.

The impact of dysphagia in Parkinson's disease patients treated with levodopa/carbidopa intestinal gel.

BACKGROUND: Dysphagia is common in advanced phases of Parkinson disease (PD), and is a risk factor for aspiration pneumonia. Nonetheless, dysphagia has been poorly investigated in PD patients treated with levodopa-carbidopa intestinal gel (LCIG). We aimed to analyze the impact of dysphagia on mortality in LCIG treated patients and its relationship with other PD disability milestones. METHODS: We retrospectively evaluated 95 consecutive PD patients treated with LCIG. Kaplan-Meier and log-rank test were used to compare mortality in patients with dysphagia from others. Cox regression was used to estimate the impact of dysphagia, age, disease duration, and Hoehn and Yahr (H&Y) on mortality in the entire cohort. Finally, univariate and multivariate regression analyses were used to estimate the association between dysphagia and age, disease duration, H&Y, hallucinations, and dementia. RESULTS: A significantly higher mortality rate was observed in patients with dysphagia. In the Cox model, dysphagia was the only feature significantly associated with mortality (95%CI 2.780-20.609; p < 0.001). Univariate analyses showed a significant correlation between dysphagia and dementia (OR: 0.387; p:0.033), hallucinations (OR: 0.283; p:0.009), and H&Y score (OR: 2.680; p < 0.001); in the multivariate analysis, only the H&Y stage was associated with the presence of dysphagia (OR: 2.357; p:0.003). CONCLUSION: Dysphagia significantly increased the risk of death in our cohort of LCIG-treated patients, independently from other relevant features such as age, disease duration, dementia, and hallucinations. These findings support the management of this symptom as a priority in the advanced PD stages, even in people treated with LCIG.

Levodopa/carbidopa intestinal gel via percutaneous endoscopic transgastric jejunostomy in advanced Parkinson's disease: hitting two birds with one stone?

Here we focus on people with advanced PD undergoing percutaneous endoscopic transgastric jejunostomy (PEG-J) ("one stone") for LCIG infusion therapy for managing severe motor fluctuations ("first bird") and discuss its implications for improving accompanying symptoms of cardiovascular, urinary, and gastrointestinal autonomic failure ("second bird").

Impact of Intestinal Bacteria on Levodopa Pharmacokinetics in LCIG Therapy.

Background: Levodopa-carbidopa intestinal gel (LCIG) therapy is used in advanced Parkinson's disease (PD) and consists of continuous administration of levodopa directly into the jejunum through a percutaneous endoscopic gastro-jejunal (PEG-J) tube. Recently, the metabolism of levodopa by Enterococcus faecalis (E. faecalis) has been reported. Intestinal bacteria can also affect this therapy. Objectives: To investigate intestinal bacteria and examine its impact on levodopa blood concentration in patients with PD receiving LCIG therapy. Methods: We enrolled 6 patients receiving LCIG therapy in our department. After PEG-J tube replacement, intestinal bacteria were collected from the tip of the tube and were identified using culture and polymerase chain reaction (PCR) tests. Moreover, the presence of tyrosine decarboxylase, which metabolizes levodopa, was also confirmed by PCR test. The ability of these bacteria to metabolize levodopa was confirmed in vitro. Levodopa blood concentrations were also examined before PEG-J tube replacement. Results: Bacteria were detected in all 6 patients. E. faecalis was present in 4 patients. Moreover, tyrosine decarboxylase was detected in 2 patients. The identified bacteria displayed in vitro metabolization to dopamine in the 4 E. faecalis positive samples. The addition of carbidopa did not inhibit the metabolism of levodopa. However, there was no difference in the mean blood concentration of levodopa, regardless of the presence of E. faecalis. Conclusions: We found bacteria, including E. faecalis in the PEG-J tube. We observed levodopa metabolism in vitro, but there was no association with levodopa blood concentration. The effect of intestinal bacteria may be limited in patients receiving LCIG therapy.

Single-Center Study of 103 Consecutive Parkinson's Disease Patients with Levodopa-Carbidopa Intestinal Gel.

BACKGROUND: Levodopa-carbidopa intestinal gel (LCIG) effectively reduces off time and dyskinesia and increases on time in advanced Parkinson's disease (PD). However, patients with LCIG-infusion experience frequent complications and some discontinue treatment early on. OBJECTIVES: The objectives of this study were to find predictive factors for early dropout from the LCIG infusion, analyze the treatment burden on the tertiary health care system, and explore changes in medication during the LCIG treatment. METHODS: LCIG-infusion was administrated to 103 patients between July 2006 and May 2020 at the Helsinki University Hospital, accumulating 350 years of follow-up data. We evaluated, retrospectively, changes in medication during treatment, discontinuation of the infusion, and adverse events from the patient records. RESULTS: Living alone was a predictive factor for early dropout (OR = 3.88; 95% CI = 1.03-14.66; P = 0.045). The treatment burden on the tertiary health care system increased after the initiation of LCIG infusion mostly because of common complications related to the infusion system (median change of in- and out-patient visits +1, P = 0.03). Mean levodopa equivalent daily dose (LEDD) rose from baseline to 6 months (1246.7 vs. 1684.9, P = 0.001) and stabilized thereafter. Patients commonly switched from "polypharmacy" to "LCIG-only" or "LCIG + oral levodopa" medication-groups during long-term treatment. CONCLUSIONS: Recurrent complications related to the infusion system increase the treatment burden on tertiary healthcare system after the initiation of LCIG-infusion. Most patients continue long-term with the infusion. Few patients discontinue infusion during the first year after initiation and living alone appears to be a risk factor for this outcome.

Levodopa-Carbidopa Intestinal Gel may improve treatment-resistant freezing of gait in Parkinson's disease.

Introduction: Freezing of gait (FOG) is a highly disabling symptom in Parkinson's Disease (PD) with varying degree of benefits from oral dopaminergic medications and several subtypes that present with different medication states (e.g., off FOG, on FOG, pseudo-on FOG, supra-on FOG). Levodopa-Carbidopa Intestinal Gel (LCIG) greately reduces the variability of cerebral dopamine replacement inherent to oral therapies by continuous levodopa intestinal infusion. While LCIG may be superior to oral therapy in its ability to treat motor fluctuations and minimize off-time, there is no consensus regarding the overall effectiveness of LCIG specifically for the treatment of FOG in PD patients. Methods: A systematic literature review was conducted to understand the efficacy of LCIG to treat FOG in PD patients. A PubMed search was conducted using the search query "Intestinal AND (Levodopa OR L-dopa) AND Freezing of Gait AND Parkinson." Additional eligibility criteria included articles written in English and currently published journal articles. Articles were excluded if they did not have a clinical design or if they did not yield reportable data on FOG. Results: The literature search yielded 16 articles, of which 10 articles were included. Of the 10 studies included, there were 3 retrospective studies, 6 case reports or case series, and 1 open-label study. (n = 449 patients total and 318 FOG patients). Nine of the 10 studies concluded that LCIG has a favorable effect on FOG, though the metrics to evaluate benefits of LCIG on FOG varied among the articles. Conclusion: LCIG may be an effective treatment for PD patients suffering from FOG including those with poor response to oral medication, likely because of its ability to maintain steadier dopamine levels. Further research is necessary on LCIG as a therapy for refractory FOG, with particular attention to the different subtypes of FOG.

Vitamin B6 Deficiency Anemia Attributed to Levodopa/Carbidopa Intestinal Gel Therapy for Parkinson's Disease: A Diagnostic Pitfall for Myelodysplastic Syndrome with Ring Sideroblasts.

Vitamin B6 (VB6) is essential to heme synthesis, and its deficiency can lead to anemia. VB6 deficiency anemia is typically microcytic, hypochromic, and sideroblastic. VB6 deficiency is a well-recognized complication of levodopa/carbidopa therapy, as metabolism of levodopa to dopamine is VB6-dependent, and carbidopa irreversibly forms bonds and deactivates VB6. We herein report a 75-year-old man with advanced Parkinson's disease who developed severe VB6 deficiency anemia due to levodopa/carbidopa intestinal gel therapy. His anemia was promptly resolved with simple oral supplementation of pyridoxal phosphate hydrate. VB6 deficiency anemia can mimic myelodysplastic syndrome and thus is an important differential diagnosis for patients administered levodopa/carbidopa.

Management of Psychotic Symptoms in a Patient With Parkinson's Disease Maintained on Levodopa-Carbidopa Intestinal Gel by Paliperidone Long-Acting Injection: A Case Report.

This case presents a 47-year-old man, without known past psychiatric history who developed psychotic symptoms including delusions of infidelity and had homicidal plans against his wife after 10 months of Levodopa-Carbidopa intestinal gel insertion (LCIG). The patient was diagnosed with Parkinson's disease at age 34, which is being managed with LCIG. Patient Parkinson's symptoms were not well controlled with other pharmacological and surgical interventions tried previously. Despite the current guidelines in treating Parkinson's disease psychosis, the treating teams have faced many difficulties with the management of this patient's psychotic symptoms. After trying Risperidone Consta on August 24, 2018, the patient improved gradually, then he was shifted to Paliperidone long-acting injection (LAI) on September 12, 2018. One month later, the patient was seen in the outpatient department with much improvement in Paliperidone LAI. Reporting this case as the patient was seen on November 29, 2021, the patient is stable and doing well overall in terms of absent psychotic symptoms with minimal resting tremors. The success story of using LAIs such as our patient's response to Paliperidone LAI can help other psychiatrists expand their treatment options when facing such difficulties.

Motor and nonmotor symptoms in patients treated with 24-hour daily levodopa-carbidopa intestinal gel infusion: Analysis of the COmedication Study assessing Mono- and cOmbination therapy with levodopa-carbidopa inteStinal gel (COSMOS).

INTRODUCTION: Patients with advanced Parkinson's disease (APD) commonly experience motor and nonmotor symptoms (NMS) associated with functional limitations and decreased quality of life. We compared motor and nonmotor outcomes in patients with APD receiving 24- versus 16-h levodopa-carbidopa intestinal gel (LCIG). METHODS: Data from COSMOS, a large, real-world, retrospective and cross-sectional, observational study on LCIG and comedication in APD were obtained from medical records and a single patient visit for patients receiving 24- and 16-h LCIG infusion. Changes from baseline were evaluated for motor symptoms, NMS, and clinical characteristics. Safety was also assessed. RESULTS: Data for 401 patients were included in this subanalysis. At the patient visit there were 35 patients on 24-h LCIG and 366 on 16-h LCIG. "Off" time and dyskinesia (duration and severity) were reduced in both groups. In both LCIG treatment groups, prevalence of most symptoms was reduced. There were significant differences in the change from baseline in severity and frequency of freezing of gait with 24-h LCIG versus 16-h LCIG (p = 0.011 and p = 0.038), severity of urinary symptoms (p = 0.006), and frequency of cognitive impairment (p = 0.014) with 24-h LCIG versus 16-h LCIG. Adverse events were similar for both treatment groups and considered tolerable. CONCLUSIONS: LCIG 24-h infusion may be a useful treatment option, when clinically justified, for select patients with APD. CLINICAL TRIAL NUMBER: NCT03362879.

Comparative Effectiveness of Carbidopa-Levodopa Enteral Suspension and Deep Brain Stimulation on Parkinson's Disease-Related Pill Burden Reduction in Advanced Parkinson's Disease: A Retrospective Real-World Cohort Study.

INTRODUCTION: In advanced Parkinson's disease (PD), a high pill burden is associated with poor compliance, reduced control of symptoms, and decreased quality of life. We assessed the impact of carbidopa-levodopa enteral suspension (CLES) and deep brain stimulation (DBS) on PD-related pill burden. METHODS: A retrospective cohort analysis was conducted in the IBM MarketScan and Medicare Supplemental databases. Patients with advanced PD, taking only PD medications, and initiating CLES or DBS between 9 January 2015 and 31 July 2019 were identified. CLES patients were matched to DBS patients in a 1:3 ratio based on a propensity score to balance patient characteristics. Pill burden was measured as a 30-day average number of PD-related pills per day and was captured monthly. Pill-free status was evaluated as the percentage of patients receiving CLES or DBS monotherapy. Descriptive statistics were used to compare pill counts and assess the proportion of patients on monotherapy at 6 and 12 months after initiating CLES or DBS. RESULTS: The cohorts included 34 CLES patients matched to 97 DBS patients. A significant reduction in PD-related pill burden was observed at 6 months after initiation of CLES or DBS (∆CLES: -5.62, p < 0.0001; ∆DBS: -1.48, p = 0.0022). PD-related pill burden reduction in CLES patients was significantly greater than in matched DBS patients at 6 months (∆: -4.14, p < 0.0001), which was sustained at 12 months after initiation. At 12 months, nearly three times more CLES patients were pill free than DBS patients (29.41% and 10.31%, respectively, p = 0.0123). CONCLUSIONS: Device-aided therapies such as CLES and DBS are effective in significantly reducing PD-related pill burden. Patients treated with CLES were more likely to achieve pill-free status than patients receiving DBS.