Antiparkinsonian Drugs Research Articles

Spending trends on neuropsychiatric drugs in Minas Gerais, Brazil: is the offer of anti-parkinson drugs increasing?

Neuropsychiatric drugs are used for a wide variety of neurological and psychiatric conditions. This article aims to analyze the trend and determinants of public expenditure of these medicines in Minas Gerais, from 2010 to 2017. Data from the Integrated Materials and Services Administration System (SIAD) database were used to estimate volumes of acquisition and expenditure. A breakdown analysis was performed, and the list of purchased drugs was reviewed, and the Drug Utilization technique (DU90%) applied concerning anti-Parkinson drugs. Annual expenditure dropped by 36%, from R$ 111.7 million in 2010 to R$ 40.9 million in 2017, and the determinant factors were the falling prices and volume, associated with changes in the drug mix, which favored the acquisition, on average, of more expensive products. Higher levels of expenditure for anti-Parkinson drugs stand out, however, with a significant change in the list purchased. This study contributed to a better understanding of public spending on neuropsychiatric drugs. A reduced volume can increase the risk of shortages. Regarding anti-Parkinson drugs, there is no evidence to suggest an increased supply to the population.

Antiparkinsonian drugs as potent contributors to nocturnal sleep in patients with Parkinson's disease.

ObjectiveTo clarify whether antiparkinsonian drugs contribute to nocturnal sleep disturbances in patients with Parkinson’s disease (PD).BackgroundAlthough the major antiparkinsonian drugs L-dopa and dopamine agonists (DAs) have been found to affect sleep, little is known about the effects of specific drugs on sleep in PD patients.MethodsThe study participants consisted of 112 PD patients (median age 72.5 years [inter-quartile range: IQR 65–79]; mean disease duration 8.44 years [standard deviation: 7.33]; median Hoehn and Yahr stage 3 [IQR 2–3.75]) taking one of three types of non-ergot extended-release DAs (rotigotine 32; pramipexole 44; ropinirole 36) with or without L-dopa (median daily total dosage of antiparkinsonian drugs 525.5 mg [IQR 376.25–658] levodopa equivalent dose [LED]). Participants were assessed using the PD Sleep Scale-2 (PDSS-2).ResultsFor the whole PD patient cohort, the PDSS-2 sleep disturbance domain score and the scores for item 1 assessing sleep quality and item 8 assessing nocturia were positively correlated with daily total dosage of antiparkinsonian drugs and dosage of L-dopa, but not with the dosage of DAs. Sub-analysis according to DA treatment revealed that DA dosage was not correlated with item 1 or 8 score in any of the subgroups. The LED ratio of rotigotine to the total dosage of antiparkinsonian drugs was inversely correlated with the item 1 score.ConclusionsThese data suggest that antiparkinsonian drugs, in particular L-dopa, adversely affect nocturnal sleep in PD patients, especially in terms of sleep quality and nocturia. Thus, adjusting both the total dosage of antiparkinsonian drugs and the dose-ratio of L-dopa might be key actions for alleviating poor sleep quality in patients with PD. Among DAs, we found a clear positive correlation between the dose-ratio of rotigotine and sleep quality. Thus, partial L-dopa replacement with rotigotine could improve sleep quality in patients with PD.

Competitive Adsorption of Anti-Parkinson Drugs on Different Amberlite Resins from Water: Quantitative Analysis by Ultra Performance Liquid Chromatography (UPLC)

Competitive Adsorption of Anti-Parkinson Drugs on Different Amberlite Resins from Water: Quantitative Analysis by Ultra Performance Liquid Chromatography (UPLC)

Structure‐Guided Design of G‐Protein‐Coupled Receptor Polypharmacology

AbstractMany diseases are polygenic and can only be treated efficiently with drugs that modulate multiple targets. However, rational design of compounds with multi‐target profiles is rarely pursued because it is considered too difficult, in particular if the drug must enter the central nervous system. Here, a structure‐based strategy to identify dual‐target ligands of G‐protein‐coupled receptors is presented. We use this approach to design compounds that both antagonize the A2A adenosine receptor and activate the D2 dopamine receptor, which have excellent potential as antiparkinson drugs. Atomic resolution models of the receptors guided generation of a chemical library with compounds designed to occupy orthosteric and secondary binding pockets in both targets. Structure‐based virtual screens identified ten compounds, of which three had affinity for both targets. One of these scaffolds was optimized to nanomolar dual‐target activity and showed the predicted pharmacodynamic effect in a rat model of Parkinsonism.

Structure-Guided Design of G-Protein-Coupled Receptor Polypharmacology.

Many diseases are polygenic and can only be treated efficiently with drugs that modulate multiple targets. However, rational design of compounds with multi‐target profiles is rarely pursued because it is considered too difficult, in particular if the drug must enter the central nervous system. Here, a structure‐based strategy to identify dual‐target ligands of G‐protein‐coupled receptors is presented. We use this approach to design compounds that both antagonize the A2A adenosine receptor and activate the D2 dopamine receptor, which have excellent potential as antiparkinson drugs. Atomic resolution models of the receptors guided generation of a chemical library with compounds designed to occupy orthosteric and secondary binding pockets in both targets. Structure‐based virtual screens identified ten compounds, of which three had affinity for both targets. One of these scaffolds was optimized to nanomolar dual‐target activity and showed the predicted pharmacodynamic effect in a rat model of Parkinsonism.

A Two Hour Synthesis of the Anti-Parkinson Drug Safinamide Methanesulfonate

AbstractThe critical moment of the COVID-19 outbreak requires a real-time supply of therapeutic agents. Thus, time economy in the synthesis of biologically active compounds has become increasingly decisive. In this work, we developed a two hour synthesis of the anti-Parkinson drug safinamide methanesulfonate in four steps with a 64% overall yield. Microwave irradiation was used in the first three steps in a one-pot fashion. In fact, the protocol can provide safinamide free base in one hour without a chromatographic purification step. Also, green solvents such as methanol and ethyl acetate are used.

Alpha-Synuclein as a Biomarker of Parkinson's Disease: Good, but Not Good Enough.

Parkinson’s disease (PD) is the second most common neurodegenerative disorder of the elderly, presenting primarily with symptoms of motor impairment. The disease is diagnosed most commonly by clinical examination with a great degree of accuracy in specialized centers. However, in some cases, non-classical presentations occur when it may be difficult to distinguish the disease from other types of degenerative or non-degenerative movement disorders with overlapping symptoms. The diagnostic difficulty may also arise in patients at the early stage of PD. Thus, a biomarker could help clinicians circumvent such problems and help them monitor the improvement in disease pathology during anti-parkinsonian drug trials. This review first provides a brief overview of PD, emphasizing, in the process, the important role of α-synuclein in the pathogenesis of the disease. Various attempts made by the researchers to develop imaging, genetic, and various biochemical biomarkers for PD are then briefly reviewed to point out the absence of a definitive biomarker for this disorder. In view of the overwhelming importance of α-synuclein in the pathogenesis, a detailed analysis is then made of various studies to establish the biomarker potential of this protein in PD; these studies measured total α-synuclein, oligomeric, and post-translationally modified forms of α-synuclein in cerebrospinal fluid, blood (plasma, serum, erythrocytes, and circulating neuron-specific extracellular vesicles) and saliva in combination with certain other proteins. Multiple studies also examined the accumulation of α-synuclein in various forms in PD in the neural elements in the gut, submandibular glands, skin, and the retina. The measurements of the levels of certain forms of α-synuclein in some of these body fluids or their components or peripheral tissues hold a significant promise in establishing α-synuclein as a definitive biomarker for PD. However, many methodological issues related to detection and quantification of α-synuclein have to be resolved, and larger cross-sectional and follow-up studies with controls and patients of PD, parkinsonian disorders, and non-parkinsonian movement disorders are to be undertaken.

Development of a Hydrophobicity-Controlled Delivery System Containing Levodopa Methyl Ester Hydrochloride Loaded into a Mesoporous Silica.

Background: The drug release of antiparkinsonian drugs is an important issue during the formulation process because proper release kinetics can help to reduce the off periods of Parkinson’s disease. A 2-factor, 3-level (32) full-factorial design was conducted to evaluate statistically the influence of the hydrophobicity of mesoporous silica on drug release. Methods: Hydrophobization was evaluated by different methods, such as contact angle measurement, infrared spectroscopy and charge titration. After loading the drug (levodopa methyl ester hydrochloride, melevodopa hydrochloride, LDME) into the mesopores, drug content, particle size, specific surface area and homogeneity of the products were also analyzed. The amorphous state of LDME was verified by X-ray diffractometry and differential scanning calorimetry. Results: Drug release was characterized by a model-independent method using the so-called initial release rate parameter, as detailed in the article. The adaptability of this method was verified; the model fitted closely to the actual release results according to the similarity factor, independently of the release kinetics. Conclusions: The API was successfully loaded into the silica, resulting in a reduced surface area. The release studies indicated that the release rate significantly decreased (p < 0.05) with increasing hydrophobicity. The products with controlled release can reduce the off period frequency.

Preliminary Studies on Optimization of Anti-Parkinson Drug Loaded Lipid Nanoparticles Enriched Hydrogel Formulations for Management of Parkinson’s Disease

Introduction: Ropinirole (RP), is a selective dopamine agonist that is used alone or with other medications to treat the symptoms of Parkinson’s disease (PD). RP has low bioavailability of only about 50% due to the first-pass metabolism, and it requires frequent dosing during oral administration. Aim: The objective of the current research was to develop RP-loaded solid lipid nanoparticles (RP- SLNs), nanostructured lipid carriers (RP-NLCs), and their corresponding hydrogels (RP-SLN-C and RP-NLC-C) that could enhance RP therapeutic outcomes during PD treatment. Methods: RP nanoparticles were prepared by homogenization followed by probe sonication and optimized based on particle size, polydispersity index (PDI), zeta potential (ZP), % assay, % entrapment efficiency, and in vitro release studies. Optimized formulations were converted into hydrogel formulations using Carbopol 934 as a gelling polymer and optimized based on rheological and release characteristics. Optimized formulations were further evaluated using differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), scanning electron microscopy (SEM), freeze-drying, and stability study at refrigerated and room temperatures. Results: The optimized RP-SLN formulation showed particle size and entrapment efficiency of 213.5±3.8 nm and 77.9±3.1% compared to 190.6±3.7 nm and 85.7±1.7% for optimized RP-NLC formulation. PXRD supplemented and confirmed DSC results, RP was entrapped in a molecularly dispersed state inside the core of the lipid nanocarrier. Furthermore, RP-loaded lipid nanocarriers revealed a spherical shape in SEM images. In vitro release studies demonstrated sustained release profiles for RP from SLNs, NLCs, and their hydrogels over 24 h. Optimized SLN, NLC, and nanocarrier- loaded hydrogel formulations were stable over three months at 4ºC and 25ºC storage conditions. Conclusion: Overall, the results demonstrated that lipid nanocarriers and their corresponding hydrogel formulations can be considered as a topical drug delivery vehicle for RP during the treatment of PD.

Deep Brain Stimulation of Globus Pallidus

The globus pallidus internus(GPi)has evolved as a potential target for deep brain stimulation(DBS)in patients with advanced Parkinson's disease(PD). GPi stimulation has a significant impact on intractable hyperkinetic movement disorders. Optimal surgical procedures require a combination of image-based targeting and intraoperative microelectrode recording(MER)strategies. Provocation with stimulation through microelectrode or a DBS electrode is also crucial for refining the appropriate electrode position and obtaining a wide therapeutic window of stimulation parameters. In patients with PD, the best target for deep brain stimulation, whether subthalamic nucleus(STN)or the GPi, has been a subject of interest in recent medical literature. STN remains the preferred target for DBS in patients with advanced PD worldwide. In postoperative medication reduction, numerous data support that STN stimulation reduces the total dose of anti-parkinsonian drugs compared to GPi stimulation. However, GPi stimulation has shown a direct anti-dyskinetic effect, without reducing levodopa. Thus, GPi stimulation might be recommended for patients with neurocognitive or neuropsychiatric issues. GPi stimulation has a potential for treating hyperkinetic movement disorders. In patients with PD, STN stimulation is preferred worldwide; however, GPi stimulation has a clinical advantage only for select patients.

Analyses of Child and Youth Self-Poisoning Hospitalizations by Substance and Socioeconomic Status.

Child and youth self-poisoning is a growing public health issue in many regions of the world, including British Columbia (BC), Canada, where 15–19-year-olds have the highest rates of self-poisoning hospitalizations compared with those of all other ages. The purpose of this study was to identify what substances children and youth commonly used to poison themselves in BC and how socioeconomic status may impact self-poisoning risk. Self-poisoning hospitalization rates among 10–14 and 15–19-year-olds from 1 April 2012 to 31 March 2020 were calculated by substance using ICD-10-CA codes X60-X69 and T36-T65, as well as by socioeconomic status using the Institut National de Santé Publique du Québec’s Deprivation Index. Nonopioid analgesics, antipyretics, and antirheumatics were the most common substances involved, with rates of 27.6 and 74.3 per 100,000 population among 10–14 and 15–19-year-olds, respectively, followed by antiepileptic, sedative–hypnotic, antiparkinsonism, and psychotropic drugs, with rates of 20.2 and 68.1 per 100,000 population among 10–14 and 15–19-year-olds, respectively. In terms of socioeconomic status, rates were highest among 10–19-year-olds living in neighbourhoods with the fewest social connections (243.7 per 100,000 population). These findings can inform poisoning prevention strategies and relevant policies, thereby reducing the number of self-poisoning events among children and youth.

Multivariate optimization of a novel electrode film architecture containing gold nanoparticle-decorated activated charcoal for voltammetric determination of levodopa levels in pre-therapeutic phase of Parkinson`s disease

• Activated charcoal (AC) is a low cost alternative material for electroanalysis. • A robust modified electrode is developed by immobilizing gold nanoparticle-decorated activated charcoal (AuNPs-AC) film. • A Doehlert matrix design experiment is used to optimize the electrode performance. • The AuNPs-AC based sensor presents enhanced response toward an antiparkinsonian drug sensing • The voltammetric method was successfully applied for levodopa determination in biological and environmental samples. Levodopa analysis is important to monitor progress of patients in Parkinson's disease, as well as to determine the treatment directions. In this way, the development of an electrochemical sensor based on a glassy carbon electrode modified with gold nanoparticles supported in activated charcoal with an epichlorohydrin-reticulated chitosan film was carried out under the assistance of a Doehlert matrix design experiment. The resulting electrode was subjected to a series of characterization techniques, including scanning electron microscopy, transmission electron microscopy, and X-ray diffraction, for morphological analysis, as well as electrochemical impedance spectroscopy and cyclic voltammetry for electrochemical characterization. The active surface presented response for electrocatalytic oxidation of levodopa with high current response at reduced potential, which was applied, along with a square-wave adsorptive anodic stripping voltammetric methodology, for analysis of levodopa in different samples, presenting a three order of magnitude linear concentration range (50.0 nmol L −1 to 10.0 µmol L −1 ), low detection limit of 8.2 nmol L −1 , good recovery analysis of spiked samples with low signal deviation under the presence of interfering species, and good accuracy front a comparative methodology. Schematic representation of experimental steps followed for determination of levodopa levels in pre-therapeutic phase of Parkinson`s disease by a square-wave adsorptive anodic stripping voltammetric method.

Profile and frequency of antiparkinsonian drugs adverse reactions: a systematic review and meta-analysis

Objective: to assess the predictors and prevalence of adverse drug reactions (ADRs) associated with antiparkinsonian drugs.Materials and methods. 18 clinical studies and randomized controlled trials were included in the analysis. We combined all registered ADRs for each drug and made direct comparisons with odds ratio (OR) and 95% confidence interval (95% CI) calculation.Results and discussion. Levodopa/benserazide (LB) had the best safety profile among levodopa drugs. Levodopa/carbidopa (LC) compared with LB was associated with more frequent development of nausea (OR=2.8; 95% CI: 1.51–5.21), aggravation of parkinsonism (OR=4.44; 95% CI: 2.12–9.28) and dizziness (OR=3.32; 95% CI: 1.5–7.33; p=0.002). Piribedil had the lowest number of ADRs among dopamine receptor agonists. Dizziness was more common with pramipexole and ropinirole than with levodopa (OR=1.82; 95% CI: 1.21–2.74 and OR=1.65; 95% CI: 1.11–2.44 respectively). Increased daytime sleepiness and peripheral edema have also been associated with pramipexole. Arterial hypertension was present in 9.6% of patients prescribed with piribedil. Amantadine compared with pramipexole was associated with a higher risk of hallucinations (OR=2.27; 95% CI: 1.24–4.12) and constipation (OR=2.40; 95% CI: 1.14–5.05). Patients prescribed with selegeline had higher odds of dizziness (OR=3.40; 95% CI: 1.76–6.55) and hallucinations (OR=4.30; 95% CI: 1.83–10.09) compared to rasagiline.Conclusion. Based on the results, we propose a diagram of the relationship between ADRs and their frequency with antiparkinsonian drugs. We hope that the study will find clinical application and allow neurologists to consider the effectiveness and the expected risks of ADRs in the treatment of PD.

Gamma-decanolactone: Preliminary evaluation as potential antiparkinsonian drug

Treatment of Parkinson's disease (PD) includes the use of monoamine oxidase-B (MAO-B) inhibitor drugs. In this work we have evaluated the possible gamma-decanolactone (GD) effect in vitro to inhibit the A and B isoforms of human monoamine oxidase (hMAO) enzyme and their citotoxicity in human hepatoma cell line (HepG2). Also, binding studies to A1, A2A A2B and A3 adenosine receptors were performed.A docking study of gamma-decanolactone has been carried out with the molecular targets of MAO-A and MAO-B isoforms.The physicochemical properties and ability to cross physiological barriers, as the blood brain barrier (BBB), was elucidated by computational studies.The in vivo assays, the rota-rod test, body temperature assessment and open field test were performed in reserpinized mice (1.5 mg/kg, i.p.; 18:00 before) to evaluate the effect of gamma-decanolactone (300 mg/kg), alone or associated with Levodopa plus Benserazide (LD + BZ, 100:25 mg/kg, i.p.).Gamma-decanolactone inhibited preferentially the MAO-B in a reversible manner, with an inhibitory concentration of 50% (IC50) 55.95 ± 9.06 μM. It was shown to be a safe drug since only at the highest concentration decreased the viability of HepG2 cells. It also does not bind to adenosine receptors investigated in this study.The molecular docking study show that the gamma-decanolactone ligand adopts a relatively compact conformation in the active site of hMAO-B, while we note an extended conformation of gamma-decanolactone ligand in the hMAO-A isoform.The physicochemical properties obtained, and the theoretical models utilized for the evaluation of ability to cross the BBB, predict a good gamma-decanolactone bioavailability and access to the central nervous system (CNS).In the in vivo studies, gamma-decanolactone partially reversed the ataxia of the reserpinized mice at 01:00 h and 01:30 h post-administration. Concomitant treatment of gamma-decanolactone with LD + BZ, at 01:30 h showed a potentiation of the reversibility of ataxia and facilitated the reversal of hypothermia caused by reserpine for all measured times (P <0.01 vs vehicle), except at 24:00 h, but not reversed the hypokinesia in the open field test.In summary, the results herein obtained and in conjunction with previous studies, suggest that gamma-decanolactone could be a drug with potential utility as antiparkinsonian drug.

Gastroparesis in Parkinson Disease: Pathophysiology, and Clinical Management.

Patients with Parkinson disease (PD) experience a range of non-motor symptoms, including gastrointestinal symptoms. These symptoms can be present in the prodromal phase of the disease. Recent advances in pathophysiology reveal that α-synuclein aggregates that form Lewy bodies and neurites, the hallmark of PD, are present in the enteric nervous system and may precede motor symptoms. Gastroparesis is one of the gastrointestinal involvements of PD and is characterized by delayed gastric emptying of solid food in the absence of mechanical obstruction. Gastroparesis has been reported in nearly 45% of PD. The cardinal symptoms include early satiety, postprandial fullness, nausea, and vomiting. The diagnosis requires an appropriate test to confirm delayed gastric emptying, such as gastric scintigraphy, or breath test. Gastroparesis can lead to malnutrition and impairment of quality of life. Moreover, it might interfere with the absorption of antiparkinsonian drugs. The treatment includes dietary modifications, and pharmacologic agents both to accelerate gastric emptying and relieve symptoms. Alternative treatments have been recently developed in the management of gastroparesis, and their use in patients with PD will be reported in this review.

ADL-dependent older adults were identified in medico-administrative databases

ObjectiveWe aimed to develop an algorithm for the identification of basic Activities of Daily Living (ADL)-dependency in health insurance databases. Study Design and SettingWe used the AMI (Aging Multidisciplinary Investigation) population-based cohort including both individual face-to-face assessment of ADL-dependency and merged health insurance data. The health insurance factors associated with ADL-dependency were identified using a LASSO logistic regression model in 1000 bootstrap samples. An external validation on a 1/97 representative sample of the French Health Insurance general population of Affiliates has been performed. ResultsAmong 995 participants of the AMI cohort aged ≥ 65y, 114 (11.5%) were ADL-dependent according to neuropsychologists individual assessments. The final algorithm developed included: age, sex, four drug classes (dopaminergic antiparkinson drugs, antidepressants, antidiabetic agents, lipid modifying agents), three type of medical devices (medical bed, patient lifter, incontinence equipment), four medical acts (GP's consultations at home, daily and non-daily nursing at home, transport by ambulance) and four long-term diseases (stroke, heart failure, coronary heart disease, Alzheimer and other dementia). Applying this algorithm, the estimated prevalence of ADL-dependency was 12.3% in AMI and 9.5% in the validation sample. ConclusionThis study proposes a useful algorithm to identify ADL-dependency in the health insurance data.

Zonisamide upregulates neuregulin-1 expression and enhances acetylcholine receptor clustering at the in vitro neuromuscular junction

Decreased acetylcholine receptor (AChR) clustering compromises signal transmission at the neuromuscular junction (NMJ) in myasthenia gravis, congenital myasthenic syndromes, and motor neuron diseases. Although the enhancement of AChR clustering at the NMJ is a promising therapeutic strategy for these maladies, no drug is currently available for this enhancement. We previously reported that zonisamide (ZNS), an anti-epileptic and anti-Parkinson's disease drug, enhances neurite elongation of the primary spinal motor neurons (SMNs). As nerve sprouting occurs to compensate for the loss of AChR clusters in human diseases, we examined the effects of ZNS on AChR clustering at the NMJ. To this end, we established a simple and quick co-culture system to reproducibly make in vitro NMJs using C2C12 myotubes and NSC34 motor neurons. ZNS at 1–20 μM enhanced the formation of AChR clusters dose-dependently in co-cultured C2C12 myotubes but not in agrin-treated single cultured C2C12 myotubes. We observed that molecules that conferred responsiveness to ZNS were not secreted into the co-culture medium. We found that 10 μM ZNS upregulated the expression of neuregulin-1 (Nrg1) in co-cultured cells but not in single cultured C2C12 myotubes or single cultured NSC34 motor neurons. In accordance with this observation, inhibition of the Nrg1/ErbB signaling pathways nullified the effect of 10 μM ZNS on the enhancement of AChR clustering in in vitro NMJs. Although agrin was not induced by 10 μM ZNS in co-cultured cells, anti-agrin antibody attenuated ZNS-mediated enhancement of AChR clustering. We conclude that ZNS enhances agrin-dependent AChR-clustering by upregulating the Nrg1/ErbB signaling pathways in the presence of NMJs.

Influence of Chitosan Thioglycolic Acid Conjugate in improving bioavailability of an Antiparkinson drug; Rasagiline Mesylate from transdermal patch

: Objective Parkinson Disease (PD) is a chronic disorder of central nervous system mainly affecting the motor systems. The drug of choice to treat PD is Rasagiline Mesylate (RM) and it belongs to BCS class III drug. The objective of the present study was preparation of transdermal drug delivery system for RM. Several permeation enhancers were screened to be included in the formulation. To achieve desired flux a new strategy was developed by including in-house prepared CTC to enhance the permeation of RM. Methods The CTC was prepared by reaction between Chitosan and Thioglycolicacid, characterized by determining physical properties and applying analytical tools. Seven permeation enhancers with different mechanisms were screened. The transdermal patches were prepared with chitosan along with permeation enhancer IPM, various proportions of CTC and evaluated for physical and permeation studies. The optimized transdermal patch was obtained by two factors and three responses to obtain the design space and further evaluated for pharmacokinetic studies. Results The results of the present study confirmed the formation of CTC, IPM was best permeation enhancer among all. The presence of CTC in the formulations significantly improved the permeation of RM to achieve desired steady state flux. The relative bioavailability of optimized transdermal patch was determined and it was observed that improved bioavailability as compared to marketed conventional tablets. Conclusion The study was concluded that CTC has significant influence on permeation enhancing ability of IPM.

PND41 Direct Medical Costs of Parkinson's Disease in JAPAN

Parkinson’s disease (PD) is a chronic neurodegenerative disorder that affects 150,000 people in Japan. The objective of this study was to evaluate the direct medical costs of PD in Japan based on real-world data. We performed a retrospective descriptive study using the administrative claims data from more than 400 hospitals provided by Medical Data Vision Co., Ltd. Patients who had at least one diagnosis of PD (ICD10 G20) were identified and PD-related outpatient and inpatient cost were summarized in relation to the Hoehn and Yahr (HY) severity scale. PD-related direct cost was defined as neurology outpatient visits and hospitalizations to manage PD, pneumonitis due to inhalation of food and vomit (J69.0), and fracture of femur (S72.0, S72.1). Between April 2008 and December 2018, 120,353 PD patients were identified, and 16% were diagnosed with the HY scale (1,405; 3,377; 8,107; 3,887; 2,590 for HY1 to HY5). Mean age was 74.6 ± 10.9, 46.5% were male, and the mean observation duration was 443 days. Mean monthly outpatient cost was increased by HY scale (JPY 22,762; 29,322; 45,804; 56,500; 57,164; 32,937 for HY1 to HY5 and overall, respectively). Anti-Parkinson drugs cost was 50% and 70% for HY1-2 and HY3-5, respectively. A total of 17,428 PD-related hospitalization events were identified, and incidence (0.20; 0.22; 0.57; 1.63; 2.57; 0.53 times per year) and duration (24.3; 22.9; 30.4; 36.4; 51.1; 36.3 days) were also increased by HY scale. The total cost of hospitalization related to PD by HY scale were JPY 985K; 940K; 1,176K; 1,398K; 1,727K; and for all PD patients was 1,379K, where two-thirds of costs were admission charges. Direct medical costs of PD in Japan were increased by the severity of disease.

REM sleep behaviour disorder in Parkinson's disease (Review).

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia defined by simple or complex abnormal movements occurring in REM state, instead of the physiological muscular atonia. RBD may be idiopathic, or secondary as in the case of Parkinson's disease (PD). Several studies have confirmed that idiopathic RBD may precede with several years the onset of the specific motor characteristics of PD. The high prevalence of RBD in PD (19-70%) may be explained by several common pathophysiological pathways, mainly related to the dopaminergic cell loss. RBD is also associated with several comorbidities, including cognitive impairment, hallucinations, dysautonomia, or daytime sleepiness. The gold standard investigation for the diagnosis and assessment of RBD is video polysomnography, but in clinical practice, the use of clinical scales and questionnaires is reasonable for the screening of this complex parasomnia. Management options include ensuring a safe environment for the patient and pharmacological treatment, incuding clonazepam, melatonin or certain antiparkinsonian drugs.