Antiparkinsonian Medication Research Articles

Evaluating the Use of Oral Anti-Parkinsonian Medication in Patients with Advanced Parkinson’s Disease Who Are Treated with Deep Brain Stimulation and Are Receiving Levodopa-Carbidopa Intestinal Gel: Study Design and Interim Results (4668)

Evaluating the Use of Oral Anti-Parkinsonian Medication in Patients with Advanced Parkinson’s Disease Who Are Treated with Deep Brain Stimulation and Are Receiving Levodopa-Carbidopa Intestinal Gel: Study Design and Interim Results (4668)

9-Methyl-\u03b2-carboline inhibits monoamine oxidase activity and stimulates the expression of neurotrophic factors by astrocytes

β-Carbolines (BC) are pyridoindoles, which can be found in various exogenous and endogenous sources. Recent studies revealed neurostimulative, neuroprotective, neuroregenerative and anti-inflammatory effects of 9-methyl-BC (9-Me-BC). Additionally, 9-me-BC increased neurite outgrowth of dopaminergic neurons independent of dopamine uptake into these neurons. In this study, the role of astrocytes in neurostimulative, neuroregenerative and neuroprotective properties of 9-me-BC was further explored.9-Me-BC exerted anti-proliferative effects without toxic properties in dopaminergic midbrain and cortical astrocyte cultures. The organic cation transporter (OCT) but not the dopamine transporter seem to mediate at least part the effect of 9-me-BC on astrocytes. Remarkably, 9-me-BC stimulated the gene expression of several important neurotrophic factors for dopaminergic neurons like Artn, Bdnf, Egln1, Tgfb2 and Ncam1. These factors are well known to stimulate neurite outgrowth and to show neuroprotective and neuroregenerative properties to dopaminergic neurons against various toxins. Further, we show that effect of 9-me-BC is mediated through phosphatidylinositol 3-kinase (PI3K) pathway. Additionally, 9-me-BC showed inhibitory properties to monoamine oxidase (MAO) activity with an IC50 value of 1 µM for MAO-A and of 15.5 µM for MAO-B. The inhibition of MAO by 9-me-BC might contribute to the observed increased dopamine content and anti-apoptotic properties in cell culture after 9-me-BC treatment in recent studies. Thus, 9-me-BC have a plethora of beneficial effects on dopaminergic neurons warranting its exploration as a new multimodal anti-parkinsonian medication.

Monoamine oxidase B rs1799836 G allele polymorphism is a risk factor for early development of levodopa-induced dyskinesia in Parkinson's disease.

BackgroundDopamine replacement therapy is an established treatment for motor symptoms of Parkinson's disease, but its long-term use is often limited by the eventual development of motor complications, including levodopa-induced dyskinesia. Genetic background, particularly polymorphisms of dopamine metabolism genes, may affect the occurrence of dyskinesia in Parkinson's disease patients.MethodsWe investigated polymorphisms of dopamine metabolism genes, including catechol-O-methyltransferase, monoamine oxidase B, dopamine beta-hydroxylasedopamine, dopamine receptors D1, D2, and D3, and dopamine transporter, in 110 patients with Parkinson's disease. Cox proportional hazards regression was used to detect associations between genotypes and levodopa-induced dyskinesia.ResultsMonoamine oxidase B rs1799836 was the only polymorphism correlated with risk of dyskinesia. Patients with an AG or GG genotype were more likely to have dyskinesia than those with an AA genotype (adjusted hazard ratio, 3.41; 95% confidence interval, 1.28–9.10). Also, Kaplan-Meier curves demonstrated that patients with an AG or GG genotype developed dyskinesia earlier than those with an AA genotype (log-rank test, p = .004).ConclusionsIn Parkinson's disease patients, the monoamine oxidase B rs1799836 G allele is associated with a greater likelihood of developing dyskinesia than the A allele, possibly due to its association with lower monoamine oxidase B activity in the brain. Thus, detection of monoamine oxidase B polymorphisms may be useful for determining the optimal dosing of antiparkinson medications.

Cardiovascular Adverse Events Reported in Placebo Arm of Randomized Controlled Trials in Parkinson's Disease.

Parkinson's disease and cardiovascular disease are highly prevalent conditions in the elderly. Evidence shows inconsistent findings regarding the association between Parkinson's disease and cardiovascular events. We sought to evaluate the proportion of cardiovascular adverse events among Parkinson's disease patients included in the placebo arm of randomized controlled trials. For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from inception to February 2017. Randomized, placebo-controlled trials in Parkinson's disease were included. The primary outcome was the proportion of major cardiovascular adverse events, defined as myocardial infarction, stroke, peripheral artery disease, and sudden death. A random-effects meta-analysis was performed to derive pooled estimates of the proportion of adverse events and corresponding 95% confidence intervals (CIs). 236 randomized controlled trials were included, 80% (n = 189; 14704 patients) of which reported data on cardiovascular adverse events. The pooled proportion of major cardiovascular events ranged from 0.00% to 0.06% and the proportion of all cardiovascular adverse events was 3.33% (95% CI: 2.14, 4.70%), and ranged from 1.71% in de novo Parkinson's disease patients to 4.56% in patients receiving levodopa as their only antiparkinsonian medication. The most common adverse events were hypertension and orthostatic hypotension. These results suggest that the proportion of major cardiovascular adverse events is low and that blood pressure abnormalities are the most frequent cardiovascular adverse event.

Responding to Regulatory Pressure About Nursing Home Abuse

Responding to Regulatory Pressure About Nursing Home Abuse

A Phase 2a Trial Investigating the Safety and Tolerability of the Novel Cortical Enhancer IRL752 in Parkinson's Disease Dementia

IRL752 is a novel small-molecule compound that acts to regioselectively enhance norepinephrine, dopamine, and acetylcholine neurotransmission in the cerebral cortex. The primary objective of the trial was to investigate the safety and tolerability of IRL752 in patients with Parkinson's disease and dementia. Patients with Parkinson's disease and dementia were randomized to IRL752 or placebo treatment (3:1 ratio) for 28 days. The study drug was given as an adjunct treatment to the patients' regular stable antiparkinsonian medication. Dosing was individually titrated for 14 days after which the dose was kept stable for an additional 14 days. A total of 32 patients were randomized to treatment, and 29 patients completed the 4-week treatment. Adverse events were generally mild and transient and were mostly reported during the dose titration phase. There were 2 serious adverse events, and none of them were related to the experimental treatment. The average dose achieved in the stable dose phase was 600 mg daily, yielding a 2-hour postdose plasma concentration of about 4 μM on day 28. Exploratory assessment of secondary outcomes indicated efficacy for symptoms and signs known to be poorly responsive to levodopa. IRL752 appears to be safe and well tolerated for a 4-week treatment in patients with Parkinson's disease and dementia. © 2020 International Parkinson and Movement Disorder Society.

Research advances on L-DOPA-induced dyskinesia: from animal models to human disease.

L-3,4-dihydroxyphenylalanine (L-DOPA) was introduced about half a century ago and is still the most effective medicine for the treatment of Parkinson's disease (PD). However, such chronic treatment eventually leads to L-DOPA-induced dyskinesia (LID) on the majority of PD patients. Besides L-DOPA, dopamine agonists are able to induce dyskinesia as well. So far no drug is yet claimed to effectively curb LID, and amantadine has only a modest benefit on LID patients. Thus, understanding the molecular mechanisms behind LID is urgently needed, and developing new antiparkinsonian medications with low dyskinesia potential is necessarily required. In the last decades, several animal models have been generated for these aims. 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-lesioned monkey models always considered as gold standard of PD studies are also applied well for the research of LID. Additionally, several rodent models were developed for such clinical needs. Of them, 6-hydroxydopamine (OHDA)-lesioned rats or mice exhibiting countable abnormal involuntary movements (AIMs) after L-DOPA treatments have becoming widely applicable tools for LID pathogenesis studies. Under investigating these models for years, multiple potential LID-associated genes and pathways have been innovatively identified, which largely advance the therapeutic and preventative strategies for the disease. In this review, we attempt to update the recent findings represented in LID animal models and trial studies, which may facilitate the mechanistic understanding, drug development, and clinical evaluation of this movement disorder.

Wearing-off Identification in Parkinson's Disease: The shapd-woq Study.

Objectives: To clarify the frequency of wearing-off phenomenon (WO) and the validity of the Chinese version of the 9-item wearing-off questionnaire (CWOQ-9) in WO identification in this large population.Methods: Parkinson's patients treated with antiparkinsonian medications were consecutively recruited into this observational, cross-sectional investigation. Patients completed the CWOQ-9 prior to the independent clinician assessment.Results: A total of 1,385 patients were included in the analysis. The mean age was 69.7 ± 9.5 years and the mean disease duration was 5.8 ± 4.7 years. Clinicians identified WO in 763 patients, with an overall prevalence of 55.1%. In patients within 1 year of disease duration, clinicians diagnosed WO in eight patients, with a percentage of 12.9%. With the disease progression, the WO frequency gradually increased to 76.2% in patients with 10–15 years of disease duration. Then, it slowly decreased at a longer disease duration. The occurrence of WO was closely associated with the disease duration, H&Y staging, and levodopa daily dose. CWOQ-9 identified 1,071 patients (1071/1398, 77.33%) that had WO-related symptoms. The mean CWOQ-9 score was 3.4 ± 1.6. CWOQ-9 corresponded with clinician assessments of WO in 734 of 763 cases; clinicians disagreed with the CWOQ-9 considering the presence of WO in 337 of 1,071 cases. The sensitivity and specificity of CWOQ-9 were 96.2 and 45.8%, respectively.Conclusions: WO occurred frequently at the early and middle stage of PD. CWOQ-9 was qualified as a pre-visiting screening tool for clinicians to better identify WO.

Plasma Short‐Chain Fatty Acids in Patients With Parkinson's Disease

Short-chain fatty acids are exclusively produced by gut microbiota and are reduced in feces of patients with Parkinson's disease (PD). The objective of this study was to conduct a case-control study on peripheral concentration of short-chain fatty acids based on evidence of pathologic changes in the blood-brain barrier in PD and the possible role of short-chain fatty acids in blood-brain barrier permeability. The plasma short-chain fatty acid concentration was measured in 38 PD and 33 normal controls using gas chromatography. The clinical characteristics of patients with PD and controls were evaluated, and dietary information was obtained using a food frequency questionnaire. Short-chain fatty acid concentrations were further compared after adjusting for age, sex, and significant food frequency questionnaire items. The concentrations of acetate, propionate, and butyrate did not differ between patients with PD and controls in unadjusted comparison. Dietary intakes of fibers, carbohydrates, lipids (total and fatty acids), and proteins did not differ between groups. After correction of covariates, acetic acid concentration was higher in patients with PD than in controls (116.47 ± 16.83 vs 108.20 ± 18.37 μmol/L; P = 0.010). In correlation analyses, acetic acid concentration was positively correlated (R = 0.374, P = 0.021) with age, propionic acid concentration was negatively correlated with UPDRS part III score (R = -0.376, P = 0.020) and use of entacapone (R = -0.325, P = 0.047), and butyric acid concentration was correlated with monoamine oxidase inhibitor use (R = 0.382, P = 0.018) and anticholinergic use (R = -0.385, P = 0.024). Plasma short-chain fatty acids were paradoxically increased in PD and were associated with disease severity and antiparkinsonian medications. Further studies are warranted to elucidate the relationships of gut dysbiosis and inflammation with plasma short-chain fatty acids. © 2020 International Parkinson and Movement Disorder Society.

Aromatic L‐Amino Acid Decarboxylase Gene Therapy Enhances Levodopa Response in Parkinson's Disease

BackgroundAs Parkinson's disease progresses, levodopa treatment loses efficacy, partly through the loss of the endogenous dopamine‐synthesizing enzyme L‐amino acid decarboxylase (AADC). In the phase I PD‐1101 study, putaminal administration of VY‐AADC01, an investigational adeno‐associated virus serotype‐2 vector for delivery of the AADC gene in patients with advanced Parkinson's disease, was well tolerated, improved motor function, and reduced antiparkinsonian medication requirements.ObjectivesThis substudy aimed to determine whether the timing and magnitude of motor response to intravenous levodopa changed in PD‐1101 patients after VY‐AADC01 administration.MethodsParticipants received 2‐hour threshold (0.6 mg/kg/h) and suprathreshold (1.2 mg/kg/h) levodopa infusions on each of 2 days, both before and approximately 6 months after VY‐AADC01. Infusion order was randomized and double blinded. Unified Parkinson's Disease Rating Scale motor scores, finger‐tapping speeds, and dyskinesia rating scores were assessed every 30 minutes for 1 hour before and ≥3 hours after start of levodopa infusion.ResultsOf 15 PD‐1101 patients, 13 participated in the substudy. Unified Parkinson's Disease Rating Scale motor score area under the curve responses to threshold and suprathreshold levodopa infusions increased by 168% and 67%, respectively, after VY‐AADC01; finger‐tapping speeds improved by 162% and 113%, and dyskinesia scores increased by 208% and 72%, respectively, after VY‐AADC01. Adverse events (mild/moderate severity) were reported in 5 participants during levodopa infusions pre–VY‐AADC01 and 2 participants post–VY‐AADC01 administration.ConclusionsVY‐AADC01 improved motor responses to intravenous levodopa given under controlled conditions. These data and findings from the parent study support further clinical development of AADC gene therapy for people with Parkinson's disease. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

An Unusual Case of Fever and Altered Mental Status

Parkinsonism hyperpyrexia syndrome (PHS) is a dysautonomic disorder that was described in 1981 for the first time. It can present after reduction or discontinuation of antiparkinson medications, co-prescription of neuroleptic medications, dehydration, hot weather, discontinuation of deep brain stimulator, and wearing off phenomenon.

A comparison of indirect and direct targeted STN DBS in the treatment of Parkinson\u2019s disease\u2014surgical method and clinical outcome over 15-year timespan

BackgroundDeep brain stimulation (DBS) in the subthalamic nucleus (STN) is used in advanced Parkinson’s disease (PD) for reducing motor fluctuations and the side effects of antiparkinsonian medication (APM). The development of neuroimaging has enabled the direct targeting of the STN. The aim of this study is to evaluate the outcome in patients with PD using STN DBS when changing from atlas-based indirect targeting method (iTM) to direct MRI-based targeting (dTM) assuming dTM is superior.MethodsTwenty-five consecutive PD patients underwent dTM STN DBS surgery from 2014 to 2017 with follow-up for 1 year. The neuroimaging, surgical method, outcome in Unified Parkinson’s Disease Rating Scale (UPDRS) scores, and reduction of APM are described and compared with the results of an earlier iTM STN DBS study.ResultsTwelve months after a dTM STN DBS, significant improvement (p < 0.001) was seen in six out of seven parameters of UPDRS when patients had medication (medON) and stimulation (stimON). The activities of daily living (UPDRSII) and motor scores (UPDRSIII) improved by 41% and 62%, respectively. Dyskinesias and fluctuations were both reduced by 81%. In dTM STN DBS group, the levodopa equivalent dose (LED) and the total daily levodopa equivalent dose (LEDD) were significantly decreased by 62% and 55%, respectively, compared with the baseline (p < 0.001). Five patients (20%) were without levodopa medication 12 months after the operation.ConclusionsThe development of surgical technique based on advanced neuroimaging has improved the outcome of PD STN DBS.

Are Anticholinergic Medications Associated With Increased Risk of Dementia and Behavioral and Psychological Symptoms of Dementia? A Nationwide 15-Year Follow-Up Cohort Study in Taiwan.

Background/ObjectiveIn previous reports, the usage of anticholinergic medications has been associated with an increased risk of dementia with prolonged usage or with a high Anticholinergic Cognitive Burden (ACB). This study aimed to investigate the association between anticholinergic medications and the risk of dementia using data from Taiwan's National Health Research Database (NHIRD).MethodsA total of 790,240 patients, with 197,560 patients receiving anticholinergic medications and 592,680 control patients (1:3) matched for sex, age, and index-year, were enrolled from the two million Longitudinal Health Insurance Dataset, a subdataset of the NHIRD, between 2000 and 2015. The time-dependent Cox regression analysis was used to explore the hazard ratio (HR) with a 95% confidence interval for the association between anticholinergics and the risk of dementia during the 15-year follow-up. The behavioral and psychological symptoms of dementia (BPSD) were recognized by the usage of psychotropics. The ACB ranged from zero to three, divided as score <1, 1–1.9, 2–2.9, 3–4.9,and ≧5. The sensitivity analysis was done by excluding the diagnoses of dementia in the first 2 or 4 years after anticholinergic usage.ResultsIn the anticholinergic usage cohort, the HR was 1.043 (95% CI = 0.958-1.212, p = 0.139) without a significant difference. The sensitivity analysis revealed no association between the usage of anticholinergics and the risk of dementia. Anticholinergic usage was not associated with BPSD. Male sex, patients of ages of 60–64 and ≧80, usage of antiparkinsonian medications, a history of Parkinson's disease, epilepsy, urinary incontinence, depression, bipolar disorder, and psychotic disorder were independent risk factors of dementia. Increased HRs for dementia were associated with an ACB ≥ 5 and an anticholinergic usage period ≥ 1,460 days.ConclusionIn this study, the usage of anticholinergics was not associated with the risk of dementia or BPSD in a 15-year follow-up study. However, patients with the male sex, patients with ages of 65–79 and ≧80, patients with some comorbidities, high ACB scores, and long anticholinergic treatment duration were associated with the risk of dementia.

The discovery and development of rasagiline as a new anti-Parkinson medication.

The discovery and development of rasagiline as a new anti-Parkinson medication.

Which Scale Best Detects Treatment Response of Tremor in Parkinsonism?

Several scales are available for rating the severity of tremor at present. However, the sensitivity to change of these instruments has remained to be clarified. To compare the sensitivity of the Fahn-Tolosa-Marin Tremor Rating Scale, the Part III of the Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and the MDS-UPDRS Tremor Scale to the effects of various antitremor treatments. Enrolling subjects with parkinsonism associated with tremor, we analyzed two scenarios: (1) tremor changes associated with acute levodopa challenge (n = 287) and (2) a 12-month outcome of different treatment options (n = 512) including deep brain stimulation (n = 146), levodopa/carbidopa intestinal gel infusion (n = 30), and initiating (n = 63) or adjusting oral antiparkinsonian medication (n = 273). Changes in tremor scales were assessed by effect size values (Cohen's d and eta-square). Part B of the Fahn-Tolosa-Marin Tremor Rating Scale was the most sensitive to acute levodopa challenge (Cohen's d = -1.04, η2 = 0.12). However, Part A of the Fahn-Tolosa-Marin Tremor Rating Scale showed the highest effect size, which was a small one (Cohen's d = -0.33, η2 = 0.03), for detecting a treatment-related change in the severity of tremor during long-term follow-up. The Fahn-Tolosa-Marin Tremor Rating Scale has a better ability to capture changes due to levodopa challenge or antiparkinsonian treatment than MDS-UPDRS Part III or MDS-UPDRS Tremor Scale.

Postural Behavior in Medicated Parkinson Disease Patients: A Preliminary Study Searching for Indicators to Track Progress.

Purpose:The establishment of early diagnostic methods for Parkinson disease (PD) is one of the key features to clinically control the rate of PD progression. This study aimed to give a first step toward recognizing the efficacy of multiple postural indices of balance control in differentiating medicated PD patients from health participants.Methods:Nine individuals with PD (Hoehn and Yahr Stage up to 2), 9 staged 2.5 and up, and 9 healthy age-matched Controls performed bipedal stances for 120 seconds with eyes either open or closed on a stable force platform. All participants with PD were under anti-Parkinsonian medication. Non-parametric tests investigated the effects of PD and visual input on postural indices extracted from the center of pressure coordinates.Results:Independent of the stage of the disease, individuals with PD presented faster and shakier body sway compared with Controls. Advanced stages of PD also revealed increased body sway length and variability. In addition, medio-lateral postural instability was more pronounced in all stages of PD when visual inputs were not allowed.Conclusion and Significance:Body sway velocity, jerkiness, length, and its variability revealed to be potential markers for subclinical signs of adjustments in the neuromechanisms of balance control and postural instability even at early stages of disease and under anti-Parkinsonian medication. Results produced here will direct future studies aiming to investigate the efficacy of these same indices on recognizing subclinical development of PD as well as those individuals susceptible to faster rates of progression.

For which patient subgroups are there positive outcomes from a medication review? A systematic review.

Background:A medication review is a possibility to assess and optimise a patient’s medicine. A model that includes a medication review and a follow-up seem to provide the best results. However, it is not known whether specific subgroups of patients benefit more from a medication review than others.Objective:This literature review summarises the evidence that is available on which patient subgroups exist positive outcomes from a medication review carried out in a primary care setting.Methods:We performed a PICO analysis to identify keywords for setting, medication review and effect. We then conducted a search using the PubMed database (2004 to 2019) to identify studies relevant for our investigation. A screening process was carried out based on either title or abstract, and any study that matched the aim and inclusion criteria was included. All matching studies were obtained and read, and were included if they met predefined criteria such as study design, medication review and primary care. The studies were divided into subgroups. First, each subgroup was divided according to the studies’ own definition. Secondly, each subgroup was allocated as either risk patients if the subgroup described a specific patient subgroup or risk medication, if the subgroup was defined as using a specific type of medication. This was done after discussion in the author group.Results:28 studies from a total of 935 studies were included. Identified studies were divided into either risk patients; frail, recently discharged or multimorbid patients, or risk medication; heart medication, antithrombotic medication, blood pressure lowering medication, antidiabetic medication, anti-Parkinson medication or medication increasing the risk of falls. The subgroups identified from a medication review in primary care were defined as being frail, recently discharged from hospital or multimorbid (risk patients), or defined as patients using anticoagulant or blood pressure lowering medication (risk medication). Most of the medication reviews in the studies that showed an economic effect included at least one follow-up and were delivered by a pharmacist.Conclusions:The literature review demonstrates that medication reviews delivered by pharmacists to specific subgroups of patients are a way of optimising the economic effect of medication reviews in primary care. This is obtained by reducing health-related costs or the number of contacts with primary or secondary health care services.

Insomnia and Excessive Daytime Sleepiness in Parkinson’s Disease Patient—A Review Article

Sleep-wake disorders play an important role among non-motor symptoms in Parkinson’s Disease, being a constant subject of research in recent years. There are a multitude of sleep-wake disturbances that worsen the patient’s quality of life, insomnia and excessive daytime sleepiness being two of the most frequent complaints. The aim of this review is to highlight the most relevant clinical trials conducted during the last 5 years, focusing on the problematic of insomnia and daytime sleepiness correlated with Parkinson’s Disease and its treatment. Three electronic databases (Pubmed, Science Direct and Google Scholar) were searched during March and April 2020 for articles on this topic, finally selecting 21 most relevant articles that we have included in this review. Interesting aspects regarding correlation between sleep-wake disorders and Parkinson’s disease were found, showing that non-motor symptoms may be independent of the disease itself. We discussed the most recent advances in treatment opportunities and the adverse effects, with insomnia and daytime sleepiness among the most common complaints. Besides newly developed pharmacological therapy, consisting in mostly dopaminergic agonists or levodopa adjuvant drugs. Other possibly effective therapies on sleep-wake disorders such as deep brain stimulation, dietary changes, bright light therapy and alternative medicine protocols are also reviewed. Insomnia and excessive daytime sleepiness are common complaints in Parkinson’s disease patients, being either self-standing non-motor symptoms or adverse effects of the antiparkinsonian medication, diminishing patient’s quality of life. The effervescence of research on this topic shows promising results, with new clinical trials still to come in the near future.

Comparative Study on the Use of Long-Acting Injectable Antipsychotics in Three Different Psychiatric Treatment Facilities in Saskatchewan, Canada

This study examined the prevalence of Long Acting Injectable (LAI) antipsychotics prescription and explored the nature and scope of such prescriptions in the context of polypharmacy in three major psychiatric treatment facilities in Saskatchewan, Canada. A cross-sectional study approach was used to collect data on LAI antipsychotics prescription details and de-identified demographics on all patients on admission on a specified date at the three study sites. Despite the availability of second generation LAI antipsychotics, first generation LAI antipsychotics accounted for 83.3% of the prescriptions (N = 96). Risperdal Consta was the only second generation LAI antipsychotic medication prescribed out of the six LAI antipsychotics in use. The most commonly prescribed LAI antipsychotic was zuclopenthixol decanoate (44.1%, N = 53). Most of the LAI antipsychotics were prescribed within the recommended dosages. Biweekly administration was the most common interval for the prescription of LAI antipsychotics (75%, N = 90). Polypharmacy was present amongst all patients including those on LAI antipsychotics. Co-prescription of antiparkinsonian medication was associated with the prescription of LAI antipsychotics. Patients with the diagnosis of Schizophrenia had more prescriptions for Zuclopenthixol decanoate (44.4%) and Risperidone Consta (24.4%) than those with the diagnoses of bipolar disorder (23.3% and 14.7%, respectively). A longitudinal approach to examining the LAI antipsychotic prescription practice would help to determine if concomitant prescription of LAI antipsychotics is associated with decrease in oral antipsychotic load.

Low Sustainment of High-Dose Oral Medication Regimens for Advanced Parkinson's Disease in Medicare Beneficiaries.

Increasing doses of oral antiparkinson medications are indicated in advanced Parkinson's disease (PD), but little is known about sustainment of high-dose regimens. To investigate sustainment of high-dose oral medication regimens in Medicare beneficiaries with incident advanced PD. This retrospective cohort study utilized 100%fee-for-service Medicare claims from 2011-2013. We identified advanced PD using a pharmacy claims-based proxy and selected patients who initiated a new high-dose oral medication regimen (daily levodopa equivalent dose [LED] >1000 mg/day for ≥30 days) in 2012. In the following 12 months, we examined: 1) annual proportion of days covered (PDC)≥0.80 and 2) presence of a ≥ 90 day continuous gap at varying dosage thresholds: the initial >1000 mg/day, >800 mg/day, >500 mg/day, or >0 mg/day. We identified 9,405 patients with advanced PD (mean age 77.4 [SD 6.8] years; 53%men). Only 5%maintained a regimen of >1000 mg/day at PDC ≥0.80; 75% had a ≥ 90-day gap in that dosage level. At a dosage threshold of >800 mg/day, 20% had a PDC ≥0.80 and 53% had a ≥ 90-day gap; at >500 mg/day, 56% had a PDC ≥0.80 and 19%had a ≥ 90-day gap; and at >0 mg/day (any dose), 76% had a PDC ≥0.80 and only 10%had a≥90-day gap. Few patients with advanced PD sustained a high-dose oral medication regimen in the year following initiation, but most sustained a substantially lower-dose regimen. Strategies to improve advanced PD treatment are needed.