Antiparkinsonian Drugs Research Articles

Binding of the Dual-Action Anti-Parkinsonian Drug AG-0029 to Dopamine D2 and Histamine H3 Receptors: A PET Study in Healthy Rats.

Introduction: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor dysfunction and a diverse range of nonmotor symptoms. Functional relationships between the dopaminergic and histaminergic systems suggest that dual-action pharmaceuticals like AG-0029 (D2/D3 agonist/H3 antagonist) could ameliorate both the motor and cognitive symptoms of PD. The current study aimed to demonstrate the interaction of AG-0029 with its intended targets in the mammalian brain using positron emission tomography (PET). Methods: Healthy male Wistar rats were scanned with a small-animal PET camera, using either the dopamine D2/D3 receptor ligand [11C]raclopride or the histamine H3 receptor ligand [11C]GSK-189254, before and after treatment with an intravenous, acute, single dose of AG-0029. Dynamic [11C]raclopride PET data (60 min duration) were analyzed using the simplified reference tissue model 2 (SRTM2) with cerebellum as reference tissue and the nondisplaceable binding potential as the outcome parameter. Data from dynamic [11C]GSK-189254 scans (60 min duration) with arterial blood sampling were analyzed using Logan graphical analysis with the volume of distribution (VT) as the outcome parameter. Receptor occupancy was estimated using a Lassen plot. Results: Dopamine D2/3 receptor occupancies in the striatum were 22.6 ± 18.0 and 84.0 ± 3.5% (mean ± SD) after administration of 0.1 and 1 mg/kg AG-0029, respectively. In several brain regions, the VT values of [11C]GSK-189254 were significantly reduced after pretreatment of rats with 1 or 10 mg/kg AG-0029. The H3 receptor occupancies were 11.9 ± 8.5 and 40.3 ± 11.3% for the 1 and 10 mg/kg doses of AG-0029, respectively. Conclusions: Target engagement of AG-0029 as an agonist at dopamine D2/D3 receptors and an antagonist at histamine H3 receptors could be demonstrated in the rat brain with [11C]raclopride and [11C]GSK-189254 PET, respectively. The measured occupancy values reflect the previously reported high (subnanomolar) affinity of AG-0029 to D2/D3 and moderate (submicromolar) affinity to H3 receptors.

Entacapone microsponges in the treatment of acute Parkinson’s disease

Objective: The current study was based on the many different dose frequencies of entacapone, an anti-Parkinson's drug that was loaded with microsponges to change the dose frequency of the drug administration. Methods: Microsponges were made utilizing polymethacrylate polymers such as eudragit L100, eudragit S 100, and eudragit RS 100 in various ratios using a quasi-emulsion solvent diffusion, ratios such as (1:0.5, 1:1, 1:1.5 and 1:2). These polymers release the drug in a controlled manner. The polymer used for the preparation of microsponges was useful in forming sponges in which the drug was entrapped. By using the 3 polymers,12 formulations were prepared. Results: FT-IR and DSC tests were carried out and it was clear from the FT-IR and DSC spectra that there were no interactions between the entacapone and the polymer. out of 12 formulations 3 formulations were selected as optimized formulations based on the production yield (%), encapsulating efficiency, drug loading (%), and SEM analysis says that the produced microsponges formulation was extremely porous, indicating their potential for increased drug loading.

Prescription Pattern of Monoamine Oxidase B Inhibitors Combined with Levodopa: A Retrospective Observational Analysis of Italian Healthcare Administrative Databases.

BackgroundParkinson’s disease is still incurable, and several factors are considered when defining pharmacological therapy.ObjectiveThe aim of this study was to describe the prescription pattern of monoamine oxidase B inhibitors (MAO-BIs) marketed in Italy (selegiline, rasagiline, safinamide) as an add-on to levodopa among new users of MAO-BIs, from the perspective of the Italian National Health Service.Patients and MethodsThrough cross-linkage of administrative healthcare data in the Ricerca e Salute (ReS) database, adults with a supply of one or more MAO-BIs in 2017, and with no other MAO-BI use since 2013, were selected. Levodopa had to be supplied within 30 days before/after the MAO-BI. The incidence, use, sex, age, comorbidities, 2-year prescription patterns (i.e., switches, proportion of treated patients per semester/year, mean daily milligrams/monthly tablets supplied, discontinuation, change to other anti-Parkinson drug) of patients taking MAO-BIs were provided.ResultsIn 2017, 1059 new users received an MAO-BI (incidence 22.6 × 100,000 adults) combined with levodopa: 502 subjects (10.7 × 100,000) were treated with selegiline, 161 (3.4 × 100,000) were treated with rasagiline, and 396 (8.4 × 100,000) were treated with safinamide. The cohorts mainly consisted of males with a median age of ≥ 74 years. Treatment incidences increased with age. Switches occurred in 18.0%, 11.0%, and 4.3% of the selegiline, rasagiline, and safinamide cohorts, respectively. Most of the patients switching from selegiline/safinamide changed to rasagiline, while most of the patients switching from rasagiline changed to safinamide. From the first to second years, patient numbers reduced by ≤ 50%, and the daily milligrams/monthly tablets slightly increased. Six-month discontinuation occurred in > 50% of all cohorts, and ≥ 65% of discontinuing patients changed to another anti-Parkinson drug.ConclusionsThis analysis described the heterogeneous use of MAO-BIs as an add-on to levodopa in Italy. Further clinical trials and real-world studies are encouraged to update the few existing guidelines and to align clinical practice strategies.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40801-022-00308-4.

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BiopolymersVolume 113, Issue 6 e23446 COVER IMAGEFree Access Cover Image First published: 23 June 2022 https://doi.org/10.1002/bip.23446AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Graphical Abstract Ropinirole hydrochloride (RH) is a promising anti-Parkinson's disease drug but suffers from low-clinical potency, often attributed to poor oral bioavailability, short plasma half-life and metabolism by the liver. Darwish et al. report the preparation of two nanoformulations to enhance delivery of RH to the brain: a self-assembled core-shell nanocapsule of RH and methoxy poly(ethylene glycol)-b-poly(caprolactone) coated with chitosan, and a RH-loaded chitosan-alginate polyelectrolyte nanocomplex. The mucoadhesive properties endowed by the chitosan and alginate promote RH delivery across the nasal mucosa and higher brain uptake of RH is seen in albino mice when the formulations are administered intranasally compared with intravenously. DOI: 10.1002/bip.23489 Volume113, Issue6June 2022e23446 RelatedInformation

Use of levodopa-carbidopa intestinal gel to treat patients with multiple system atrophy

BackgroundLevodopa-carbidopa intestinal gel (LCIG) is an effective treatment for late-stage Parkinson's disease (PD) but had not been evaluated in levodopa-responsive patients with the parkinsonian variant of multiple system atrophy (MSA-P) and motor fluctuations. We aimed to assess the safety of LCIG in MSA-P patients. MethodsIn a retrospective, single-center study, we analyzed clinical and treatment-related data for all patients with MSA-P or PD treated with LCIG between December 2004 and November 2017. Adverse events (AEs) were classified into three classes: AEs related to gastrointestinal effects or to the PEG-J procedure, AEs related to the device, and AEs related to the pharmacological effect of LCIG. Results7 MSA-P and 63 PD patients had been treated with LCIG for a median [interquartile range] period of 31 [16;43] and 19 [8;45] months, respectively. There were no significant intergroup differences in safety. Enteral nutrition was introduced at the same time as LCIG treatment in 4 (57%) MSA-P patients. In the MSA-P and PD groups, LCIG was associated with a better Global Clinical Impression score and discontinuation of oral anti-parkinsonian drugs (in 43% and 27% of cases, respectively). ConclusionsLCIG treatment is feasible in MSA-P patients with severe motor complications. The safety profile is similar to that seen in PD.

Formulation and Evaluation of Transdermal Patches of Selegiline

Selegiline is an antiparkinsonian drug. It is a MAO-B enzyme inhibitor. It undergoes hepatic first pass metabolism and it result in 10% bioavailability on oral administration. So it was designed to formulate transdermal patches of Selegiline HCl for enhancing the bioavailability and patient compliance. Different formulation were prepared by different grades and varying concentration of polymer by solvent casting method. PG was used as permeation enhancer. The films were subjected to evaluation parameters like weight variation, thickness, moisture content, tensile strength, folding endurance, drug content and in-vitro drug release.

Dynamics of Nigral Iron Accumulation in Parkinson's Disease: From Diagnosis to Late Stage.

Higher nigral iron has been reported in Parkinson's disease (PD). The aim is to understand the dynamics of nigral iron accumulation in PD and its association with drug treatment. Susceptibility magnetic resonance imaging data were obtained from 79 controls and 18 drug-naive (PDDN ) and 87 drug-treated (PDDT ) PD patients. Regional brain iron in basal ganglia and cerebellar structures was estimated using quantitative susceptibility mapping. Nigral iron was compared between PDDN and PDDT subgroups defined by disease duration (early [PDE, <2 years], middle [PDM, 2-6 years], and later [PDL, >6 years]). Associations with both disease duration and types of antiparkinson drugs were explored using regression analysis. Compared to controls, PDDN had lower iron in the substantia nigra (P=0.018), caudate nucleus (P=0.038), and globus pallidus (P=0.01) but not in the putamen or red nucleus. In contrast, PDDT had higher iron in the nigra (P < 0.001) but not in other regions, compared to either controls or PDDN . Iron in the nigra increased with disease duration (PDE > PDDN [P=0.001], PDM > PDE [P=0.045]) except for PDM versus PDL (P=0.226). Levodopa usage was associated with higher (P=0.013) nigral iron, whereas lower nigral iron was correlated with selegiline usage (P=0.030). Nigral iron is lower before the start of dopaminergic medication and then increases throughout the disease until it plateaus at late stages, suggesting increased iron may not be an etiological factor. Interestingly, PD medications may have differential associations with iron accumulation that need further investigation. © 2022 International Parkinson and Movement Disorder Society.

High rates of blood transfusion associated with Parkinson’s disease

BackgroundAs evidence continues to accumulate regarding the multi-organ dysfunction associated with Parkinson’s disease (PD), it is still unclear as to whether PD increases the risk of hematological pathology. In this study, the authors investigate the association between PD and hematological pathology risk factors.MethodsThis retrospective cohort analysis was conducted using 8 years of the National Readmission Database. All individuals diagnosed with PD were queried at the time of primary admission. Readmissions, complications, and risk factors were analyzed at 30-, 90-, 180-, and 300-day intervals. Statistical analysis included multivariate Gaussian-fitted modeling using age, sex, comorbidities, and discharge weights as covariates. Coefficients of model variables were exponentiated and interpreted as odds ratios.ResultsThe database query yielded 1,765,800 PD patients (mean age: 76.3 ± 10.4; 44.1% female). Rates of percutaneous blood transfusion in readmitted patients at 30, 90, 180, and 300 days were found to be 8.7%, 8.6%, 8.3%, and 8.3% respectively. Those with anti-parkinsonism medication side effects at the primary admission had increased rates of gastrointestinal (GI) hemorrhage (OR: 1.02; 95%CI: 1.01–1.03, p < 0.0001) and blood transfusion (OR: 1.06; 95%CI: 1.05–1.08, p < 0.0001) at all timepoints after readmission. PD patients who experienced GI hemorrhage of any etiology, including as a side effect of anti-parkinsonism medication, were found to have significantly higher rates of blood transfusion at all timepoints (OR: 1.14; 95%CI: 1.13–1.16, p < 0.0001).ConclusionsBlood transfusions were found to be significantly associated with anti-parkinsonism drug side effects and GI hemorrhage of any etiology.

Treatment and Care for Elderly Patients with Dementia with Lewy Bodies Presenting with Delusional Misidentification Syndrome Including Capgras Syndrome: Severe Psychiatric Symptoms Associated with Dementia with Lewy Bodies

The treatment and care for severe psychiatric symptoms associated with dementia with Lewy bodies is challenging. This is especially true for elderly patients because the use of antipsychotics is associated with an attendant mortality risk. In this article, dementia patients with Lewy bodies who presented with severe psychiatric symptoms such as Capgras syndrome (delusional misidentification syndrome), are described, and pharmacological and non-pharmacological strategies to address these symptoms are discussed. Measures to be avoided include antipsychotic administration and physical restraint, both of which often lead to medical conditions and a bedridden status. Conversely, changing antiparkinsonian drugs (levodopa rather than dopamine agonists), cholinesterase inhibitor administration, physical rehabilitation, and providing a supportive, patient-friendly environment may help improve psychiatric symptoms or maintain functionality. In some cases, electroconvulsive therapy may be effective for severe psychiatric symptoms.

Time to onset of drug-induced parkinsonism: Analysis using a large Japanese adverse event self-reporting database.

Whether there are differences in the time to onset of drug-induced parkinsonism (DIP) depending on the type of drugs causing DIP remains uncertain, so that question was investigated here using a large real-world database. Fourteen DIP-related drug categories were defined to perform a disproportionality analysis using a large Japanese pharmacovigilance database containing more than 600,000 self-reported adverse events (AEs) recorded between April 2004 and September 2021 to identify AEs indicating "parkinsonism" in association with the defined drug categories. The time from drug administration to the onset of DIP was comparatively analyzed. Results indicated that the median time to onset was shorter than 1 month in more than half of the cases of DIP; it was shortest with peripheral dopamine antagonists (median: 0.1 weeks), followed by benzodiazepine (median: 0.5 weeks), butyrophenone (median: 0.7 weeks), novel antidepressants (median: 2.5 weeks), atypical antipsychotics (median: 3.3 weeks), other antidepressants (e.g., lithium, median: 3.7 weeks), and benzamide (median: 4.5 weeks). In contrast, anti-dementia drugs, tricyclic antidepressants, and antiepileptic drugs resulted in a relatively longer time to onset (median: 9.9, 17.2, and 28.4 weeks, respectively). In addition, a maximum delay of even longer than 2 years was reported for benzamide (846 weeks), anti-Parkinsonism drugs (382 weeks), phenothiazine (232 weeks), atypical antipsychotics (167 weeks), anti-dementia drugs (161 weeks), and benzodiazepines (120 weeks). The current results suggested that the characteristics of the time to onset of DIP may substantially differ depending on the type of drug causing that DIP. This finding may help when diagnosing patients with parkinsonism.

Non-Invasive Neuromodulation in the Rehabilitation of Pisa Syndrome in Parkinson's Disease: A Randomized Controlled Trial

BackgroundPisa syndrome (PS) is a frequent postural complication of Parkinson's disease (PD). PS poorly responds to anti-parkinsonian drugs and the improvement achieved with neurorehabilitation tends to fade in 6 months or less. Transcranial direct current stimulation (t-DCS) is a non-invasive neuromodulation technique that showed promising results in improving specific symptoms in different movement disorders.ObjectivesThis study aimed to evaluate the role of bi-hemispheric t-DCS as an add-on to a standardized hospital rehabilitation program in the management of PS in PD.MethodsThis study included 28 patients with PD and PS (21 men, aged 72.9 ± 5.1 years) who underwent a 4-week intensive neurorehabilitation treatment and were randomized to receive: i) t-DCS (t-DCS group, n = 13) for 5 daily sessions (20 min−2 mA) with bi-hemispheric stimulation over the primary motor cortex (M1), or ii) sham stimulation (sham group, n = 15) with the same duration and cadence. At baseline (T0), end of rehabilitation (T1), and 6 months later (T2) patients were evaluated with both trunk kinematic analysis and clinical scales, including UPDRS-III, Functional Independence Measure (FIM), and Numerical Rating Scale for lumbar pain.ResultsWhen compared to the sham group, the t-DCS group achieved a more pronounced improvement in several variables: overall posture (p = 0.014), lateral trunk inclination (p = 0.013) during upright standing position, total range of motion of the trunk (p = 0.012), FIM score (p = 0.048), and lumbar pain intensity (p = 0.017).ConclusionsOur data support the use of neuromodulation with t-DCS as an add-on to neurorehabilitation for the treatment of patients affected by PS in PD.

Biocompatible mucoadhesive nanoparticles for brain targeting of ropinirole hydrochloride: Formulations, radiolabeling and biodistribution.

Two nanoformulations with mucoadhesive properties and brain-targeting mechanisms were designed to deliver the anti-Parkinson's drug, ropinirole hydrochloride (RH). In the first formulation, RH and the amphiphilic block copolymer methoxy poly(ethylene glycol)-b-poly(caprolactone) were assembled in a core-shell morphology followed by coating with a mucoadhesive chitosan outer layer producing a multilayer vehicle (MLV). In the second formulation, RH was encapsulated during the polyelectrolyte complexation of two natural polymers, chitosan and alginate producing RH-loaded chitosan-alginate polyelectrolyte (PEC) nanocomplex. Conditions of each formulation were adopted for optimal drug loading. Physico-chemical characterization of the prepared formulations (particle size, polydispersity index and zeta-potential) exhibited stable monodispersed nanoparticles. RH was radiolabeled by I-131 radiotracer in a high-radiochemical yield. Biodistribution and brain targeting of RH from the prepared formulations were studied after administration of 131 I-RH-loaded nanoparticles to albino mice via intranasal and intravenous routs. Elevated brain radioactivity was detected post IN administration of (131 I-RH/PCL-PEG/CS) nanoparticles and (131 I-RH/CS-ALG) nanoparticles comparing with the IN administrated RH solutions (Cmax =2.8 ± 0.3, 2 ± 0.3, 0.93 ± 0.03% radioactivity/g, 1h post administration, respectively). This demonstrated that a relatively high-brain targeting could be achieved via intranasal route of administration of RH-loaded nanoparticles. The proposed models are further potential for application to deliver many other brain-targeting therapeutics.

The risk of melanoma with rasagiline compared with other antiparkinsonian medications: A retrospective cohort study in the United States medicare database.

PurposeCompare the risk of melanoma between initiators of rasagiline or other antiparkinsonian drugs (APDs) in a Parkinson's disease (PD) population.MethodsA retrospective cohort study was conducted in the US Medicare claims research database (2006–2015) in adults aged ≥65 years with PD claims. Other APD initiators were randomly matched (4:1) to rasagiline initiators on age, sex, and cohort entry year. Cutaneous melanoma events were identified by a validated claims algorithm. Incidence rates (IRs), incidence rate ratios (IRRs), and Cox‐adjusted hazard ratios (HRs) for melanoma comparing rasagiline with other APD initiators were calculated and analyzed by duration of study medication use and cumulative dose of rasagiline. Potential indicators of surveillance bias were explored.ResultsAmong 23 708 rasagiline initiators and 96 552 matched APD initiators, the crude IR of melanoma/100 000 person‐years was 334.3 (95% confidence interval [CI], 291.5–381.6) and 208.2 (95% CI, 190.1–227.5), respectively (crude IRR 1.61; 95% CI, 1.36–1.89). The adjusted HR was 1.37 (95% CI, 1.14–1.65) and increased with longer rasagiline exposure and higher cumulative rasagiline doses. Rasagiline initiators more frequently had dermatologist visits or skin biopsies before cohort entry than APD initiators and had a higher incidence of nonmelanoma skin cancer during follow‐up (crude IRR, 1.44; 95% CI, 1.35–1.54).ConclusionsA small increased incidence of melanoma with exposure to rasagiline compared with other APDs was observed. Although the pattern with dose and duration is consistent with a hypothesized biologic effect, the increased skin cancer surveillance among rasagiline users suggests surveillance bias as a contributing explanation for the observed results.

Development of the ADFICE_IT Models for Predicting Falls and Recurrent Falls in Community-Dwelling Older Adults: Pooled Analyses of European Cohorts With Special Attention to Medication.

BackgroundUse of fall prevention strategies requires detection of high-risk patients. Our goal was to develop prediction models for falls and recurrent falls in community-dwelling older adults and to improve upon previous models by using a large, pooled sample and by considering a wide range of candidate predictors, including medications.MethodsHarmonized data from 2 Dutch (LASA, B-PROOF) and 1 German cohort (ActiFE Ulm) of adults aged ≥65 years were used to fit 2 logistic regression models: one for predicting any fall and another for predicting recurrent falls over 1 year. Model generalizability was assessed using internal–external cross-validation.ResultsData of 5 722 participants were included in the analyses, of whom 1 868 (34.7%) endured at least 1 fall and 702 (13.8%) endured a recurrent fall. Positive predictors for any fall were: educational status, depression, verbal fluency, functional limitations, falls history, and use of antiepileptics and drugs for urinary frequency and incontinence; negative predictors were: body mass index (BMI), grip strength, systolic blood pressure, and smoking. Positive predictors for recurrent falls were: educational status, visual impairment, functional limitations, urinary incontinence, falls history, and use of anti-Parkinson drugs, antihistamines, and drugs for urinary frequency and incontinence; BMI was a negative predictor. The average C-statistic value was 0.65 for the model for any fall and 0.70 for the model for recurrent falls.ConclusionCompared with previous models, the model for recurrent falls performed favorably while the model for any fall performed similarly. Validation and optimization of the models in other populations are warranted.

Rasagiline, sleep quality and well-being in Parkinson's disease: a pilot study.

Sleep disordersand excessive daytime sleepiness are among the commonest nonmotor symptoms in Parkinson disease (PD) and can contribute to significantly lower quality of life in affected patients. Various antiparkinson drugs exert a relevant influence on sleep quality, daily vigilance and well-being. In the latest years, administration of monoamine oxidase type B inhibitor (iMAO-B) medications in PD, especially rasagiline, has gained importance due to the hypothesized neuroprotective effect of these agents. Whereas the ‘wakepromoting’ effect of selegine, due to its activating amphetamine-like compounds, has been already described, less is known regarding the effect of rasagiline, a world-wide used iMAO-B drug. A pilot study was carried out to analyze the effects of rasagiline on sleep and healthrelated quality of life in a small cohort of PD patients. According to our results, PD patients treated with rasagiline referred better sleep quality, required less frequently hypnotic medication, complained of lower daytime sleepiness and presented higher scores in social functioning, perceived energy levels and emotional well-being. Albeit limited by the small sample size, our study suggests an intriguing role of rasagiline in improving sleep and quality of life in PD patients. Further studies are necessary to confirm our preliminary observations.

Incidence of Parkinson's disease in French women from the E3N cohort study over 27years of follow-up.

Parkinson's disease (PD) is an uncommon disease with a long prodromal period and higher incidence in men than women. Large cohort studies of women with a long follow-up are needed. Within the E3N French cohort study (98,995 women, 40-65years at baseline), we identified 3,584 participants who self-reported PD or used anti-parkinsonian drugs over 27years (1992-2018). We obtained medical records to validate PD diagnosis (definite, probable, possible, no). When medical records were not available, we used a validated algorithm based on drug claims to predict PD status. We retained a PD diagnosis for 1,294 women (medical records, 62%; algorithm, 38%). After exclusion of prevalent/possible cases, cases without age at diagnosis, and women lost to follow-up, our analyses included 98,069 women, of whom 1,200 had incident PD (mean age at diagnosis = 71.8years; incidence rate = 0.494/1,000 person-years). Age-adjusted incidence rates increased over the six first years of follow-up, possibly due to healthy volunteer bias, and remained stable thereafter, similar to incidence rates in women from Western Europe. Forty three percent of PD cases occurred after 20years of follow-up (2012-2018). The cumulative incidence of PD from 50 to 90years was 2.41% (95% confidence interval [CI] = 2.27-2.65). PD incidence was lower in ever than never smokers (hazard ratio = 0.86, 95% CI = 0.76-0.96). In conclusion, we estimated PD incidence rates in French women over a 27-year follow-up, and showed stable incidence between 2002 and 2018. The long follow-up and large sample size make this study a valuable resource to improve our knowledge on PD etiology in women.

Dopamine receptor agonists: standard and non-standard applications in medicine

Dopamine receptor agonists (DRA) are a class of therapeutic drugs able to directly stimulate dopaminergic receptors facilitating a stronger effect of the endogenous dopamine, which is widely used in treatment of diseases that are accompanied with dopaminergic neurotransmission deficiency. A classical hypodopaminergic condition is Parkinson’s disease and DRA are traditionally associated with it. However, even the first DRA, Bromocriptine, widely adopted in PD treatment, was initially registered as a medication for treatment of prolactinaemia and associated pituitary adenomas and is still widely used in gynecology and endocrinology. In several countries DRA are used in treatment of diabetes, eating disorders, and addictions. Dopamine is the cardinal neurotransmitter of the emotional control and the main neurotransmitter of the reward system, and that defines the interest for researching the dopaminergic agents in treatment of primarily mental illnesses, as well as correction of secondary affective disorders. The experimental effectiveness of ADR in slowing down the rate of progression of the neurodegenerative process in severe incurable diseases, as well as potential neuroprotection in cerebrovascular insufficiency, will allow in the future to determine the criteria for the use of ADR in these non-standard situations, which may even lead to a change in clinical recommendations for the treatment of individual nosologies. Presented in this article are both traditional uses of DRA and an overview of non-standard applications of this class of medications with a discussion of recent studies. In the future, the likelihood of a rethinking of ADRs as a class of only antiparkinsonian drugs, with the expansion of their therapeutic indications.

Drug-induced Delusional Infestation.

It is considered that certain drugs might induce delusional infestation, yet, to date, no studies have been performed to identify the pharmacodynamics associated with these treatments. The aim of this review is to summarize current available knowledge of drug-induced delusional infestation. A literature search was performed for primary studies on suspected drugs reported to induce delusional infestation. Included articles were evaluated systematically using the Naranjo criteria. In addition, drug mechanisms of action were compared. The final selection included 31 studies, in which a total of 26 classes of drugs were identified. Anti-Parkinson drugs were most frequently associated with delusional infestation, followed by antidepressants, antiepileptics, antibiotics, prescription stimulants, and a few other drug groups. The current available literature suggests that the onset of delusional infestation is initiated by drug-induced alterations in neurotransmitter levels, predominantly dopamine, in the central nervous system.

Management of Medication-Induced Psychiatric Disorders.

Management of Medication-Induced Psychiatric Disorders.

Adherence to Medication among Parkinson's Disease Patients Using the Adherence to Refills and Medications Scale.

Objectives Adherence to medication is an important factor that can influence Parkinson's disease (PD) control. We aimed to explore patients' adherence to antiparkinsonian medication and determine factors that might affect adherence to medications among PD patients. Methods A cross-sectional, exploratory survey of PD patients treated with at least one antiparkinsonian drug and with a total score of MoCA (Montreal Cognitive Assessment) ≥26 was conducted. The final sample included 112 PD patients. A patient's adherence was assessed through ARMS (Adherence to Refills and Medications Scale). ARMS scores higher than 12 were assumed lower adherence. In addition, each patient underwent neurological examination, assessment of depression, anxiety, and evaluation of the presence of PD nonmotor symptoms. Results The mean ARDS value in our cohort was 14.9 ± 2.5. Most PD patients (74.1%) reported lower adherence to their medication. Participants in the lower adherence group were younger at PD onset, had significantly higher UPDRS (Unified PD Rating Scale) scores, as well as UPDRS III and UPDRS IV subscores, HARS (Hamilton Anxiety Rating Scale), and NMSQuest (Non-Motor Symptoms Questionnaire for PD) scores compared to the fully adherent group (p=0.013, p=0.017, p=0.041, p=0.043, and p=0.023, respectively). Among nonmotor PD symptoms, the presence of cardiovascular, apathy/attention-deficit/memory disorders, hallucinations/delusions, and problems regarding changes in weight, diplopia, or sweating were associated with lower adherence. Multivariate regression analysis revealed depression as the strongest independent predictor of lower adherence. Conclusion Depressed PD patients compared to PD patients without clinical depression had a three times higher risk for lower adherence to pharmacotherapy. Recognition and adequate treatment of depression might result in improved adherence.