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The Journal of Neuroscience Nursing :... Oct 2022INTRODUCTION: Parkinson disease (PD) affects approximately 1% of women and men worldwide, particularly older than 60 years. It is a multisystem and neurodegenerative... (Review)
Review
INTRODUCTION: Parkinson disease (PD) affects approximately 1% of women and men worldwide, particularly older than 60 years. It is a multisystem and neurodegenerative disease with genetics and environmental factors that result in deficits in the production of neurotransmitters, including dopamine. The levodopa-carbidopa intestinal gel (LCIG) system delivers a continuous infusion of levodopa directly into the proximal small intestine via percutaneous endoscopic jejunostomy, largely bypassing gastric emptying and absorption problems and producing more stable plasma concentrations of levodopa, eliminating the development of motor complications (dyskinesias). The aim of this review was to summarize scientific evidence on the nursing role that, together with the multidisciplinary team, made the patient's choice in this therapeutic path (pre-LCIG phase). METHODS: A literature review was carried out, conducted on the MEDLINE databases (through PubMed), The Cochrane Library, Google Scholar, and CINAHL (through EBSCO). Relevant articles for the topic were found to identify indexed primary studies that investigated the relationship between the nurse and the patient/caregiver with PD who undertakes treatment with LCIG according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. RESULTS: Nineteen studies were included in the review. The selected studies suggested how the pre-LCIG phase of patient choice and the subsequent education and training could avoid selection errors for these therapeutic paths. CONCLUSION: Trained and specialized nursing staff who carry out an adequate pre-LCIG phase associated to the multidisciplinary team improved the choice of the patient and the start of treatment and, consequently, the quality of life of PD patients.
Topics: Antiparkinson Agents; Carbidopa; Drug Combinations; Female; Gels; Humans; Levodopa; Male; Neurodegenerative Diseases; Parkinson Disease; Quality of Life
PubMed: 35852970
DOI: 10.1097/JNN.0000000000000671 -
Journal of Neural Transmission (Vienna,... Nov 2023The standard of care is a term that refers to the level of care, skill, and treatment that a healthcare provider should offer to a patient based on the current... (Review)
Review
The standard of care is a term that refers to the level of care, skill, and treatment that a healthcare provider should offer to a patient based on the current scientific evidence and the level of medical knowledge available in the field. For Parkinson's disease (PD), the standard care is mostly considered to be oral treatment with dopaminergic drugs, particularly levodopa which remains the 'gold standard'. However, effective management with levodopa during the later stages of the disease becomes increasingly challenging due to the ongoing neurodegenerative process, the consequences of its pulsatile dopaminergic stimulation, and the gastrointestinal barriers to effective drug absorption. As a result, the concept of applying continuous dopaminergic stimulation has emerged with infusion therapies (continuous subcutaneous apomorphine, levodopa-carbidopa intestinal gel, and levodopa-entacapone-carbidopa intestinal gel infusion). These therapies seek to provide continuous stimulation of striatal dopamine receptors that is efficient not only in alleviating clinical symptoms, but also in delaying, reducing, and possibly preventing the onset of levodopa-related motor (fluctuations, dyskinesia) and non-motor complications; and they are also associated with clinically relevant side effects. Clinical studies and real-life experience support the notion that infusion therapies should be accepted as part of the standard of care for patients with advanced PD who have refractory, severe, and disabling motor complications that affect their quality of life. However, they should be considered based on the needs of individualized patients and the access to these advanced therapies needs to be made more accessible to the general PD population.
Topics: Humans; Levodopa; Carbidopa; Parkinson Disease; Quality of Life; Standard of Care; Antiparkinson Agents
PubMed: 37930456
DOI: 10.1007/s00702-023-02708-4 -
Neurological Sciences : Official... Aug 2020Treatment of Parkinson's disease with levodopa/carbidopa/entacapone (LCE) has been studied for a long time. However, the efficacy and safety of LCE in the treatment of... (Meta-Analysis)
Meta-Analysis Review
Treatment of Parkinson's disease with levodopa/carbidopa/entacapone (LCE) has been studied for a long time. However, the efficacy and safety of LCE in the treatment of early Parkinson's disease (PD) still need to be assessed. Our objective was to do a meta-analysis of relevant randomized controlled trials (RCTs) to evaluate the efficacy and safety of LCE for early PD. PubMed, Embase, the Cochrane Library, and the Web of Science were searched for RCTs with "levodopa/carbidopa/entacapone" and "Parkinson's disease" as keywords. The search period was from inception to October 2018. The quality of included studies was strictly evaluated. We evaluated the quality of included studies strictly and six studies met all inclusion criteria. The results showed that LCE could improve activities of daily living and motor function in PD patients. However, LCE therapy was associated with higher risks of total AEs and single AEs compared with traditional therapy.
Topics: Antiparkinson Agents; Carbidopa; Catechols; Drug Combinations; Humans; Levodopa; Nitriles; Parkinson Disease
PubMed: 32162166
DOI: 10.1007/s10072-020-04303-x -
The Medical Letter on Drugs and... Apr 2015
Review
Topics: Animals; Antiparkinson Agents; Capsules; Carbidopa; Clinical Trials as Topic; Delayed-Action Preparations; Drug Combinations; Humans; Levodopa; Parkinson Disease
PubMed: 25897548
DOI: No ID Found -
The American Journal of Medicine Jan 2021Age-related macular degeneration (AMD) is a common cause of blindness worldwide. Neovascular AMD (nAMD) is an advanced form of the disease, in which excess vascular...
BACKGROUND
Age-related macular degeneration (AMD) is a common cause of blindness worldwide. Neovascular AMD (nAMD) is an advanced form of the disease, in which excess vascular endothelial growth factor (VEGF) induces growth of new blood vessels that leak fluid, accounting for 90% of vision loss in AMD. Dysfunction of the retinal pigment epithelium likely initiates AMD. Retinal pigment epithelial cells express a G protein-coupled receptor, GPR143, which downregulates VEGF in response to levodopa. Anti-VEGF therapy effectively treats nAMD, suggesting that excessive VEGF activity drives the pathology.
METHODS
In an open-label pilot study, in patients with newly diagnosed nAMD and naïve to anti-VEGF injections (Cohort-1), the effects of carbidopa-levodopa on vision and anatomic outcomes were evaluated for 4 weeks. Then patients were followed 5 months further with ascending levodopa doses. Patients previously treated with anti-VEGF injection therapy (Cohort-2) were also treated with ascending levodopa doses and evaluated for 6 months.
RESULTS
Levodopa was safe, well tolerated, and delayed anti-VEGF injection therapy while improving visual outcomes. In the first month, retinal fluid decreased by 29% (P = .02, n = 12) without anti-VEGF treatment. Through 6 months the decrease in retinal fluid was sustained, with a mean frequency of 0.38 injections/month. At month 6, mean visual acuity improved by 4.7 letters in Cohort-1 (P = .004, n = 15) and by 4.8 letters in Cohort-2 (P = .02, n = 11). Additionally, there was a 52% reduction in the need for anti-VEGF injections in Cohort-2 (P = .002).
CONCLUSIONS
Our findings suggest efficacy and support the pharmacological targeting of GPR143 with levodopa for the treatment of nAMD in future studies.
Topics: Aged; Aged, 80 and over; Carbidopa; Cohort Studies; Dopamine Agents; Drug Combinations; Female; Humans; Levodopa; Macular Degeneration; Male; Middle Aged; Pilot Projects; Treatment Outcome
PubMed: 32628915
DOI: 10.1016/j.amjmed.2020.05.038 -
Expert Opinion on Drug Delivery 2023Parkinson's disease (PD) is the second most common neurodegenerative disease and is growing in prevalence and disability. The standard treatment for PD is oral levo-dopa... (Review)
Review
INTRODUCTION
Parkinson's disease (PD) is the second most common neurodegenerative disease and is growing in prevalence and disability. The standard treatment for PD is oral levo-dopa (LD) with carbidopa (CD). As PD progresses, despite higher doses of LD/CD, plasma levels of LD fluctuate, and may be associated with motor fluctuations and dyskinesia.
AREAS COVERED
The development of two new subcutaneous preparations of LD/CD (ND0612 and ABBV-951) for the treatment of motor fluctuations in PD is described in detail. Both reduce motor fluctuations and dyskinesia with minor infusion site adverse events. A third subcutaneous preparation, DIZ102, is in early-stage development.
EXPERT OPINION
The premise for using continuous release LD in advanced PD is that steady state levels of LD will prevent motor fluctuations/dyskinesia, but this is not the whole story, and will limit the benefits of subcutaneous continuous release LD. With its present pump system ND0612 cannot be used as monotherapy, whereas ABBV-951 can be. Having to combine with oral LD/CD will complicate the use of ND0612. Both ND0612 and ABBV-951 only cause modest reductions in OFF time. It is not clear whether these subcutaneous preparations will have more benefits than the intestinal gel, which also reduces OFF time and dyskinesia.
Topics: Humans; Carbidopa; Levodopa; Parkinson Disease; Neurodegenerative Diseases; Drug Combinations; Dyskinesias; Antiparkinson Agents
PubMed: 37634938
DOI: 10.1080/17425247.2023.2253146 -
Expert Opinion on Pharmacotherapy 2016Parkinson's disease (PD) is one of the most challenging neurodegenerative disorders to treat as it manifests with a large variety of troublesome, and often disabling,... (Review)
Review
INTRODUCTION
Parkinson's disease (PD) is one of the most challenging neurodegenerative disorders to treat as it manifests with a large variety of troublesome, and often disabling, motor and non-motor symptoms. Despite limitations, such as motor and other complications, levodopa remains the most effective drug in the treatment of PD.
AREAS COVERED
In this review, we focus on phase 2 and 3 studies describing new and emerging medical therapies in PD. We discuss new formulations of levodopa, medications that prolong levodopa response and ameliorate levodopa-induced dyskinesias, and innovative delivery methods that are currently being evaluated in clinical trials or are in development with the promise of better efficacy and tolerability. We also describe novel non-dopaminergic drugs that have been identified for treatment of motor and non-motor symptoms. A specific section is designated for potential disease modifying therapies.
EXPERT OPINION
Alternative formulations of levodopa appear to be promising especially to help with the motor fluctuations either by providing sustained benefits with controlled released formulations or ameliorate sudden OFF by formulations such as inhaled levodopa. Several different medications affecting non-dopaminergic pathways are being evaluated which may aide levodopa. As the understanding of the disease grows further, numerous novel neuroprotective or disease modifying therapies have been suggested. This along with development of medications to treat various non-motor symptoms will help improve quality of life of patients with PD.
Topics: Antiparkinson Agents; Carbidopa; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Drug Administration Routes; Drug Therapy, Combination; Humans; Levodopa; Parkinson Disease; Quality of Life
PubMed: 26830844
DOI: 10.1517/14656566.2016.1149163 -
Parkinsonism & Related Disorders Apr 2022The objective of this study was to compare the pharmacokinetics (PK) of levodopa (LD) from 24-h continuous subcutaneous infusion of foslevodopa/foscarbidopa to the LD... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
The objective of this study was to compare the pharmacokinetics (PK) of levodopa (LD) from 24-h continuous subcutaneous infusion of foslevodopa/foscarbidopa to the LD pharmacokinetics from 16-h levodopa-carbidopa intestinal gel (LCIG) followed by night-time oral LD/carbidopa (CD) doses.
METHODS
This was a Phase 1, open-label, randomized, 2-period crossover study conducted in 25 male and female healthy volunteers.
RESULTS
The LD exposures (C, AUC and AUC∞) following subcutaneous infusion of 700/35 mg foslevodopa/foscarbidopa over 24 h were similar (<8% difference) to those of LCIG 350/87.5 mg LD/CD administered over 16 h followed by two 100/25 mg LD/CD oral doses at 18 and 21 h after the start of LCIG delivery.
CONCLUSION
Foslevodopa/foscarbidopa subcutaneous infusion provides levodopa exposures comparable to LCIG throughout the day.
GOV IDENTIFIER
Not Applicable.
Topics: Antiparkinson Agents; Carbidopa; Cross-Over Studies; Dopamine Agonists; Drug Combinations; Female; Gels; Humans; Infusions, Subcutaneous; Jejunum; Levodopa; Male; Parkinson Disease
PubMed: 35339102
DOI: 10.1016/j.parkreldis.2022.03.012 -
Movement Disorders : Official Journal... Apr 2023Long-duration response (LDR) to levodopa and motor learning could be involved in changes in neuroplasticity of cortical excitability in Parkinson's disease (PD). P300,...
BACKGROUND
Long-duration response (LDR) to levodopa and motor learning could be involved in changes in neuroplasticity of cortical excitability in Parkinson's disease (PD). P300, motor evoked potentials (MEPs), and Bereitschaftspotential (BP) are neurophysiological surrogate markers of neuroplasticity.
OBJECTIVE
We aimed to define in PD the effects of LDR and motor learning on neurophysiological parameters involved in neuroplasticity.
METHODS
Drug-naive PD patients underwent a 15-day treatment with levodopa/carbidopa 250/25 mg daily. Achievement of LDR was assessed on the 15th day of treatment (T15). Patients were grouped based on the achievement of a sustained LDR (LDR+) or no LDR (LDR-) and to the assignment of a learning motor exercise (LME) or no motor exercise (NME). Patients underwent clinical and neurophysiological (P300, MEPs, and BP) assessments at baseline (T0) and on T15.
RESULTS
Forty-one PD patients and 24 age- and sex-matched normal controls (NCs) were enrolled. Neurophysiological parameters differed between untreated PD patients and NCs. Four groups of patients were obtained at the end of treatments: trained patients with a sustained LDR (LDR + LME group), untrained patients with a sustained LDR (LDR + NME group), trained patients without LDR (LDR-LME group), and untrained patients without LDR (LDR-NME group). At baseline, no differences in clinical and neurophysiological parameters were evident among the groups. After the treatments, significant improvements in neurophysiological parameters were observed in the LDR + LME group. No modifications were found in the groups without LDR.
CONCLUSIONS
The achievement of a sustained LDR may act synergistically with motor learning to induce adaptive changes in neuroplasticity in basal ganglia and cortical networks. Our findings support LDR as a pharmacological outcome possibly facilitating the action of motor learning on neuroplasticity in early PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Humans; Levodopa; Parkinson Disease; Carbidopa; Time Factors; Learning; Antiparkinson Agents
PubMed: 36840442
DOI: 10.1002/mds.29344 -
CNS Drugs Dec 2022Research comparing levodopa/carbidopa intestinal gel (LCIG), deep brain stimulation (DBS), and continuous subcutaneous apomorphine infusion (CSAI) for advanced... (Meta-Analysis)
Meta-Analysis
Comparative Effectiveness of Device-Aided Therapies on Quality of Life and Off-Time in Advanced Parkinson's Disease: A Systematic Review and Bayesian Network Meta-analysis.
INTRODUCTION
Research comparing levodopa/carbidopa intestinal gel (LCIG), deep brain stimulation (DBS), and continuous subcutaneous apomorphine infusion (CSAI) for advanced Parkinson's disease (PD) is lacking. This network meta-analysis (NMA) assessed the comparative effectiveness of LCIG, DBS, CSAI and best medical therapy (BMT) in reducing off-time and improving quality of life (QoL) in patients with advanced PD.
METHODS
A systematic literature review was conducted for randomized controlled trials (RCTs), observational and interventional studies from January 2003 to September 2019. Data extracted at baseline and 6 months were off-time, as reported by diary or Unified Parkinson's Disease Rating Scale Part IV item 39, and QoL, as reported by Parkinson's Disease Questionnaire (PDQ-39/PDQ-8). Bayesian NMA was performed to estimate pooled treatment effect sizes and to rank treatments in order of effectiveness.
RESULTS
A total of 22 studies fulfilled the inclusion criteria (n = 2063 patients): four RCTs, and 16 single-armed, one 2-armed and one 3-armed prospective studies. Baseline mean age was between 55.5-70.9 years, duration of PD was 9.1-15.3 years, off-time ranged from 5.4 to 8.7 h/day in 9 studies, and PDQ scores ranged from 28.8 to 67.0 in 19 studies. Levodopa/carbidopa intestinal gel and DBS demonstrated significantly greater improvement in off-time and QoL at 6 months compared with CSAI and BMT (p < 0.05). There was no significant difference in the effects of LCIG and DBS, but DBS was ranked first for reduction in off-time, and LCIG was ranked first for improvement in QoL.
CONCLUSIONS
This NMA found that LCIG and DBS were associated with superior improvement in off-time and PD-related QoL compared with CSAI and BMT at 6 months after treatment initiation. This comparative effectiveness research may assist providers, patients, and caregivers in the selection of the optimal device-aided therapy.
Topics: Humans; Middle Aged; Aged; Carbidopa; Levodopa; Quality of Life; Network Meta-Analysis; Parkinson Disease; Apomorphine
PubMed: 36414908
DOI: 10.1007/s40263-022-00963-9