scholarly journals The catechol-O-methyltransferase (COMT) inhibitor entacapone enhances the pharmacokinetic and clinical response to Sinemet CR in Parkinson's disease

2000 ◽  
Vol 68 (5) ◽  
pp. 589-594 ◽  
Author(s):  
P. Piccini
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Response ◽  
Comt Inhibitor

The effects of cisapride on plasmaL-dopa levels and clinical response in Parkinson's disease

1995 ◽  
Vol 10 (1) ◽  
pp. 66-70 ◽  
Author(s):  
Walter Diaz Neira ◽  
Vicenta Sanchez ◽  
Maria Angeles Mena ◽  
Justo Garcia de Yebenes
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Response

COMT Inhibitors: Novel Treatments for Parkinson's Disease

CNS Spectrums ◽  
1998 ◽  
Vol 3 (2) ◽  
pp. 53-56 ◽  
Author(s):  
Charles H. Adler
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Comt Inhibitors ◽  
Novel Treatments ◽  
New Class ◽  
Comt Inhibitor ◽  
Duration Of Response

AbstractCatechol-O-methyltransferase (COMT) inhibitors are a new class of medication being developed for the treatment of Parkinson's disease (PD). The enzyme COMT metabolizes levodopa and dopamine, both peripherally and centrally. Coadministration of a COMT inhibitor with levodopa creates an increase in peripheral and central levodopa bioavailability, as well as higher central dopamine concentrations. Because these actions improve the duration of response to levodopa, the COMT inhibitors should prove to be useful adjunctive therapies in PD patients.

18F-dopa PET evidence that tolcapone acts as a central COMT inhibitor in Parkinson's disease

Synapse ◽  
2002 ◽  
Vol 43 (3) ◽  
pp. 201-207 ◽  
Author(s):  
Roberto Ceravolo ◽  
Paola Piccini ◽  
Dale L. Bailey ◽  
Karin M. Jorga ◽  
Helen Bryson ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Comt Inhibitor

Utilization of Quantitative Susceptibility Mapping for Direct Targeting of the Subthalamic Nucleus During Deep Brain Stimulation Surgery

2017 ◽  
Vol 14 (4) ◽  
pp. 412-419 ◽  
Author(s):  
Jonathan Rasouli ◽  
Ritesh Ramdhani ◽  
Fedor E Panov ◽  
Alexey Dimov ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Clinical Response ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Quantitative Susceptibility Mapping ◽  
Direct Targeting ◽  
Satisfactory Clinical Response ◽  
Deep Brain

AbstractBACKGROUNDDeep brain stimulation of the subthalamic nucleus (STN) has demonstrated efficacy in improving motor disability in Parkinson's disease. The recently developed quantitative susceptibility mapping (QSM) technique, which can accurately map iron deposits in deep brain nuclei, promises precise targeting of the STN.OBJECTIVETo demonstrate the use of QSM to target STN effectively by correlating with classical physiological-based targeting measures in a prospective study.METHODSThe precision and accuracy of direct targeting with QSM was examined in a total of 25 Parkinson's disease patients between 2013 and 2015 at our institution. QSM was utilized as the primary magnetic resonance imaging (MRI) method to perform direct STN targeting on a stereotactic planning station utilizing computed tomography/MR fusion. Intraoperative microelectrode recordings (MER) were obtained to confirm appropriate trajectory through the sensorimotor STN.RESULTSEstimations of STN thickness between the MER and QSM methods appeared to be correlated. Mean STN thickness was 5.3 mm. Kinesthetic responsive cells were found in > 90% of electrode runs. The mean radial error (±SEM) was 0.54 ± 0.1 mm. Satisfactory clinical response as determined by Unified Parkinson's Disease Rating Scale (UPDRS III) was seen at 12 mo after surgery.CONCLUSIONDirect targeting of the sensorimotor STN using QSM demonstrates MER correlation and can be safely used for deep brain stimulation lead placement with satisfactory clinical response. These results imply that targeting based on QSM signaling alone is sufficient to obtain reliable and reproducible outcomes in the absence of physiological recordings.

3 The dopaminergic balancing act: a literature review of a novel COMT inhibitor opicapone with a focus on the risk of visual hallucinations

2020 ◽  
Vol 91 (8) ◽  
pp. e9.2-e9
Author(s):  
Richard Cole ◽  
Romi Saha
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Literature Review ◽  
Observational Studies ◽  
Neuropsychiatric Symptoms ◽  
Psychiatric History ◽  
Visual Hallucinations ◽  
Post Hoc Analysis ◽  
Comt Inhibitor ◽  
Post Hoc

AimsParkinson’s Disease (PD) medications are well-evidenced for improving motor symptoms. However, often a balancing act is required to ameliorate positive neuropsychiatric symptoms, such as visual hallucinations (VH). Opicapone, a novel COMT inhibitor, has been shown by BIPARK-1 and BIPARK-2 studies to improve wearing-off phenomena but little is known about associated neuropsychiatric symptoms. The aim of this literature review was to investigate any association between opicapone and VH.MethodsA literature review was undertaken on the 18th July 2019 using PubMed, Ovid (using key resources of Embase, Ovid MEDLINE, Global Health and PsycINFO), Web of Science and Scopus. The search terms used were ‘Parkinson’s Disease’ and ‘Opicapone’. The search included full-texts, abstracts, conference abstracts and posters.ResultsThe initial search produced 398 articles; 391 were excluded. Of the 7 articles reviewed there were two randomised controlled trials (RCTs) (BIPARK-1 and -2), two observational studies, two post-hoc analyses of BIPARK-1 and -2, and one retrospective analysis. BIPARK-1 reported VH in 1% of the entacapone group, 8% opicapone 25 mg group and 4% of the opicapone 50 mg group. BIPARK-2 did not report on VH in their randomised phased and reported VH in 0.8% of opicapone patients in their open-label phase but without specifying the associated dose.Chaudhuri et al.’s (2018) post-hoc analysis of BIPARK-1 reported VH in 8% of COMT- naive patients given opicapone, vs. 1% of those given entacapone. Lees et al.’s (2019) post-hoc analysis of BIPARK-1 & -2 reported VH in 4.6% of patients receiving opicapone who were ≥70 years old, vs 0.6% in those younger. Gandor et al.’s (2018) prospective observational study reported VH in 14.8% of patients given opicapone.ConclusionsSeveral factors limit the conclusions drawn about the risk of VH in patients taking opicapone. The RCTs were designed and powered to assess ‘on-off’ phenomena and didn’t include patients >65 or with a psychiatric history. This also limits their post-hoc analyses’ generalisability. The more ‘real-world’ observational studies were small and only available in abstract form with limited details. Lees et al.’s (2019) post-hoc analysis nevertheless reported a higher incidence of VH in the older age group, which is concordant with known risk factors for neuropsychiatric adverse events. Further investigation is required, focusing on older patients and those with a psychiatric history or cognitive impairment.

scholarly journals 152 Pimavanserin for the Treatment of Parkinson’s Disease Psychosis: Number Needed to Treat, Number Needed to Harm, and Likelihood to Be Helped or Harmed

CNS Spectrums ◽  
2018 ◽  
Vol 23 (1) ◽  
pp. 94-95
Author(s):  
Leslie Citrome ◽  
James Norton ◽  
Kathy Chi-Burris ◽  
George Demos
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Adverse Event ◽  
Clinical Response ◽  
Fixed Dose ◽  
Number Needed To Treat ◽  
Double Blind ◽  
Term Care ◽  
Study Objective ◽  
Number Needed To Harm

AbstractStudy ObjectivePsychosis is common in Parkinson’s disease (PD) and increases in both frequency and severity with disease duration. It is associated with increased morbidity/mortality, complicates management of motor symptoms and often leads to long-term care placement. Pimavanserin (PIM) is a highly selective serotonin 5-HT2A receptor antagonist/inverse agonist indicated for the treatment of hallucinations and delusions associated with PD psychosis (PDP). The study aim is to review theevidence-base for PIM for the treatment of PDP using the metrics of evidence-based medicine, namely number needed to treat (NNT), number needed to harm (NNH), andlikelihood to be helped or harmed (LHH), in order to better place this intervention into clinical perspective.MethodsNNT and NNH are measures of effect size and indicate how many patients would need to be treated with one agent instead of the comparator in order to encounter one additional outcome of interest. A useful medication is one with a low NNT and a high NNH when comparing it with another intervention; a low NNT and a high NNH would mean one is more likely to encounter a benefit than a harm. Categorical efficacy and tolerability data was extracted from the clinical trial databases of the double-blind placebo-controlled studies of PIM in persons with PDP. The studies were 6 weeks in duration and fixed dose with the exception of study ACP-103-006 which was 4-weeks in duration. NNT and NNH values were calculated with their respective 95% confidence intervals. Efficacy endpoints were defined based on 2 definitions: a) Scale for the Assessment ofPositive Symptoms in Parkinson’s Disease (SAPS-PD) total score decrease ≥3 points from baseline and b) Clinical Global Impressions-Improvement scale (CGI-I) score of 1 (very much improved) or 2 (much improved). Tolerability outcomes of clinical interest, occurring at any time in available studies were assessed, including discontinuation due toan adverse event (AE). Likelihood to be helped or harmed (LHH) was then calculated contrasting therapeutic response vs. discontinuation because of an AE.ResultsNNT values for PIM 34 mg/d vs. placebo for several definitions of clinical response are <10, and as robust as 4, denoting that PIM is a potentially efficacious intervention. NNH values for tolerability outcomes for PIM 34 mg/d (as well as for doses that range from 8.5 mg/d to 51 mg/d) are >10, and/or are not statistically significant, and/or show an advantage for PIM over placebo (such as for postural hypotension), denoting that PIM is a potentially tolerable intervention. In terms of LHH, PIM 34 mg/d is about 5 times more likely to result in clinical response (as measured by ≥3 point decrease from baseline on the SAPS-PD) vs. discontinuation due to an adverse event.ConclusionsUsing the metrics of NNT, NNH, and LHH, PIM 34 mg/d for the treatment of PDP appears to have a compelling benefit-risk profile.Funding AcknowledgementsClinical study was funded by ACADIA Pharmaceuticals Inc.

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