Cargando…
Why do ‘OFF’ periods still occur during continuous drug delivery in Parkinson’s disease?
Continuous drug delivery (CDD) is used in moderately advanced and late-stage Parkinson’s disease (PD) to control motor and non-motor fluctuations (‘OFF’ periods). Transdermal rotigotine is indicated for early fluctuations, while subcutaneous apomorphine infusion and levodopa-carbidopa intestinal gel...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9558383/ https://www.ncbi.nlm.nih.gov/pubmed/36229860 http://dx.doi.org/10.1186/s40035-022-00317-x |
_version_ | 1784807432803844096 |
---|---|
author | Rota, Silvia Urso, Daniele van Wamelen, Daniel J. Leta, Valentina Boura, Iro Odin, Per Espay, Alberto J. Jenner, Peter Chaudhuri, K. Ray |
author_facet | Rota, Silvia Urso, Daniele van Wamelen, Daniel J. Leta, Valentina Boura, Iro Odin, Per Espay, Alberto J. Jenner, Peter Chaudhuri, K. Ray |
author_sort | Rota, Silvia |
collection | PubMed |
description | Continuous drug delivery (CDD) is used in moderately advanced and late-stage Parkinson’s disease (PD) to control motor and non-motor fluctuations (‘OFF’ periods). Transdermal rotigotine is indicated for early fluctuations, while subcutaneous apomorphine infusion and levodopa-carbidopa intestinal gel are utilised in advanced PD. All three strategies are considered examples of continuous dopaminergic stimulation achieved through CDD. A central premise of the CDD is to achieve stable control of the parkinsonian motor and non-motor states and avoid emergence of ‘OFF’ periods. However, data suggest that despite their efficacy in reducing the number and duration of ‘OFF’ periods, these strategies still do not prevent ‘OFF’ periods in the middle to late stages of PD, thus contradicting the widely held concepts of continuous drug delivery and continuous dopaminergic stimulation. Why these emergent ‘OFF’ periods still occur is unknown. In this review, we analyse the potential reasons for their persistence. The contribution of drug- and device-related involvement, and the problems related to site-specific drug delivery are analysed. We propose that changes in dopaminergic and non-dopaminergic mechanisms in the basal ganglia might render these persistent ‘OFF’ periods unresponsive to dopaminergic therapy delivered via CDD. |
format | Online Article Text |
id | pubmed-9558383 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-95583832022-10-14 Why do ‘OFF’ periods still occur during continuous drug delivery in Parkinson’s disease? Rota, Silvia Urso, Daniele van Wamelen, Daniel J. Leta, Valentina Boura, Iro Odin, Per Espay, Alberto J. Jenner, Peter Chaudhuri, K. Ray Transl Neurodegener Review Continuous drug delivery (CDD) is used in moderately advanced and late-stage Parkinson’s disease (PD) to control motor and non-motor fluctuations (‘OFF’ periods). Transdermal rotigotine is indicated for early fluctuations, while subcutaneous apomorphine infusion and levodopa-carbidopa intestinal gel are utilised in advanced PD. All three strategies are considered examples of continuous dopaminergic stimulation achieved through CDD. A central premise of the CDD is to achieve stable control of the parkinsonian motor and non-motor states and avoid emergence of ‘OFF’ periods. However, data suggest that despite their efficacy in reducing the number and duration of ‘OFF’ periods, these strategies still do not prevent ‘OFF’ periods in the middle to late stages of PD, thus contradicting the widely held concepts of continuous drug delivery and continuous dopaminergic stimulation. Why these emergent ‘OFF’ periods still occur is unknown. In this review, we analyse the potential reasons for their persistence. The contribution of drug- and device-related involvement, and the problems related to site-specific drug delivery are analysed. We propose that changes in dopaminergic and non-dopaminergic mechanisms in the basal ganglia might render these persistent ‘OFF’ periods unresponsive to dopaminergic therapy delivered via CDD. BioMed Central 2022-10-13 /pmc/articles/PMC9558383/ /pubmed/36229860 http://dx.doi.org/10.1186/s40035-022-00317-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Review Rota, Silvia Urso, Daniele van Wamelen, Daniel J. Leta, Valentina Boura, Iro Odin, Per Espay, Alberto J. Jenner, Peter Chaudhuri, K. Ray Why do ‘OFF’ periods still occur during continuous drug delivery in Parkinson’s disease? |
title | Why do ‘OFF’ periods still occur during continuous drug delivery in Parkinson’s disease? |
title_full | Why do ‘OFF’ periods still occur during continuous drug delivery in Parkinson’s disease? |
title_fullStr | Why do ‘OFF’ periods still occur during continuous drug delivery in Parkinson’s disease? |
title_full_unstemmed | Why do ‘OFF’ periods still occur during continuous drug delivery in Parkinson’s disease? |
title_short | Why do ‘OFF’ periods still occur during continuous drug delivery in Parkinson’s disease? |
title_sort | why do ‘off’ periods still occur during continuous drug delivery in parkinson’s disease? |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9558383/ https://www.ncbi.nlm.nih.gov/pubmed/36229860 http://dx.doi.org/10.1186/s40035-022-00317-x |
work_keys_str_mv | AT rotasilvia whydooffperiodsstilloccurduringcontinuousdrugdeliveryinparkinsonsdisease AT ursodaniele whydooffperiodsstilloccurduringcontinuousdrugdeliveryinparkinsonsdisease AT vanwamelendanielj whydooffperiodsstilloccurduringcontinuousdrugdeliveryinparkinsonsdisease AT letavalentina whydooffperiodsstilloccurduringcontinuousdrugdeliveryinparkinsonsdisease AT bourairo whydooffperiodsstilloccurduringcontinuousdrugdeliveryinparkinsonsdisease AT odinper whydooffperiodsstilloccurduringcontinuousdrugdeliveryinparkinsonsdisease AT espayalbertoj whydooffperiodsstilloccurduringcontinuousdrugdeliveryinparkinsonsdisease AT jennerpeter whydooffperiodsstilloccurduringcontinuousdrugdeliveryinparkinsonsdisease AT chaudhurikray whydooffperiodsstilloccurduringcontinuousdrugdeliveryinparkinsonsdisease |