Evidence map›Paper›PMID 36229860›Full record

ReviewTranslational neurodegeneration2022

Why do 'OFF' periods still occur during continuous drug delivery in Parkinson's disease?

Silvia Rota, Daniele Urso, Daniel J van Wamelen, Valentina Leta, Iro Boura, Per Odin, Alberto J Espay, Peter Jenner, K Ray Chaudhuri

Open access · goldAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Translational neurodegeneration, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.2field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 20 citations in OpenAlex.

  1. Trial
  2. Review
  3. Review
  4. Article
  5. Review
  6. Levodopa treatment: impacts and mechanisms throughout Parkinson's disease progression.Journal of neural transmission (Vienna, Austria : 1996) · 2025
    Review
  7. Article
  8. Observational
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 6 countries.

Silvia RotaDepartment of Basic and Clinical Neurosciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. silvia.rota@kcl.ac.uk.ORCID 0000-0001-8281-9797
Daniele UrsoDepartment of Basic and Clinical Neurosciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Daniel J van WamelenDepartment of Basic and Clinical Neurosciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Valentina LetaDepartment of Basic and Clinical Neurosciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Iro BouraDepartment of Basic and Clinical Neurosciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Per OdinDivision of Neurology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
Alberto J EspayUniversity of Cincinnati Gardner Neuroscience Institute, Gardner Family Center for Parkinson's Disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH, USA.
Peter JennerInstitute of Pharmaceutical Sciences, Faculty of Life Science and Medicine, King's College London, London, UK. peter.jenner@kcl.ac.uk.
K Ray ChaudhuriDepartment of Basic and Clinical Neurosciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
King's College London · GBLund University · SERadboud University Nijmegen · NLUniversity of Cincinnati · USUniversity of Crete · GR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

CarbidopaParkinson DiseaseAntiparkinson AgentsApomorphineDopamineHumansLevodopaAntiparkinson AgentsApomorphineCarbidopaDopamineLevodopaContinuous dopaminergic stimulationContinuous drug deliveryLevodopa-carbidopa intestinal gel‘OFF’ periodsRotigotine patchSubcutaneous apomorphine infusion

Identifiers

PMID36229860
PMCPMC9558383
OpenAlexW4304890827

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.