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Levodopa--carbidopa intestinal gel for treatment of advanced Parkinson''s disease

Fernandez, H. H. and Odin, Per LU (2011) In Current Medical Research and Opinion 27(5). p.907-919
Abstract
Levodopa is the mainstay of Parkinson''s disease (PD) treatment, but is often eventually associated with disabling motor complications in patients with advanced PD. The inability of perorally administered levodopa to provide more physiologic continuous dopaminergic stimulation (CDS) is a leading hypothesis to explain these complications. To investigate the cumulative efficacy and safety, and re-evaluate the role, of levodopa--carbidopa intestinal gel (LCIG) infusion in treatment of advanced PD patients experiencing levodopa-associated motor complications, through its purported mechanism for providing CDS. Literature searches in the MEDLINE/PubMed database were used to identify peer-reviewed publications examining the role of CDS in... (More)
Levodopa is the mainstay of Parkinson''s disease (PD) treatment, but is often eventually associated with disabling motor complications in patients with advanced PD. The inability of perorally administered levodopa to provide more physiologic continuous dopaminergic stimulation (CDS) is a leading hypothesis to explain these complications. To investigate the cumulative efficacy and safety, and re-evaluate the role, of levodopa--carbidopa intestinal gel (LCIG) infusion in treatment of advanced PD patients experiencing levodopa-associated motor complications, through its purported mechanism for providing CDS. Literature searches in the MEDLINE/PubMed database were used to identify peer-reviewed publications examining the role of CDS in levodopa-associated motor complications and pharmacologic strategies for CDS, focusing on LCIG infusion for advanced PD patients. LCIG, an aqueous gel, is continuously infused (daytime only or 24 h) via a portable pump and tube permanently inserted into the duodenum through percutaneous endoscopic gastrostomy (PEG). LCIG infusion provides stable levodopa plasma levels, which are significantly less variable than those with oral levodopa. Clinical trials indicate LCIG may significantly improve motor complications (reduction of time in ''off'' and time in ''on with dyskinesias''), motor scores using the Unified Parkinson''s Disease Rating Scale (UPDRS), non-motor symptomatology (Non-motor Symptom Scale) and health-related quality of life (HRQOL) in advanced PD patients. The adverse-event profile of LCIG is similar to that of oral levodopa, although technical problems with the infusion device have occurred in up to 70%% of patients. LCIG has demonstrated efficacy in reducing levodopa-associated motor complications in patients with advanced PD, and improving UPDRS and HRQOL scores. Because it involves PEG and its associated risks, LCIG is recommended for patients in whom motor fluctuations and dyskinesias are inadequately treated with traditional peroral medication. For these patients, LCIG can be a valuable alternative to deep brain stimulation (DBS), especially when DBS is contraindicated. These conclusions are limited by the modest number and size of completed randomized, controlled trials of LCIG. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
* dyskinesias * continuous dopaminergic stimulation * levodopa-carbidopa * intestinal gel * motor fluctuations * Parkinson's disease
in
Current Medical Research and Opinion
volume
27
issue
5
pages
907 - 919
publisher
LibraPharm
external identifiers
  • wos:000289528000003
  • scopus:79954520846
ISSN
1473-4877
DOI
10.1185/03007995.2011.560146
language
English
LU publication?
yes
id
72d53e33-3da7-4cde-a099-d567f2adaaab (old id 1965773)
date added to LUP
2011-05-23 14:37:19
date last changed
2017-06-25 03:22:16
@article{72d53e33-3da7-4cde-a099-d567f2adaaab,
  abstract     = {Levodopa is the mainstay of Parkinson''s disease (PD) treatment, but is often eventually associated with disabling motor complications in patients with advanced PD. The inability of perorally administered levodopa to provide more physiologic continuous dopaminergic stimulation (CDS) is a leading hypothesis to explain these complications. To investigate the cumulative efficacy and safety, and re-evaluate the role, of levodopa--carbidopa intestinal gel (LCIG) infusion in treatment of advanced PD patients experiencing levodopa-associated motor complications, through its purported mechanism for providing CDS. Literature searches in the MEDLINE/PubMed database were used to identify peer-reviewed publications examining the role of CDS in levodopa-associated motor complications and pharmacologic strategies for CDS, focusing on LCIG infusion for advanced PD patients. LCIG, an aqueous gel, is continuously infused (daytime only or 24 h) via a portable pump and tube permanently inserted into the duodenum through percutaneous endoscopic gastrostomy (PEG). LCIG infusion provides stable levodopa plasma levels, which are significantly less variable than those with oral levodopa. Clinical trials indicate LCIG may significantly improve motor complications (reduction of time in ''off'' and time in ''on with dyskinesias''), motor scores using the Unified Parkinson''s Disease Rating Scale (UPDRS), non-motor symptomatology (Non-motor Symptom Scale) and health-related quality of life (HRQOL) in advanced PD patients. The adverse-event profile of LCIG is similar to that of oral levodopa, although technical problems with the infusion device have occurred in up to 70%% of patients. LCIG has demonstrated efficacy in reducing levodopa-associated motor complications in patients with advanced PD, and improving UPDRS and HRQOL scores. Because it involves PEG and its associated risks, LCIG is recommended for patients in whom motor fluctuations and dyskinesias are inadequately treated with traditional peroral medication. For these patients, LCIG can be a valuable alternative to deep brain stimulation (DBS), especially when DBS is contraindicated. These conclusions are limited by the modest number and size of completed randomized, controlled trials of LCIG.},
  author       = {Fernandez, H. H. and Odin, Per},
  issn         = {1473-4877},
  keyword      = {* dyskinesias
* continuous dopaminergic stimulation
* levodopa-carbidopa
* intestinal gel
* motor fluctuations
* Parkinson's disease},
  language     = {eng},
  number       = {5},
  pages        = {907--919},
  publisher    = {LibraPharm},
  series       = {Current Medical Research and Opinion},
  title        = {Levodopa--carbidopa intestinal gel for treatment of advanced Parkinson''s disease},
  url          = {http://dx.doi.org/10.1185/03007995.2011.560146},
  volume       = {27},
  year         = {2011},
}