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Cognitive Aging Parkinson’s Disease
Applicability and Benefit of Enteral Levodopa/Carbidopa Infusion in
Advanced Parkinson’s Disease
a report by
Francesc Valldeoriola, MD, PhD
Consultant Neurologist, Movement Disorders Unit, Institute of Neurosciences, University of Barcelona
Parkinson’s disease (PD) is a devastating, progressive disorder that A three-week open, randomized, cross-over study comparing the variability
responds favorably to therapeutic doses of levodopa, its gold standard in plasma concentrations of sustained-release levodopa and Duodopa
therapy. The phase of the disease (early, middle, or advanced) largely infusion in 12 patients with motor complications showed marked
determines the type of treatment. Initially, there is good response to improvement of fluctuations and increased on-time without dyskinesias
medication and adjuvant therapeutic strategies but, after several years, during the infusion.
2
Another study
3
demonstrated increased on-time (mean
motor and non-motor complications develop. These are produced in part 4.5 hours); situations of moderate to severe parkinsonism virtually
owing to erratic gastric emptying, leading to irregular absorption and disappeared in patients who received the infusion compared with those
fluctuating plasma levels of levodopa, and hence an unstable response. At who were treated with optimized oral medication.
this point, clinical fluctuations are gradually more difficult to control and,
therefore, patients’ quality of life deteriorates. In recent years, the Several studies of long-term effectiveness have also been published. In a
development of subthalamic and pallidal deep brain stimulation (DBS) for retrospective open study,
4
28 patients with early onset of the disease and
the treatment of these long-term PD complications has been a major step prolonged time of evolution were treated with Duodopa for up to seven
forward. There is good evidence that DBS can reduce the difference years. The reason for infusion was in all cases related to motor fluctuations.
between off and on states and that the benefit achievable with DBS can The average daily intake of levodopa was reduced slightly by infusion
be predicted by the levodopa response. Nevertheless, the clinical reality is compared with oral therapy. At the end of the study, continuous infusion
that DBS does not reach the theoretical maximum effect in everyone. continued to maintain the benefit with respect to the oral therapy in terms
Patient selection and electrode location have a huge impact on the of increased on-time. Another retrospective long-term study
5
was conducted
outcome, as does the experience of the surgeon. Adverse effects derived through a structured review of medical records of all patients who had
from the neurosurgical procedure are uncommon, but the so-called received enteral carbidopa/levodopa infusion during the period 1991–2002.
hardware complications produced by fractures, disruptions, or infections All patients had advanced PD with dyskinesias and motor fluctuations. About
of the implanted system are relatively frequent. Psychiatric symptoms after 75% of patients remained in enteric infusion of levodopa for at least two
subthalamic stimulation have also been repeatedly described in the years, with about 50% receiving infusion for at least six years.
medical literature. Moreover, a recent study demonstrated that only about
1.6–4.5% of patients are suitable for DBS.
1
Several prospective studies have also evaluated the efficacy of this therapy:
an Italian survey
6
on nine patients with advanced PD showed a remarkable
In recent years, a novel gel form of levodopa/carbidopa (Duodopa
®
) has reduction of the duration of the off-periods and important amelioration of
enabled infusion through percutaneous endoscopic gastrostomy (PEG) disabling dyskinesias. Activities of daily living scores markedly improved;
directly into the duodenum. This system avoids the gastric step, hence quality of life, as measured through standard scales such as the PDQ-39
enhancing absorption of the drug and favoring stable plasma levels of (specific for PD), was also ameliorated in all patients.
levodopa. Duodopa has been approved in all EU countries plus Norway,
Switzerland, and Canada. This is a treatment system for people who are Furthermore, a survey in five patients showed the usefulness of duodenal
in an advanced stage of the disease. Dosing of Duodopa is adjusted to infusions during the night hours in patients with severe nocturnal
the needs of each individual patient and is delivered continuously Parkinsonian symptoms. Tolerance phenomena or increase of the occurrence
throughout the day. Duodopa is used as monotherapy. This method of of dyskinesias and hallucinations were not observed.
continuous dopaminergic stimulation may give better control of the
symptoms compared with traditional oral medication. It is given inside
Francesc Valldeoriola, MD, PhD, is a Consultant in Neurology at
the upper intestine via a small tube inserted directly into the first part of
the Parkinson’s Disease and Movement Disorders Unit at the
the small bowel, or duodenum. The unique delivery system, with a Institut Clínic de Neurociències, Hospital Clínic i Provincial,
programmable pump, allows the physician and patient to individually
Barcelona. He is a member of the Spanish Neurological Society
and European Neurological Society. He obtained his doctorate and
tune the delivery of active ingredients, suspended as stable gel from a
MD from the University of Barcelona, with other positions at
cassette worn outside the body. Better control of body movements can Emory University in Atlanta and Northwestern Hospital in Toronto.
be achieved, resulting in many patients becoming more functional in
E:
fvallde@clinic.ub.es
their daily lives. The advantages of this approach have since been
considered in several clinical studies.
© TOUCH BRIEFINGS 2008
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