Long-term outcome of Duodenal Levodopa Infusion for Advanced Parkinson’s Disease

Long-term outcome of Duodenal Levodopa Infusion for Advanced Parkinson’s Disease
Antonini Angelo
SOLVAY PHARMACEUTICALS - EUROPEAN NEUROLOGICAL DISEASE 2007 SUPPLEMENT
Published: August 2007
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Abstract
Motor fluctuations and dyskinesias in Parkinson’s disease (PD) patients cause severe disability and may not be adequately controlled by oral treatment. Longterm therapy options include deep brain stimulation (DBS) and apomorphine infusions. However, DBS is associated with neuropsychiatric complications and is suitable for only a small percentage of PD patients, and apomorphine infusion has no effect on dyskinesias and in our experience has a high drop-out rate. Infusion with levodopa on its own is not feasible as the drug is poorly soluble in water. In recent years, a novel gel form of levodopa plus carbidopa has been developed, enabling infusion directly into the duodenum through percutaneous endoscopic gastrostomy. Continuous levodopa infusion in this manner should overcome the problems of fluctuations caused by pulsatile oral therapy. Our experience with Duodopa, reported here, includes 14 patients – nine of whom remained at two-year follow-up – and showed that, with continuous therapy, the total amount of levodopa administered to patients is relatively constant, and a therapeutic window could be established. The majority of adverse events were related to the procedure and hardware. Levodopa duodenal infusion improved motor fluctuations and reduced disabling dyskinesias, resulting in significant benefits in quality of life. Our results demonstrate that a satisfactory therapeutic window can be achieved and maintained for more than two years in advanced PD patients using this treatment.

There are many reasons why a clinical neurologist might be concerned about treatment of advanced Parkinson’s disease (PD). Of the current options available, ergot-derived dopamine agonists can cause significant adverse events, such as impulse control disorders1–3 and heart valve abnormalities;4–6 apomorphine infusion is associated with skin reactions;7,8 and deep brain stimulation of the subthalamic nucleus (STN-DBS), which is suitable for fewer than 3% of PD patients, is associated with behavioural and cognitive abnormalities9–11 and does not improve quality of life in patients older than 65 years, who represent the majority of PD patients.11

Long-term Treatment Options
STN-DBS has proved effective in providing significant clinical improvement in advanced PD patients. Indeed, STN-DBS is associated with a eduction in dopaminergic medications and ‘off’ time improvement. However, chronic use has been associated with a significant worsening of neuropsychiatric scales, resulting in long-term behavioural problems in some patients.11 Moreover, this management option is not suitable for many advanced PD patients. A recent survey conducted in Italy attempted to establish the number of patients suitable for STN-DBS. Of 641 consecutive patients seen over one month, only 1.6% fulfilled the strict inclusion criteria of the core assessment programme for surgical interventional therapies in PD (CAPSIT-PD).10 It is interesting to note that in this study 60% of patients were excluded because they failed to satisfy multiple criteria, while 20 patients were excluded for only one criterion. Criteria related to disease severity were responsible for the largest number of exclusions. By employing more flexible criteria – allowing patients with Unified Parkinson Disease Rating Scale (UPDRS) ‘off’ scores above 40, for example – the inclusion percentage can be raised to 3.7%. Including those with active psychiatric symptoms raised it to 4.5%. Therefore, while DBS is an interesting and relatively successful procedure, it cannot be applied in the large majority of cases.

Keywords:
Duodenal Levodopa Infusion, Parkinson’s Disease,

References:
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