Levodopa is the most efficacious medication for symptomatic treatment of Parkinson’s disease (PD).¹ The early symptoms and signs of Parkinson’s disease (resting tremor, bradykinesia and rigidity) are usually correctable by levodopa and dopamine agonists.² However, the oral bioavailability of levodopa is erratic and has a short half-life.³ This has been hypothesised as a cause of motor fluctuations and drug-induced dyskinesias. 

This has prompted treatments that circumvent the problems seen in oral therapy of levodopa. The development of levodopa/carbidopa intestinal gel infusion (Duodopa) seeks to provide continuous drug delivery of levodopa via a non-oral route.³ However, the quality of life (QoL) in patients is affected by both the motor and non-motor symptoms of Parkinson’s disease. This review will focus on the efficacy of Duodopa in treating the symptoms of Parkinson’s disease, as well as in improving the QoL of patients.

The authors conducted a PubMed search for Duodopa articles and also reviewed abstracts from meetings that included this topic. We focused on the efficacy of Duodopa in improving QoL of patients. Hence, studies that did not provide information on efficacy of Duodopa on QoL were not included. Publications that were not in English, did not study Duodopa, or did not investigate the effects of Duodopa on treatment of symptoms of Parkinson’s disease or improvements on patient QoL were not included. 

Subjects included were adults (aged ≥ 30 years) who had advanced Parkinson’s disease that met the UK Brain Bank criteria.⁴ Patients included had classical symptoms of advanced Parkinson’s disease including motor fluctuations and dyskinesias, which could not be satisfactorily controlled by oral levodopa therapy. Patients must have had a clinical response to levodopa previously to be included in the studies.

Duodopa is a cellulose gel suspension of levodopa and carbidopa. Dosage for each patient is calibrated on the basis of their previous oral dosage. Initial maintenance dose was calculated according to the levodopa equivalent daily dose (LEDD). Initial clinical response is tested by temporary Duodopa treatment through a naso-jejunal tube. Once a positive response is established, a percutaneous endoscopic gastrostomy (PEG) tube is inserted across the intestinal mucosa in the duodenum or jejunum. This tube is attached to a portable pump, which will provide continuous infusion of levodopa/carbidopa gel for immediate absorption by the intestinal mucosa.⁵

In all studies reviewed, patients were evaluated prior to PEG procedure. Parkinsonian motor features were assessed by means of the Unified Parkinson’s Disease Rating Scale (UPDRS).⁶ This scale allows the assessment of worsening or improvement of Parkinsonian motor features over time. Worsening of symptoms increases the score from the initial baseline recorded, while improvement in symptoms decreases the score. The UPDRS is further subdivided into four sections:  

• Part I on mentation, behaviour and mood
• Part II on ability to carry out activities of daily living (ADL)
• Part III on motor abilities 
• Part IV on complications of therapy. 

A study conducted by Fernandez et al⁷ showed that the mean ‘off’ time in patients who had completed treatment, or had ongoing treatment, was significantly reduced. ‘Off’ time in patients is during times of a state of decreased mobility. Mean (standard deviation (SD)) reduction of ‘off’ time at week 12 was 3.9 (3.2) hours/day, which further increased to 4.6 (2.8) hours/day. The mean ‘on’ time, where the medication is working, and the parkinsonian symptoms are controlled, also increased by a mean (SD) of 4.6 (3.5) hours/day at week 12, and 5.3 (2.7) hours/day at week 54. Substantial improvements were also noted in the UPDRS total and subscale scores.

In a multicentre study comprising centres in the UK, Germany and Italy conducted by Honig et al,⁸ patients reported significant improvement for the UPDRS-III motor and UPDRS-IV complications after six months of treatment. Specific items for dyskinesia (32 to 35) in UPDRS-III also showed significant improvement between baseline and follow-up. 

In the studies reviewed with data on quality of life, QoL in patients was evaluated by means of the UPDRS, as well as the Parkinson Disease Questionnaire (PDQ-39)⁹ prior to administration of Duodopa and also after treatment. Parts I and II of the UPDRS are pertinent with regards to their impact on a patient’s QoL, and improvements in their subscores and overall UPDRS score could be indicative of QoL. The PDQ-39 is an adequate tool in determining the effect PD has on the QoL, as well as the overall QoL in the patient. Subsections of PDQ-39 include emotional wellbeing (EMO), stigma (STI), cognition (COG), communication (COM) and bodily discomfort (BOD), which would be highly relevant with respect to dignity and respect of the patient. 

A study conducted in the UK by Foltynie et al¹¹ showed that there was a mean significant improvement seen in the PDQ-39 summary index as well as the subscores of ‘mobility’, STI and COG. It also showed evidence of improvement in six individuals, while in the other five, QoL was unchanged. After three months of Duodopa therapy, significant reductions were seen in the subsections of EMO (16%), STI (51%), COG (38%), COM (35%) and BOD (28%). 

Similarly, another study conducted in Italy by Zibetti et al¹² after three years of Duodopa treatment showed significant improvements in QoL, with a 27% reduction of the PDQ-39 summary index. In patients who managed to complete three years of continuous therapy with Duodopa without development of significant cognitive decline, there was a mean reduction of 41% in the EMO subsection, 33% reduction in the STI subsection, and 28% reduction in the COG subsection. However, it should be noted that there is no significant mean reduction in the bodily discomfort section (baseline mean (SD) = 32.1 hours against three-year follow-up mean (SD) = 31.4 (17.1)).

Most adverse events recorded in studies were related to the surgical procedure or infusion devices, including tube dislocations, percutaneous gastrojejunostomy insertion complications, stoma insertion complications, pump malfunctions and peritonitis in relation to tube placement. Other adverse events included polyneuropathy. Foltyine et al¹¹ noted during their UK study that patients who discontinued treatment after three months were due to difficulties with the delivery tube. Of the remaining who continued treatment, half had recurrent minor problems with the delivery tube. One patient also experienced hypergranulation around the PEG site requiring topical steroid application. 

With respect to the Duodopa treatment itself, two patients developed increased impulsivity, while no patient reported symptoms of neuropathy. Zibetti et al also noted that adverse events related to the infusion devices were the most common complications, in particular with the dislocation of the intestinal tube. Device problems were a contributing reason for the discontinuation of infusion in four out of five patients over the course of three years of the study. There was one case of psychosis that required Duodopa dose reduction and neuroleptic therapy, and there were several cases of peristomal infections, which were all resolved with conservative medical therapy.

Significant increase in the ‘on’ time of effective control of symptoms, coupled with reductions in the ‘off’ times indicate that continuous levodopa infusion is effective, and shows that the short half-life of levodopa is correlated to the development of ‘on’/‘off’ fluctuations that would reduce a patient’s QoL. Continuous levodopa infusion leads to a steady delivery of levodopa to the brain, and circumvents the short half-life of levodopa. 

However, these benefits must be weighed against the adverse effects of having to manage a portable pump daily, and the possible side-effects of neuropathy and device-related infections. While patients are better able to lead independent lives, frequent visits to the gastrointestinal team and the Parkinson’s disease team are required to ensure correct placement of the delivery tube, to ensure no infection has developed, and to titrate levodopa doses accordingly.

It should be noted that the need for a multidisciplinary team to monitor patients’ administration of Duodopa, and also that the treatment cost is more expensive than that of conventional oral levodopa therapy. However, in the long run, it could be more cost efficient if other factors were taken into account, such as hospital visits and repeated hospital admissions due to poor control of Parkinson’s disease, as well as community care savings resulting from increased independence of patients.

With better control of the Parkinsonian motor symptoms, patients are able to resume normal activities of daily living and regain a sense of independence. They are less affected by social stigma (due to better control of unwanted symptoms) and see improvements in their cognition, which all give rise to a better QoL. 

This improvement in QoL indicates that Duodopa has a more positive effect compared to conventional therapy. However, improvements are not seen in all aspects of the PDQ-39 subsections, with bodily discomfort showing little difference after treatment. 

This identifies a failure of levodopa to alleviate pain and discomfort in patients with Parkinson’s disease. However, the benefits gained from improvements in the QoL are significant, especially in patients with advanced Parkinson’s disease or who have been on long-term PD treatment.

Finally, the accuracy of PDQ-39 in the measurement of a PD patient’s QoL should be taken into consideration. Major aspects of a patient’s QoL such as patient’s long-term expectations with regards to Parkinson’s disease and long-term prognosis were not taken into account in the questionnaire. We were unable to assess the intrinsic effects on improvements in QoL due to shifts in patients’ expectations (which would likely improve due to better control of symptoms), nor the effect of Duodopa treatment on long-term prognosis of patients. 

Patient understanding that Duodopa is merely a symptomatic treatment would allow better management of patients’ expectations, but may result in a reduction in QoL due to the inevitable degeneration of patients’ conditions (not a cure). Hopefully research and development of a new drug that can both address the neurodegeneration and the symptoms associated with the degeneration would be useful, not only to achieve a cure for Parkinson’s disease, but which can return a patient’s QoL to pre-PD levels.

In conclusion, all studies have reported that Duodopa is clinically effective in relieving the symptoms of advanced Parkinson’s disease and improving patient’s QoL. There were persistent reductions in motor fluctuations and dyskinesias, as well as improvements of health-related QoL despite the burden of device-related complications. Most adverse effects were related to the administration of the drug rather than drug-induced, and it is hopeful that a less invasive mode of delivery could allow for better control of the symptoms of Parkinson’s disease.

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