Quality of Life in Advanced Parkinson’s Disease Patients Treated with Levodopa Infusion Therapy

Quality of Life in Advanced Parkinson’s Disease Patients Treated with Levodopa Infusion Therapy
Samanta Johan
European Neurological Review Volume 3 Issue 2 2008 Supplement
Published: November 2008
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Motor fluctuations are a common problem in the long-term management of Parkinson’s disease (PD). They result in disability and impaired quality of life. The relatively short serum half-life (~90 minutes) of oral levodopa/carbidopa and its inconsistent absorption in the intestines owing to delayed and erratic gastric emptying (a non-motor feature of PD) are thought to be important factors in the development of motor fluctuations. Continuous infusion of levodopa/carbidopa directly into the small intestine of PD patients reduces plasma levodopa variability by an order of magnitude over oral therapy, resulting in a marked reduction of motor fluctuations. Previously, the utility of long-term intraduodenal (ID) infusion was limited by the relatively large volumes of infusate required, as levodopa is poorly soluble in water/saline. The development of a micronised levodopa (20mg/ml) and carbidopa (5mg/ml) suspension in a methylcellulose gel (Duodopa) provides the high levodopa concentration and physical and chemical stability necessary for long-term enteral therapy. Clinical evidence indicates that a marked reduction of motor fluctuations and dyskinesias can be achieved and maintained by ID administration of this suspension. This article reviews the published data describing the effects of motor fluctuations on quality of life in PD and discusses the current and potential role of ID levodopa in meeting the needs of patients.

One of the elements in quality of life (QoL) in Parkinson's disease (PD) is keeping the patients in an on state. However, there is more to QoL than simply keeping patients on: a growing body of literature exists that examines the elements that most affect QoL in PD. One common conclusion was that the general health perceptions, health satisfaction and overall health-related QoL of PD patients are most closely correlated to psychosocial status (including educational, behavioural and psychological elements) as opposed to severity of physical symptoms.1,2 Depression and cognitive impairment are ecifically associated with poor QoL. This should not be taken to mean that motor function is unimportant in improving QoL, but rather that the relationship between motor function and QoL must be viewed in a wider context.

Levodopa-induced non-motor complications, which can include nausea, hallucinations, insomnia and fatigue, certainly have a significant impact on physical functioning, but emotional wellbeing is affected as well.3–5 Furthermore, motor fluctuations and dyskinesias may be embarrassing and interfere with activities of daily living (ADL), hence also reducing QoL.6 Motor state and mood may even fluctuate in unison, often with severe feelings of depression, anxiety and hopelessness emerging with every off episode, to be replaced by feelings of euphoria and even symptoms of mania in the dyskinetic state. Therefore, keeping patients 'on' and avoiding motor fluctuations are indeed important component sof QoL.

Assessing Quality of Life
There are a number of instruments available to assess QoL, although as yet none is ideal. Commonly used instruments include the Universal Parkinson's Disease Rating Scale (UPDRS), which is well known and understood: part I concerns mentation, part II concerns ADL and part IV covers therapeutic complications. There is also the PDQuestionnaire – 39 items (PDQ-39), which is sub-divided into physical, emotional and cognitive aspects of daily life. Other measures include recording on/off time, although on time itself can vary in quality: for xample, it would be poor quality on time if the patient also sufferedfrom dyskinesia.

Levodopa Oral Therapy
Levodopa is the most potent antiparkinson drug available, and generally is associated with only a few, well-tolerated side effects. After a 'honeymoon' period of excellent clinical response to levodopa herapy, which can last for three to five years, the duration of effect ofeach individual dose of levodopa slowly begins to shorten. The majority of patients treated long-term (for more than six years) with levodopa will eventually develop a fluctuating motor response to dosing. To begin with these fluctuations are small, but they become more complex and unpredictable over time.7

Keywords:
levodopa, Parkinson's disease (PD), depression

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