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Abstract
Most Parkinson’s disease patients will receive levodopa therapy, and of these, the majority will develop some levodopa-induced complications. For many patients, the first complication to develop is the decline in the duration of therapeutic benefit of each levodopa dose, a phenomenon commonly termed ‘wearing-off’. There is already extensive literature documenting the epidemiology and management of wearing-off in Parkinson’s disease patients of western descent. However, data derived from these studies might not always apply to patients of Asian descent due to genetic variations, differences in co-morbidities or non-availability of certain drugs. This review summarizes the current literature regarding the epidemiology of wearing-off in Asian (including Arab) patients and discusses the management issues in the context of drug availability in Asia.
Financial & competing interests disclosure
This study was supported by the Ratchadapiseksompoj Endowment Fund of Chulalongkorn University (RES560530136 & RES560530137-HR), and research unit grant of Chulalongkorn University. We thank Anita Chadha-Patel for her assistance with literature searching, referencing and editing in the development of this report. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Most Parkinson’s disease (PD) patients will receive levodopa therapy, and of these, the majority will develop some levodopa-induced complications. Wearing-off is often the first complication to develop and, as such, can be considered a signal that the patient is entering a more complex stage of the disease.
There is already an extensive literature documenting the epidemiology and management of wearing-off in PD patients of western descent. However, data derived from these studies might not always apply to patients of Asian descent due to genetic variations, differences in co-morbidities or non-availability of certain drugs.
Although the cross-sectional studies published have confirmed that wearing-off fluctuations are common in the Asian population, relatively little is known about the time course of developing this problem and further studies are warranted in the Asian populations.
Non-motor fluctuations are a common problem in Asian PD patients, and it is important that physicians routinely ask their patients about all the possible signs and symptoms of wearing-off.
Use of the wearing-off questionnaire-9 may facilitate earlier detection of wearing-off and allow therapy optimization to be implemented. However, in order to differentiate wearing-off from sub-optimal titration, it is also important to ascertain that the patient is experiencing a change in his/her response to levodopa (i.e., that the patient previously had a good response to his/her levodopa regimen).
Other limitations of screening tools include the focus on day-time symptoms, when many Asian patients also suffer from nocturnal fluctuations.
There are a number of medications available (including catechol-O-methyltransferase inhibitors, monoamine oxidase type B inhibitors, dopamine agonists) for the management of wearing-off. Although the level of evidence from randomized controlled trials in Asian populations is variable for each drug, routine clinical experience supports their general efficacy and safety.
Options for advanced fluctuations (when oral therapies are not sufficient) include apomorphine, levodopa infusion and deep brain stimulation. However, there are little or no studies of apomorphine and levodopa infusion in the Asian population, and the Asian availability of these treatments is variable.
Most Asian treatment guidelines follow the western guidelines, but there are some important differences. For example, patients in Japan can also receive adjunct treatment with the antiepileptic zonisamide and the adenosine A2A antagonist istradefylline, which are not generally available in other countries. Likewise, the initial starting dose of entacapone in Japan is 100 mg (and not 200 mg as in western guidelines).
Although the current evidence is that the clinical features of PD in Arabs are not significantly different from other populations, very little is currently known about the development of wearing-off in the Arab population. There are currently no standard treatment algorithms among Arab countries regarding the diagnosis and management of wearing-off. If established, the Arab guidelines will have to be very specific, given the unique ancestry and co-morbidities of this underserved population.