Limitations of current Parkinson's disease therapy

Abstract

Levodopa and other dopaminergic medications drastically improve the motor symptoms and quality of life of patients with Parkinson's disease in the early stages of the disease. However, once the "honeymoon" period has waned, usually after a few years of dopaminergic therapy, patients become progressively more disabled despite an ever more complex combination of available antiparkinsonian treatments. Sooner or later, they suffer from "dopa-resistant" motor symptoms (speech impairment, abnormal posture, gait and balance problems), "dopa-resistant" nonmotor signs (autonomic dysfunction, mood and cognitive impairment, sleep problems, pain) and/or drug-related side effects (especially psychosis, motor fluctuations, and dyskinesias). Therefore, the current antiparkinsonian therapy cannot be considered as ideal with regard to both efficacy and safety.

Adherence to antiparkinsonian medication: An in-depth qualitative study

“…These omissions are significant given the complexity of PD and its control, especially as many people with early-onset PD live at home and have face-to-face consultations with specialist practitioners only a few times a year. Problems are compounded because PD gradually impairs manual dexterity, vision and memory (Rascol et al 2003), all factors that interfere with ability to take drugs.…”

“…When the drug is working the patient is said to be "on.. The reverse condition (being "off..) reduces normal function and is particularly upsetting if it occurs in public (Rascol et al 2003). Timing is crucial to achieve maximum effectiveness under physically or mentally demanding circumstances (Chaudhuri et al 2007) and to reduce the obvious and stigmatising signs of parkinsonism (Chaudhuri et al 2007).…”

Estimating the value of novel interventions for Parkinson's disease: An early decision-making model with application to dopamine cell replacement

“…Data on survival probabilities were obtained from Swedish life tables [12]. Most studies indicate a somewhat increased mortality in PD compared to the general population [2]. To account for this, we used data from a study by…”

“…Available therapies offer major symptomatic relief during the initial stages of Parkinson's disease (PD), and approaches such as deep brain stimulation and continuous drug delivery systems can offer relief from disabling complications during later stages [1,2]. None of the therapeutic options clinically available for PD today has unequivocally been shown to modify the underlying disease process.…”

“…In order to gain acceptance, they will thus need to offer long-term gains beyond those offered by currently available therapies, not only in terms of efficacy and effectiveness but also regarding the disease-related societal burden [2]. It is currently unknown if or to what extent this can be reasonably expected to be achieved with novel candidate interventions for PD.…”