Should there be less emphasis on levodopa‐induced dyskinesia in Parkinson's disease?

Abstract

Soon after the introduction of levodopa in to the treatment of Parkinson's disease (PD), 1 marked involuntary movements or dyskinesia were identified as a common serious and potentially disabling side effect of treatment. 2 The drug developed a negative reputation for the high incidence of dyskinesia-although much of this was because of the high dosage used and the introduction of treatment in patients with advanced, but previously untreated, disease. 3 Later studies reported that early use of L-dopa resulted in a high prevalence of involuntary movements of up to 36% within 5 years and up to 88% within 10 years. 4,5 These reports and the clinical experience of early initiation of L-dopa therapy led to the widespread view that dyskinesia was an almost inevitable consequence of the use of L-dopa. Not surprisingly, the medical community and the patient population took fright and the early initiation of L-dopa therapy diminished. Avoiding L-dopa treatment until necessary became a strategy for treating the younger patient population and eventually led to the early use of dopamine agonist drugs that appeared to result in a lower incidence of dyskinesia. 3 However, more recently, L-dopa has made a return to frontline treatment using more careful treatment paradigms and using lower daily doses that seem to lessen the risk of dyskinesia induction. The PDMED study has also consolidated the role of initiating treatment of PD with L-dopa, and the current view is that there is little evidence to justify withholding the drug in early disease. 6 Nevertheless, recent reports would, at first glance, seem to suggest that dyskinesia has not gone away as a problem of clinical significance. In 2012, Manson and colleagues reviewed the incidence of dyskinesia in PD and concluded that 40% to 50% of patients develop dyskinesia within 5 years of initiation of treatment and that this increases to 50% to 75% after 10 years. 7 Also, Ahlskog and Muenter, in their 2001 review, showed that the prevalence of dyskinesia increases from a nil dyskinesia state in recently diagnosed patients to 60.7% to 95.5% in patients with a disease duration of 9 to 15 years after L-dopa treatment of variable dose schedules. 5 The data is in overall agreement with another review by Tran and colleagues, 8 which also pointed out that the prevalence of dyskinesia depended on the age of onset of PD, disease duration, and severity and duration of L-dopa therapy-as might be expected from past publications. A further pointer toward a high dyskinesia rate is also evident in the CALM-PD trial, where 222 patients were randomised to receive either pramipexole or L-dopa, and it was shown that 6 years after initiation of treatment, prevalence of dyskinesia was high, at 68%, for L-dopatreated patients and 50% for those on pramipexole. Disabling and painful dyskinesia, however, were almost nonexistent in both groups (2.8% and 3.5% reported disabling dyskinesia and 5.6% and 3.5% reported painful dyskinesia, respectively). 17 In a community-based study of 124 patients, Schrag an...

The Movement Disorder Society Nonmotor Rating Scale: Initial Validation Study

“…This new scale complements the MDS‐UPDRS for use in epidemiological and clinical trials, allowing users and policy makers to obtain an in‐depth assessment of the effect of the disease and the impact of investigational agents. This is especially relevant as recent views suggest that motor complications in PD may be less prominent than in the past, whereas evidence for effective treatments of many NMSs in PD is still quite limited . In addition, we hope that the MDS‐NMS will help policy makers decide on the impact of a drug on value‐based health care, as well as help in creating national registries using postmarketing surveillance.…”

Dyskinesia Matters

“…Over the years, the health‐related burden of dyskinesia has been discussed in a number of publications, sometimes leading to discordant conclusions. The latest addition to this literature is the viewpoint article by Chaudhuri and colleagues recently published in Movement Disorders . Although the authors acknowledge that levodopa–induced dyskinesia (LID) still occurs to a high degree in PD, the main thrust of the article is that troublesome involuntary movements are not so common as they used to be and therefore dyskinesia “should not be given much emphasis as a matter of clinical significance or priority for research.”…”

“…This perception is supported by a debate that has recently arisen on the social media. Several people with PD have expressed concerns about the viewpoint by Chaudhuri and colleagues via the online forum Parkinson Research Interest Group, which is a patient‐driven discussion group aiming to promote a better understanding of the disease, foster informed communication, and motivate the PD community to be more involved in research. As the group's founder Martin Taylor puts it: “For those of us diagnosed today, the prospect of dyskinesia is either a bothersome reality or a deep concern for the future.…”

“…). Taken together, the ongoing discussions among people with PD contradict the authors’ contention that levodopaphobia is a rare phenomenon and that dyskinesia “does not worry the patients affected.”…”

“…We borrow 6 passages from the article by Chaudhuri and colleagues, which will serve as starting points for our considerations.

(1) “ Antidyskinesia management in PD (oral therapies, infusion therapies, DBS, and radioablation) have all focused on dyskinesia reduction (usually troublesome dyskinesia) as one of the key aims of the therapy along with improvement of off‐time in PD. However, a large body of clinical trials data point otherwise, and suggest that cautious use of levodopa therapy in low‐dose regimes or early use of longer‐acting therapies may substantially reduce the risk of troublesome dyskinesia in PD.”

…”