The clinical spectrum of levodopa-induced motor complications

Abstract

After more than 40 years of clinical use, levodopa (LD) still remains the gold standard for symptomatic efficacy in Parkinson's disease (PD). However, long-term treatment with LD is often complicated by the development of various types of motor response oscillations as well as drug-induced dyskinesias. These treatment-related motor complications evolve in approximately one-third of patients after only 2 years of LD exposure and, once established, they are difficult to treat and significantly contribute to overall disability and disease burden. Although first described soon after the introduction of LD, the pathophysiology of motor complications is still not completely understood. In fact, it is most likely that non-physiological pulsatile stimulation of dopamine receptors, which is followed by various downstream alterations, plays a key role in the development of LD-induced motor response oscillations and dyskinesias. This review outlines the various types of motor complications and will also address underlying mechanisms, treatment options, as well as impact on clinical disability and quality of life (QoL).

Medication improves balance and complex gait performance in Parkinson disease

“…Motor symptoms of PD are most commonly treated pharmacologically with levodopa, a dopamine precursor. After prolonged levodopa treatment, motor response fluctuations often develop, resulting in sub-optimal medication benefits during portions of the medication cycle [2]. …”

Actively Transported Levodopa Prodrug XP21279

“…3,24 Attaining more consistent peripheral LD concentration is currently an unmet need for many patients with advanced PD. 5,25 The smaller percentage increase from predose tapping speed for XP21279 may be explained by a practice effect, as the test was always administered on CD-LD before XP21279.Furthermore, these BPRS data followed a similar time course and were generally consistent with the ON/OFF diary data, suggesting that the decrease in OFF time and increase in ON time without troublesome dyskinesia also correlate with the more consistent LD concentrations seen with XP21279 treatment. XP21279 when given with CD resulted in more sustained LD levels and, correspondingly, a better motor response than oral CD-LD.…”

Dopaminergic-induced dyskinesia assessment based on a single belt-worn accelerometer

“…Peak-dose dyskinesias are the most common and frequent type of dopaminergic-induced dyskinesias [9]. Consequently, they are the most interesting type, from a clinical point of view, in order to assess the adverse effects of specific medications [10]. [16,17].…”