When Do Levodopa Motor Fluctuations First Appear in Parkinson’s Disease?

Abstract

Although levodopa provides therapeutic benefit over the entire course of Parkinson’s disease, most patients eventually notice a decline in the duration of benefit from each dose, a phenomenon termed ‘wearing-off’ or ‘end of dose’ deterioration. This is an important indicator that the patient is entering a more complex phase of the disease. Wearing-off has been classically associated with the later stages of Parkinson’s disease, but it is becoming apparent that patients with early disease, presenting as well controlled, may already be experiencing fluctuations in their response to levodopa. However, neither the pathophysiology nor the clinical relevance of the early emergence of wearing-off has been properly explored. We now review the preclinical and clinical evidence that suggests that even patients who are apparently still in the honeymoon phase of drug treatment may have early fluctuations in their motor response to dopaminergic therapy. It is important that early wearing-off is recognized as it has important consequences for the long-term outcome and for the medication regimens to be used.

Quality of Life in Parkinson’s Disease – Patient, Clinical and Research Perspectives

“…48,49 Estimates based on some studies indicate that up to 50 % of patients with PD will experience motor fluctuations within the first 2 years of treatments. 50 In addition, the Earlier versus Later Levodopa Therapy in Parkinson Disease (ELLDOPA) study showed that complications can occur within the first year. 51 A recent study designed to evaluate the presence of motor and non-motor fluctuations using a specific questionnaire, the 19- 53,54 Therefore, in the clinic, HRQoL assessments should be easy to use and complement traditional diagnostic evaluations used by physicians.…”

“…Wearing-off can appear early in the course of the disease but often is not recognised by patients and doctors. 50 Early morning symptoms, particularly akinesia, have been shown to be correlated with motor aspects of PD and have strongly negative effect on HRQoL as perceived by patients. 46,63,64 The impact of morning akinesia, nocturnal akinesia and biphasic dyskinesias can be effectively Table 2).…”

Algorithms for the treatment of motor problems in Parkinson's disease

“…With time, postural changes and especially gait‐related problems may often be troublesome 3. Dopaminergic treatment can alleviate motor symptoms for some time, but motor fluctuations may appear even at early stages of the disease 4. Therefore, most treatment strategies also aim at delaying the evolvement of motor fluctuations as long as possible.…”

Specificity and sensibility of 9-Itens Wearing-off Questionnaire in Brazilian Parkinson disease patient sample

“…Levodopa (LD) remains the most effective and widely prescribed drug in the symptomatic treatment of PD 1 . Currently it is acknowledged that up to 50% of patients have motor fluctuations after two years of the introduction of LD or another dopaminergic agonist (DA) 2,3 . The long-term use of levodopa leads to complications directly related to the duration of the treatment.…”

“…Wearing-off (WO) is one subtype of motor fluctuation and occurs over time, when the effectiveness of a dose of dopaminergic agonist tends to wear off earlier than before. For confirmation of this phenomenon, WO symptoms should improve after the intake of the next dose of antiparkinsonian drug (AD) 2 . The physiopathology of WO is controversial; it could be due to the decrease of the pre-synaptic dopamine receptors with consequent diminished storage capacity of dopamine in the striatum, or beyond post-synaptic mechanisms as the interruption of signal transduction for synthesis of proteins mediated by D1 and D2 receptors, or because of dopamine depletion due to neuronal loss.…”