Question: What is the "wearing-off" phenomenon in levodopa-treated patients with Parkinson's Disease?

Context:
It is unlike the "wearing-off" phenomenon that occurs when dopaminergic drug levels decline and responds to dopaminergic rescue drugs. 
Unfortunately, chronic use of traditional levodopa/dopa decarboxylase inhibitor formulations is associated with the development of complications, such as wearing-off and dyskinesia.
One of the first complications observed with levodopa therapy is wearing-off, which can emerge within 1-3 years of initiation of levodopa treatment. Wearing-off is characterized by the predictable emergence of motor and nonmotor PD symptoms before the next scheduled dose of medication. Despite effective treatment options to tackle wearing-off, it remains underrecognized and under treated. 
Shortness of breath, a 'wearing-off' symptom in Parkinson's disease.
Although levodopa is considered the gold standard for Parkinson's disease therapy, prolonged use of this drug can result in motor complications such as a 'wearing-off' phenomenon. This outcome is seen in a significant number of patients with Parkinson's disease taking levodopa and, in some cases, is observed only a few hours after intake of the last dose of levodopa. Patients experiencing the wearing-off period may present with sensory, autonomic, psychiatric and motor fluctuations. Although infrequent, shortness of breath is an important non-motor wearing-off symptom experienced by patients with Parkinson's disease.
We report here on a patient with Parkinson's disease who was taking levodopa and developed both shortness of breath and hyperventilation during wearing-off periods.
His shortness of breath was determined to be a wearing-off phenomenon and his condition improved with the addition of a catechol-O-methyltransferase inhibitor (entacapone).
The wearing-off phenomenon in patients with Parkinson's disease (PD) is a complication of prolonged levodopa usage. During this phenomenon, motor symptoms such as rigidity and freezing re-emerge. This is often accompanied by non-motor symptoms, including anxiety, the so-called wearing-off related anxiety (WRA). 
Patients with wearing-off tended to receive higher L-dopa dosage and endure longer duration of L-dopa treatment. 
The wearing-off phenomenon frequently complicates levodopa therapy of Parkinson's disease (PD).
The effects of tolcapone, a catechol-O-methyltransferase inhibitor, on the bioavailability and efficacy of levodopa were evaluated in 12 patients with Parkinson's disease (PD), 8 of whom showed signs of daily motor fluctuations (wearing-off phenomenon).
Although infrequent, shortness of breath is an important non-motor wearing-off symptom experienced by patients with Parkinson's disease.
Although levodopa is considered the gold standard for Parkinson's disease therapy, prolonged use of this drug can result in motor complications such as a 'wearing-off' phenomenon.
More than 50% of patients with Parkinsons disease develop motor response fluctuations (the wearing off" phenomenon) after more than five years of levodopa therapy
More than 50% of patients with Parkinsons disease develop motor response fluctuations (the "wearing off" phenomenon) after more than five years of levodopa therapy
The wearing-off phenomenon in patients with Parkinsons disease (PD) is a complication of prolonged levodopa usage
Short-term effect of a single levodopa dose on micturition disturbance in Parkinsons disease patients with the wearing-off phenomenon
To evaluate the effectiveness of entacapone in the management of levodopa wearing-off in Parkinsons disease (PD) in a naturalistic, real-life setting.This prospective, open-label, observational study included patients with idiopathic PD. Patients were eligible for inclusion if they had been taking 3-5 doses of levodopa per day for ≥2 months and had shown signs of levodopa wearing-off for ≥1 month
The duration of clinical control of motor symptoms of Parkinson disease (PD) treated with levodopa/carbidopa preparations eventually starts to shorten, a phenomenon known as end-of-dose "wearing off." The involvement of core nonmotor symptoms of "wearing off" (depressed mood, pain/aching, anxiety, and cloudy/slowed thinking) is not well understood.
Efficacy and tolerability of entacapone in patients with Parkinsons disease treated with levodopa plus a dopamine agonist and experiencing wearing-off motor fluctuations
The efficacy and tolerability of entacapone was investigated in a randomized, double-blind, placebo-controlled, 3-month study of 162 patients with Parkinsons disease (PD) treated with levodopa and a dopamine agonist and experiencing wearing-off motor fluctuations
Efficacy and safety of entacapone in levodopa/carbidopa versus levodopa/benserazide treated Parkinsons disease patients with wearing-off
We conclude that tolcapone as an adjunct offers promise for the relief of the "wearing-off " phenomenon in levodopa-treated parkinsonian patients.
We conclude that tolcapone as an adjunct offers promise for the relief of the "wearing-off" phenomenon in levodopa-treated parkinsonian patients.
Our data also support the involvement of postsynaptic dopamine receptor mechanisms in the wearing-off phenomenon seen in levodopa-treated parkinsonian patients.
Short-term effect of a single levodopa dose on micturition disturbance in Parkinson's disease patients with the wearing-off phenomenon.
It is unlike the "wearing-off" phenomenon that occurs when dopaminergic drug levels decline and responds to dopaminergic rescue drugs. 
More than 50% of patients with Parkinson's disease develop motor response fluctuations (the 'wearing off" phenomenon) after more than five years of levodopa therapy.
The primary objective of this study was to assess the effect of tolcapone on levodopa dosage in parkinsonian patients whose "wearing-off" phenomenon has been controlled with more frequent levodopa dosage.
More than 50% of patients with Parkinson's disease develop motor response fluctuations (the "wearing off" phenomenon) after more than five years of levodopa therapy.
To evaluate the role of the practicing pharmacist in the identification and current treatment of the levodopa wearing-off phenomenon experienced by patients with Parkinson's disease (PD) who are receiving chronic levodopa therapy.Literature retrieval was accessed through MEDLINE (1967-June 2007) using the terms levodopa, wearing-off, and Parkinson's disease.
This study investigated the effects of OPC in comparison with placebo on levodopa pharmacokinetics, tolerability and safety, COMT activity and motor response to levodopa in Parkinson's disease (PD) patients with motor fluctuations.This was a randomized, multicentre, double-blind and placebo-controlled study in four parallel groups of PD patients treated with standard-release 100/25 mg levodopa/carbidopa or levodopa/benserazide and with motor fluctuations (wearing-OFF phenomenon).
Patients experiencing the wearing-off period may present with sensory, autonomic, psychiatric and motor fluctuations. Although infrequent, shortness of breath is an important non-motor wearing-off symptom experienced by patients with Parkinson's disease.
This outcome is seen in a significant number of patients with Parkinson's disease taking levodopa and, in some cases, is observed only a few hours after intake of the last dose of levodopa. Patients experiencing the wearing-off period may present with sensory, autonomic, psychiatric and motor fluctuations. Although infrequent, shortness of breath is an important non-motor wearing-off symptom experienced by patients with Parkinson's disease.
Although levodopa is considered the gold standard for Parkinson's disease therapy, prolonged use of this drug can result in motor complications such as a 'wearing-off' phenomenon. This outcome is seen in a significant number of patients with Parkinson's disease taking levodopa and, in some cases, is observed only a few hours after intake of the last dose of levodopa. Patients experiencing the wearing-off period may present with sensory, autonomic, psychiatric and motor fluctuations.
It is suggested that tolcapone may be useful drug adjunct to levodopa in treating patients with PD with wearing-off phenomena.
It is suggested that tolcapone may be useful drug adjunct to levodopa in treating patients with PD with wearing-off phenomena..
Levodopa-treated Parkinson's disease is often complicated by the occurrence of motor fluctuations, which can be predictable ('wearing-off') or unpredictable ('on-off').
She was treated with 400 mg/day of levodopa-carbidopa, which improved her symptoms, however, she developed wearing off phenomenon 3 years after the initiation of levodopa treatment.
[Benefit of L-DOPA-without-DCI (decarboxylase inhibitor) therapy on wearing-off phenomenon in advanced stages of Parkinson's disease patients].
To evaluate the role of the practicing pharmacist in the identification and current treatment of the levodopa wearing-off phenomenon experienced by patients with Parkinson's disease (PD) who are receiving chronic levodopa therapy.
However, once the decision to initiate levodopa therapy has been made, studies generally support the use of entacapone as an adjunct to levodopa in patients with Parkinson's disease and the 'wearing off' phenomenon..
These results suggest that wearing-off phenomenon may arise as a consequence of the degeneration of dopamine terminals due to natural disease progression with a resultant inability to buffer variations in levodopa availability; on-off phenomenon, may reflect additional postsynaptic dopamine receptor dysregulation, possibly in response to the resultant, nonphysiologic fluctuations in synaptic dopamine..
Conversion from oral to intravenous levodopa treatment immediately stabilized plasma levodopa levels in both the wearing-off and on-off groups; motor variability also decreased, especially in those with wearing-off phenomenon.

Answer: Chronic administration of traditional levodopa/dopa decarboxylase inhibitor formulations to Paskinson's Disease patients is associated with the development of complications, such as wearing-off phenomenon. Wearing-off phenomenon is characterized by the predictable emergence of motor symptoms (e.g. rigidity and freezing) and nonmotor PD symptoms (e.g. anxiety and shortness of breath), before the next scheduled dose of medication.