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Table 1 Recommendation for the management of the wearing-off phenomenon

From: The recommendations of Chinese Parkinson’s disease and movement disorder society consensus on therapeutic management of Parkinson’s disease

Increase the frequency of drug taking with the same daily dose, or appropriately increase the total daily dose.

Switch immediate-release levodopa to controlled-release levodopa or extended-release levodopa to prolong the action of levodopa. They are more appropriate for the wearing-off phenomenon in early-stage PD. The dosage of controlled-release levodopa should be increased by 20 − 30 % after switching from immediate-release levodopa, because of its low bioavailability. The US guidelines reported that this could not decrease the off stage (Level C evidence) [44], while the UK NICE guidelines recommended this application in advanced-stage PD, but not as the first choice (Level B evidence) [92].

Add long half-life dopamine agonists, including pramipexole and ropinirole (Level B evidence), cabergoline and apomorphine (Level C evidence) [44]; however, bromocriptine could not shorten the off stage (Level C evidence) [44]. Other dopamine agonists could be used to replace the currently used dopamine agonists that lose their efficacy.

Add COMT inhibitors to generate continuous dopaminergic stimulation to the striatum, including entacapone (Level A evidence) and tolcapone (Level B evidence) [44].

Add MAO-B inhibitors, such as rasagiline (Level A evidence) and selegiline (Level C evidence) [44].

Minimize the impact of protein diet on the uptake and blood − brain barrier crossing of levodopa. Drugs should be taken 1 h before or 1.5 h after meals.

Surgical intervention, such as DBS of the subthalamic nucleus (STN) (Level C evidence), is helpful.