Background
Contents
Principles of therapy
Comprehensive treatment
Principles of medication
Pharmaceutical therapies
Treatment of early-stage PD
Treatment of advanced-stage PD
Management of motor complications
Management of symptom fluctuations
① Increase the frequency of drug taking with the same daily dose, or appropriately increase the total daily dose. ② 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]. ③ 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. ④ Add COMT inhibitors to generate continuous dopaminergic stimulation to the striatum, including entacapone (Level A evidence) and tolcapone (Level B evidence) [44]. ⑤ Add MAO-B inhibitors, such as rasagiline (Level A evidence) and selegiline (Level C evidence) [44]. ⑥ 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. ⑦ Surgical intervention, such as DBS of the subthalamic nucleus (STN) (Level C evidence), is helpful. |
Management of dyskinesias
① Reduce the single dose of levodopa/benseraside or levodopa/carbidopa per time; or appropriately add dopamine agonists or COMT inhibitors if the motor symptoms deteriorate after the dose of levodopa is reduced. ② Add amantadine (Level C evidence) [44]. ③ Add atypical neuroleptics, such as clozapine, but start with an initial low dosage and then increase gradually, and closely monitor granulocytes. ④ Replace controlled-release levodopa with immediate-release levodopa to avoid the cumulative effects of controlled-release levodopa, which can aggravate dyskinesia. |
① Replace controlled-release levodopa with immediate-release levodopa, preferably with madopar dispersible, which can be used to manage the beginning-of-dose dyskinesia. ② Add long half-life dopamine agonists or COMT inhibitors, which can extend the half-life of plasma levodopa, thus increasing the area under the curve, and relieving the end-of-dose dyskinesia. This may also benefit the beginning-of-dose dyskinesia. |