Parkinson ‘s disease (PD), also known as tremor palsy, is a common neurodegenerative disease of the middle-aged and elderly. As the population ages, its prevalence is increasing year by year, negatively impacting families and society alike. PD has been known for 192 years since it was first described by James Parkinson in 1817. In the last 30 years or so, especially in the last decade or so, there has been great progress in both the understanding of the pathogenesis of PD and the exploration of treatments. The Neurology Branch of the Chinese Medical Association proposed the treatment of primary PD in 1998, and the Parkinson’s Disease and Movement Disorders Group formulated the first Chinese PD treatment guidelines in 2006, which played an important role in standardizing the treatment of PD in China. In the past 30 years, there have been more advances and new understanding in this treatment field abroad. In order to better adapt to its development and to better guide clinical practice, we make necessary modifications and additions to the PD treatment guidelines formulated 3 years ago. 1. Treatment principles (1) Comprehensive treatment The motor symptoms and non-motor symptoms of PD should be treated in a comprehensive manner, including pharmacotherapy, surgery, rehabilitation, psychotherapy and nursing care. Drug therapy, as the first choice, is the main treatment tool in the whole treatment process, while surgery is an effective complementary tool to drug therapy. The currently applied treatments, whether medication or surgery, can only improve the symptoms and cannot stop the development of the disease, let alone cure it. Therefore, treatment should not only take into account the immediate future but not the future. (2) Medication principles The goal is to achieve effective improvement of symptoms and quality of life, and to insist on “dose titration” and “satisfactory effect with minimum dose”. The treatment should follow the general principles and also emphasize the individualized characteristics, and the selection of medication for different patients should not only consider the characteristics of the disease, but also consider the patient’s age, employment status, affordability and other factors. The side effects and complications of drugs should be avoided or reduced as much as possible, and the drug treatment, especially the use of levodopa, should not be stopped suddenly to avoid the occurrence of levodopa withdrawal malignant syndrome. 2. Drug therapy (1) Protective therapy The purpose of protective therapy is to delay the development of the disease and improve the patient’s symptoms. In principle, once PD is diagnosed, it should be treated as early as possible. At present, the main drugs used as protective therapy in clinical practice are monoamine oxidase-B (MAOB) inhibitors. It has been reported that treatment with selagiline + vitamin E (deprenyl andtocopherol antioxidative therapy of Parkinsonism, DATATOP) can delay disease progression (about 9 months), delay the use of levodopa and resagiline may also have the effect of delaying disease progression but further confirmation. Several clinical trials have suggested that dopamine receptors (DR) agonists may have a neuroprotective effect; clinical trials of high-dose coenzyme Q10 have also been suggested to have a possible neuroprotective effect, but further confirmation is needed. (2) Symptomatic treatment Early PD treatment (Hoehn-Yahr grade 1-II) When to start medication If the disease does not affect the patient’s life and work ability in the early stage of the disease, the patient should be encouraged to adhere to work, participate in social activities and medical physical therapy, and symptomatic treatment medication can be suspended; if the disease affects the patient’s daily life and work ability, symptomatic treatment should be started. Preferred drug principles (1) Patients younger than 65 years old and not accompanied by mental retardation can choose ① non-ergot DR agonist; ② MAO-B inhibitor or add vitamin E; ③ amantadine, if tremor is obvious and the effect of other anti-PD drugs is not good, you can choose anticholinergic drugs; ④ compound levodopa + catechol-O-methyl transferase (COMT) inhibitor. transferase (COMT) inhibitor, i.e., Stalevo; ⑤ compound levodopa is usually added when ①, ② and ③ are not effective. The preferred drugs are not exactly in the above order, and different regimens should be chosen according to the patient’s condition. If the patient is in compliance with the treatment guidelines in the United States and Europe, ① is preferred, and ② or ④ is preferred; if the patient cannot afford the high price of the drug for financial reasons, ③ is preferred; if the patient needs to improve motor symptoms significantly due to special work or has cognitive impairment, ④ or ⑤ is preferred, or ①, ② or ③ can be applied in small doses, and ⑤ can be combined in small doses. (2) Patients older than 65 years of age or with diminished intelligence: compound levodopa is preferred, and DR agonist, MAO-B or COMT inhibitor can be added if necessary. Benzedrine has more side effects do not use if possible, especially in elderly male patients, unless there is severe tremor well significantly affect the patient’s ability to perform daily life. Therapeutic drugs (1) Anticholinergic drugs: The main ones are benzhexol, usage 1 to 2 mg, 3 times a day. Also available are kairomadrine, benztropine, scopolamine, and cyclopentanol. It is mainly used in patients with tremor, but not in patients without tremor, especially in elderly patients, and is prohibited in patients with narrow-angle glaucoma and prostatic hypertrophy. (2) Amantadine: Usage 50-100 mg, 2-3 times daily, the last dose should be taken before 4:00 pm. It has improved the effect of hypokinesia, tonicity and tremor, and may be helpful for patients with heterokinesia. Use with caution in patients with renal insufficiency, epilepsy, severe gastric ulcer, liver disease, and contraindicated in nursing mothers. (3) Compound levodopa (benserazide levodopa, carbidopa levodopa): Initial dose 62.5~125.0 mg, 2~3 times daily, gradually increase the dose according to the condition to the appropriate dose for maintenance treatment with satisfactory efficacy and no side effects, 1 h before or 1.5 hours after meal. Use with caution in patients with active gastrointestinal ulcers, narrow-angle glaucoma, psychiatric patients are prohibited. (4) DR agonists: Currently most of the non-ergot DR agonists are preferred. Drugs are especially used in young patients early in the course of the disease. Because these long half-life agents can avoid the striatal postsynaptic membrane DR “pulse” stimulation, thereby preventing or reducing the occurrence of motor complications. Agonists should be started at small doses and increased until satisfactory efficacy is achieved without side effects. There are two types of DR agonists: ergots, including oxytocin, pergolide, alpha-dihydroergotocryptine, ergometrine, and ergometrine; and non-ergot agonists, including pramipexole, ropinirole, vibradil, ropinirole, and apomorphine. and apomorphine. Ergot DR agonists can lead to cardiac valve lesions and pulmonary pleural fibrosis, and their use is now discouraged, while pergolide has been discontinued in China. No non-ergot DR agonists have been found to have this side effect. Currently, the non-ergot DR agonists available in China are: ①Vibedil Rescue Release Tablets: initial dose of 50 mg once daily, which can be changed to 25 mg twice daily for patients prone to side effects, and increased to 50 mg twice daily in the second week, with an effective dose of 150 mg/d divided into 3 oral doses, not exceeding 250 mg/d; ②Praxol: initial dose of 0.125 mg three times daily ( ②pramipexole: initial dose of 0.125 mg 3 times daily (1 to 2 times for individual patients prone to adverse reactions), increased by 0.125 mg 3 times a day every week, generally effective dose of 0.50-0.75 mg 3 times a day, maximum 4.5 mg/d. Domestic marketed ergot DR agonists: ①bromocriptine: 0.625 mg once daily, increased by 0.625 mg every 5 days, effective dose of 3.75-15 mg/d, divided into 3 doses. ②α-dihydroergotocryptine: 2.5 mg, twice daily, with an increase of 2.5 mg every 5 d. The effective dose is 30-50 mg/d, divided into 3 oral doses. The dose conversion between the above 4 drugs is: vibradil: pramipexole: oxytetracycline: α-dihydroergotocryptine = 100:1:10:60, which can be used as a reference. (5) MAO-B inhibitors: Currently, there are silegiline and soon to be resagiline in China. The usage of Silegiline is 2.5-5. 0 mg twice daily, should be taken in the morning and noon, do not use in the evening or night to avoid insomnia, or combined with vitamin E 2000 IU (DATATOP program); the usage of Resagiline is 1 mg once daily, taken in the morning. The absorption, action and safety of the new dosage form Zydis Slegiline are better than those of Slegiline standard tablets, and the usage is 1.25-2.50 mg/d. It is not yet available in China. It should be used with caution in patients with gastric ulcer, and is prohibited to be used in combination with selective serotonin reuptake inhibitor (SSRI). (6) COMT inhibitors: entocapone or tolcapone. Entocapone 100-200 mg per dose, same number of doses as co-levodopa, or less than co-levodopa if more co-levodopa is taken daily, Entocapone should be taken together with co-levodopa, and is not effective alone. Side effects include diarrhea, headache, excessive sweating, dry mouth, elevated aminotransferase, abdominal pain, and yellowing of the urine. Tolcapone has the potential to cause hepatic impairment and liver function must be monitored closely, especially during the first 3 months of dosing. Treatment with Stalevo (a combination of entocapon-levodopa-carbidopa) has the potential to prevent or delay the onset of motor complications if preferred in untreated early-stage patients. Patients who are treated with DR agonists, MAO-B inhibitors, or amantadine/anticholinergics in the early phase should be treated with levodopa in the middle phase, when the improvement of symptoms is no longer obvious. Patients who are treated with low-dose compound levodopa preferred in the early stage may not have significant symptom improvement in the middle stage, and then the dose should be increased or DR agonist MAO-B inhibitor, amantadine or COMT inhibitor should be added. Some patients in the mid-stage may also develop motor complications and/or non-motor symptoms, which are addressed in detail in the treatment of advanced PD. Treatment of advanced PD (Hoehn-Yahr N to V levels) The clinical manifestations of advanced PD are extremely complex, with factors involved in the progression of the disease itself as well as in drug side effects or complications. It is important to emphasize that because of the lack of treatment response to advanced PD, early treatment response is particularly important and clinicians should consider the long-term effects at the early stage of treatment. The treatment of patients with advanced PD should continue to aim at improving motor symptoms on the one hand, and dealing with some possible motor complications and non-motor symptoms on the other.