(A) Treatment options 1. Depression: (1) Non-pharmacological treatment: The literature reports that transcranial magnetic stimulation (rTMS) can improve depressive symptoms in patients with Parkinson’s disease with comparable effects to fluoxetine (2 Level III evidence). There is no specific recommendation because one study lacked a placebo control and the other study had a small number of cases and no conclusive evidence to support or deny the effectiveness of rTMS for depression in Parkinson’s disease. (2) Pharmacotherapy: 1 multicenter, large sample, double-blind, placebo-controlled clinical study of 323 patients with depression in Parkinson’s disease applying the dopamine agonist pramipexole observed the efficacy of the drug and found that it reduced depression scores in patients with Parkinson’s disease (level I evidence). Another study showed that pramipexole significantly reduced depressive symptoms in patients with Parkinson’s disease compared with pergolide (level 1lI evidence), but the study was deficient in that the two groups differed in depression severity at baseline level. The monoamine oxidase I B inhibitor slaquiline (propargyl amphetamine) is used as an antidepressant drug for depression, but there are no evidence-based medical reports from abroad on the use of slaquiline for depression in Parkinson’s disease. In a multicenter, randomized, controlled, open study in China, 143 patients with Parkinson’s disease were treated with slegiline and vitamin E or vitamin E alone for 12 weeks, and the results suggested that slegiline had significant efficacy on tremor, hypermobility and tonicity, the main symptoms of Parkinson’s disease, and concomitant depressive symptoms (Class III evidence). Silegiline may improve depressive symptoms in Parkinson’s disease and can be used in moderation in patients without concomitant psychotic symptoms, and patients should be monitored for psychotic symptoms. Combination with selective 5-hydroxytryptamine reuptake inhibitor (SSRI) class antidepressants may induce 5-hydroxytryptamine syndrome, so it should not be combined with SSRI class drugs. A double-blind, placebo-controlled study of 48 depressed patients with Parkinson’s disease found that the tricyclic antidepressants desipramine and citalopram both improved the symptoms of depression associated with Parkinson’s disease, with the effect starting to be apparent in the desipramine group after 14 d and not in the citalopram group after 30 d. Both desipramine and citalopram improved the oral column of depressive symptoms associated with Parkinson’s disease (Class II evidence). One single-blind study suggested that both amitriptyline and sertraline could improve Parkinson’s disease depressive symptoms III1 (level III evidence); however, there was no clear improvement in the 39-item score of the Parkinson’s Disease Quality of Life Questionnaire in the amitriptyline group, and sertraline could improve the 39-item score of the Parkinson’s Disease Quality of Life Questionnaire in patients with Parkinson’s disease; this study lacked placebo control, and the evidence for the effectiveness of amitriptyline and A randomized, double-blind, placebo-controlled study found that the tricyclic antidepressant nortriptyline improved symptoms of depression associated with Parkinson’s disease (Level II evidence), suggesting that nortriptyline may also be used in the treatment of depression associated with Parkinson’s disease. SSRIs are currently the most commonly used drugs in patients with Parkinson’s disease with depression, and their antidepressant effect is less than that of tricyclic antidepressants, but they have fewer adverse effects, are well tolerated, and are more commonly used in clinical practice. A recent double-blind, randomized, placebo-controlled study investigating the efficacy of paroxetine and venlafaxine extended-release capsules on depression in Parkinson’s disease collected 115 patients with depression in Parkinson’s disease and treated for 12 weeks. The results showed that both paroxetine and venlafaxine extended-release capsules significantly improved symptoms of depression in Parkinson’s disease and did not exacerbate motor symptoms in Parkinson’s disease (Level I evidence). Another double-blind, placebo-controlled study comparing the efficacy of paroxetine controlled release, norethindrone and placebo in patients with depressed Parkinson’s disease suggested that paroxetine controlled release did not significantly improve depressive symptoms in patients with Parkinson’s disease. Other studies also suggest that fluoxetine, sertraline, and citalopram all lack sufficient evidence for their efficacy in depression in Parkinson’s disease. Atomoxetine is a novel norepinephrine reuptake inhibitor (NRI).1 A double-blind, placebo-controlled study suggested a tendency for the atomoxetine group to improve depression associated with Parkinson’s disease and to improve overall cognition and reduce daytime sleepiness compared with the control group, but the difference between the two groups was not statistically significant. It is recommended that the antiparkinsonian drug pramipexole has definite antiparkinsonian depressive effects and can be used for the treatment of depression in Parkinson’s disease (level B recommendation) to improve depressive symptoms and reduce combined medications. the SSRI antidepressant paroxetine regular-release tablets and the 5-hydroxytryptamine noradrenaline reuptake inhibitor (SNRI) antidepressant venlafaxine extended-release capsules also have definite effects on depression in Parkinson’s disease and can be used for the treatment of depression in Parkinson’s disease. It can also be used for the treatment of depression in Parkinson’s disease (Grade B recommendation). The tricyclic antidepressants desipramine and norethindrone may improve symptoms of depression in Parkinson’s disease and may be used to treat depression in Parkinson’s disease (Class C recommendation), but should be closely monitored for cognitive decline, postural hypotension, and arrhythmias. Amitriptyline has insufficient evidence of effectiveness for depression in Parkinson’s disease and has the potential to exacerbate extrapyramidal symptoms and is not recommended. Silegiline also has potential antidepressant efficacy in patients with Parkinson’s disease (U-level recommendation). There is insufficient evidence for the efficacy of SSRI and SNRI antidepressants other than paroxetine and venlafaxine extended-release capsules, but SSRI and SNRI antidepressants can be considered for the treatment of depressive symptoms associated with Parkinson’s disease due to their milder adverse effects (U-level recommendation). 2. Anxiety: There is a lack of evidence-based medical evidence for the pharmacological treatment of patients with Parkinson’s disease with anxiety. Anxiety in patients with Parkinson’s disease is usually accompanied by depression, so antidepressant treatment can improve patients’ anxiety symptoms. For moderate anxiety, benzodiazepines such as lorazepam or diazepam can be used (U-level recommendation). However, there are some potential adverse effects to be concerned about, such as sedated state, aggravated cognitive dysfunction, and balance disturbance increasing the risk of falls. Similar to the general population, SSRI-like drugs can be used for the treatment of panic attacks, social phobia, and obsessive-compulsive symptoms in Parkinson’s disease (U-level recommendation). 3. Psychotic disorders: Compared with placebo, clozapine significantly improved the Clinical Global Impression score (CGI), Brief Psychiatric Rating Scale score (BPRS), and positive symptom scores in patients with Parkinson’s disease without adverse effects that exacerbated extrapyramidal symptoms (Level I evidence 1), and also improved motor function in some patients (Level II evidence 1). The most important adverse effect of the drug is granulocytopenia, and thus patients taking the drug should have their absolute granulocyte values reviewed periodically. 1, A double-blind, placebo-controlled study of 58 patients with Parkinson’s disease with drug-induced psychotic symptoms observed for 3 months found no significant change in BPRS scores or CGI scores in the quetiapine and placebo groups before and after treatment; the study had a 45% shedding rate, which may have affected the analysis of the results. Another study comparing the efficacy of quetiapine and clozapine in patients with Parkinson’s disease with psychotic symptoms found that quetiapine and clozapine significantly improved BPRS scores, CGI scores, and did not aggravate motor symptoms of Parkinson’s disease and could be applied to the treatment of psychotic symptoms in patients with Parkinson’s disease (Level II evidence 1). 1 double-blind, placebo-controlled study looking at the efficacy of quetiapine in patients with visual hallucinations Parkinson’s disease, the results suggested that quetiapine improved CGIS scores and BPRS hallucination sub-strip scores, suggesting that quetiapine could be used for the treatment of visual hallucinations in Parkinson’s disease, with the shortcoming that the sample size of this study was small (n=16). 2. A placebo-controlled study comparing the efficacy of olanzapine with placebo in patients with Parkinson’s disease with psychotic symptoms suggested that olanzapine did not improve psychotic symptoms in Parkinson’s disease patients and exacerbated motor symptoms in Parkinson’s disease patients (Level II evidence 2). Recommendation: Clozapine improves psychotic symptoms such as visual hallucinations and delirium in patients with Parkinson’s disease and does not aggravate motor symptoms in Parkinson’s disease. It is recommended for the treatment of psychotic symptoms accompanying Parkinson’s disease in patients with Parkinson’s disease (level B recommendation), but blood tests need to be monitored for the presence of granulocytopenia. Quetiapine improves psychotic symptoms of Parkinson’s disease without aggravating extrapyramidal symptoms and may also be considered for the treatment of psychotic symptoms in patients with Parkinson’s disease (Grade C recommendation). Olanzapine is not recommended for the treatment of psychotic symptoms in Parkinson’s disease (Grade B recommendation).