Content introduction: Parkinson’s disease non-motor symptoms and treatment, Parkinson’s disease (PD) non-motor symptoms can lead to reduced quality of life of patients, and even aggravate the motor symptoms and functional disability of patients with Parkinson’s disease. Parkinson’s disease (PD) non-motor symptoms can lead to reduced quality of life and even aggravate motor symptoms and functional disability in patients with PD. In order to raise clinicians’ awareness of non-motor symptoms in Parkinson’s disease, China Medical Tribune briefly introduces the recently released guidelines for the treatment of non-motor symptoms in Parkinson’s disease by the American Academy of Neurology (AAN), as well as the guidelines for the evaluation and treatment of Parkinson’s disease-associated depression, psychiatric abnormalities, and dementia, which were released in 2006. DISORDERS OF PHYSICAL NERVOUS FUNCTION, SENSATION, AND SLEEP 1. Postural Hypotension There is a lack of randomized controlled trials of salbutamol and a-adrenergic agonists for the treatment of postural hypotension in patients with Parkinson’s disease. However, the pharmacologic effects of the above drugs are consistent with improvement in postural hypotension. Currently, the only FDA-approved drugs available for the treatment of postural hypotension are midodrine (an a-adrenergic receptor agonist) and droxidopa, which is an active synthetic precursor of orally administered norepinephrine. Recommendations on how to treat postural hypotension in patients with Parkinson’s disease are still lacking in information. 2. Erectile dysfunction A thorough medical evaluation should be performed to determine if there are treatable possible causes of erectile dysfunction such as medication side effects. The U.S. Food and Drug Administration (FDA) has approved sildenafil tartrate as a treatment for erectile dysfunction. Sildenafil tartrate is recommended for the treatment of erectile dysfunction in patients with Parkinson’s disease (grade C). 3, constipation Despite the lack of randomized controlled studies on the treatment of constipation in patients with Parkinson’s disease, the pharmacological effects and widespread clinical use of polyethylene glycol and botulinum toxin are consistent with improvement of constipation in patients with Parkinson’s disease. In addition, non-pharmacological treatments such as increasing the water and fiber content of the diet have clinical benefits in relieving constipation in patients. Many therapeutic agents can cause constipation. Polyethylene glycol is recommended for the treatment of constipation in patients with Parkinson’s disease (Grade C) The evidence for botulinum toxin for the treatment of constipation in patients with Parkinson’s disease is not yet sufficient (Grade u). 4, Urinary incontinence Although randomized controlled studies of anticholinergics for the treatment of urinary incontinence in patients with Parkinson’s disease are lacking, their pharmacological effects and widespread clinical use are consistent with improvement in urinary incontinence in patients with Parkinson’s disease. Anticholinergics may cause confusion in patients with Parkinson’s disease. Recommendations on how to treat urinary incontinence in patients with Parkinson’s disease are lacking (Grade u). 5. fatigue There is a potential for misuse of methylphenidate. Although current evidence is insufficient, patients with Parkinson’s disease do have a risk of dopamine dysregulation syndrome and impulse control disorders that have similar clinical and functional imaging features to addiction. There are no controlled studies on the treatment of sleep apnea, sleep-disordered breathing, deep sleep states, and sleepwalking. Methylphenidate is recommended for the treatment of fatigue in patients with Parkinson’s disease (89) Abnormal sleep behavior during the REM sleep phase, and the antiepileptic drugs hydroniazepam and melatonin are commonly used to treat abnormal sleep behavior during the REM sleep phase in the general population. Recommendations on how to treat sleep behavior abnormalities during REM sleep are lacking (level u). 6. Excessive daytime sleepiness It is recommended that modafinil be considered to improve the subjective perception of Parkinson’s disease patients with excessive daytime sleepiness (Level A), and there is a lack of sufficient evidence of the safety benefits of engaging in potentially hazardous activities (e.g., driving) that can be caused by sleep in Parkinson’s disease patients with excessive daytime sleepiness (Level u). It should be noted that modafinil may only improve patients’ subjective sleep perception rather than actually improving their objective sleep indicators. 7, Insomnia Currently, deep brain stimulation of the thalamic nucleus is not used to treat sleep disorders. Recommendations The benefit of levodopa on objective sleep metrics unaffected by motor status is not yet chi sufficient evidence (level u), and the evidence for melatonin treatment of poor sleep quality in patients with Parkinson’s disease is not yet sufficient (level u). 8, periodic limb movements during sleep Information on the use of dopamine agonists for the treatment of restless legs syndrome and periodic limb movements during sleep is lacking. The only FDA-approved medications currently available for the treatment of moderate-to-severe primary restless legs syndrome are ropinirole and pramipexole. Levodopa or carbidopa are recommended for the treatment of periodic limb movements during sleep, and the evidence for non-ergot alkaloid dopamine agonists for the treatment of restless legs syndrome and periodic limb movements during sleep is insufficient (level u). 9, Anxiety Although randomized controlled studies of the efficacy of anxiolytic agents in patients with Parkinson’s disease are lacking, the pharmacological effects and widespread clinical use of levodopa, among others, are consistent with improved anxiety in patients with Parkinson’s disease. Anxiolytic agents are associated with ataxia, falls, and cognitive dysfunction. Controlled studies related to the treatment of psychological symptoms (including obsessive-compulsive conceptual behaviors, gambling, delusions, decreased movement, apathy, and concentration difficulties) are lacking. 10, Depression, Psychiatric Abnormalities, and Dementia The evidence for recommending levodopa for the treatment of anxiety in patients with Parkinson’s disease is insufficient (level u). Optimal Therapeutic Drugs for Depression in Patients with Parkinson’s Disease Based on the results of a Class II study, amitriptyline may be effective in the treatment of depression associated with Parkinson’s disease. There is insufficient evidence to support or refute the effectiveness of other specific antidepressants in the treatment of depression associated with Parkinson’s disease. In patients with Parkinson’s disease, anticholinergic medications (especially tricyclic antidepressants) should be considered for their potential side effects of exacerbating cognitive deficits and causing postural hypotension (increased risk of falls). Although Parkinson’s disease generally occurs in adults, the FDA proposed in 2004 that all antidepressants should be clearly labeled as having an increased risk of suicidal ideation and suicide in tone adolescents. It is recommended that amitriptyline may be considered for the treatment of depression associated with Parkinson’s disease (Class C). Although amitriptyline has the highest level of recommendation, it does not have to be the drug of choice in the treatment of depression associated with Parkinson’s disease. There is insufficient evidence to recommend other therapeutic agents. Although the literature on the effectiveness of non-tricyclic antidepressants is lacking, this does not equate to a lack of effectiveness. Optimal Nonpharmacologic Treatment of Depression in Patients with Parkinson’s Disease There is not yet sufficient evidence to support or refute the effectiveness of transcranial magnetic stimulation technology (TMS) (one Level III study) or electroconvulsive therapy (ECT) (one Level IV study) for depression (Level u). Optimal treatment of psychiatric abnormalities in patients with Parkinson’s disease: one Class I study and one Class II study suggest that clozapine may be effective in patients with psychiatric abnormalities in Parkinson’s disease. Hydroniazepine may improve psychiatric abnormalities and lead to improvements in motor function in some patients. Quetiapine may improve mental abnormalities in patients with Parkinson’s disease. Oxytetracycline may not improve mental abnormalities and worsen motor function abnormalities in patients with Parkinson’s disease. It is important to note that, although the mechanism is unknown, all atypical antipsychotics carry a risk of slightly increasing mortality in patients with Parkinson’s disease (especially in patients with dementia who are treated for behavioral abnormalities). This would counteract the therapeutic effect of this class of drugs, balanced by the high morbidity and mortality associated with psychiatric abnormalities in patients with Parkinson’s disease. It is recommended that clozapine should be considered for the treatment of psychiatric abnormalities in patients with Parkinson’s disease (Grade B). Clozapine is associated with lethal granulocyte deficiency and therefore absolute neutrophil counts should be monitored, although monitoring may vary by country. Wowethiapine may be considered for the treatment of psychiatric abnormalities in patients with Parkinson’s disease (Grade C). Oxytetracycline should not be routinely considered for the treatment of psychiatric abnormalities in patients with Parkinson’s disease (Grade B). Most Effective Treatment for Patients with Parkinson’s Disease Dementia or Dementia with Lewy Bodies (DLB): Carboplatin Bitartrate may moderately improve cognitive function in patients with Parkinson’s Disease Dementia or DLB but worsens tremor. Donepezil hydrochloride may moderately improve cognitive function in patients with Parkinson’s disease dementia. There is insufficient evidence to support or refute the effectiveness of piracetam (grade u). It is recommended that donepezil should be considered for the treatment of Parkinson’s disease dementia (Grade B). Carboplatin bitartrate should be considered for the treatment of Parkinson’s disease dementia or DLB (Grade B).