What is the management of Parkinson's disease (PD)?

Management of Parkinson's Disease

Levodopa/carbidopa is the most effective medication for treating Parkinson's disease and should be the first-line treatment for most patients, with strategies to maximize its effectiveness including proper timing of medication and protein redistribution for patients experiencing motor fluctuations. 1

Initial Pharmacological Management

• Levodopa, the metabolic precursor of dopamine, crosses the blood-brain barrier and is converted to dopamine in the brain, which is the primary mechanism for relieving symptoms of Parkinson's disease 2
• Carbidopa inhibits peripheral decarboxylation of levodopa, reducing the amount of levodopa required by about 75% and decreasing levodopa-induced nausea and vomiting 3
• Take levodopa medications at least 30 minutes before meals to avoid interactions with dietary proteins that reduce absorption and efficacy 1, 4
• For patients with mild symptoms, tremor as the only prominent symptom, or those under 60 years of age, consider starting with MAO-B inhibitors (like selegiline), amantadine, anticholinergics, β-blockers, or dopamine agonists to delay levodopa-related motor complications 5, 6
• Selegiline (MAO-B inhibitor) can be used at a dose of 10 mg/day without dietary restrictions in most patients, but monitoring for potential hypertensive reactions is still recommended 7

Managing Motor Fluctuations

• For patients experiencing motor fluctuations (transitions between "ON" and "OFF" states), implement a protein redistribution diet (low-protein breakfast and lunch, with normal protein intake at dinner) to improve motor function 4, 1
• More than 85% of patients can achieve complete remission of motor symptoms with low-dose carbidopa/levodopa, while approximately 10% can achieve partial control (frequency reduced by at least 75%) 4
• Consider adding MAO-B inhibitors, catechol-O-methyltransferase (COMT) inhibitors, or dopamine agonists for patients with persistent motor fluctuations 6
• Reduce levodopa doses for patients with troublesome dyskinesias 1
• For advanced Parkinson's disease with medication-resistant symptoms, consider deep brain stimulation (DBS) of either subthalamic nucleus (STN) or globus pallidus internus (GPi) 1, 8

Nutritional and Swallowing Management

• Monitor for side effects of PD medications that might influence nutritional status, including nausea, vomiting, abdominal pain, dyspepsia, constipation, weight decrease, dry mouth, and anorexia 1
• Implement rehabilitation treatment for dysphagia, including adapting bolus characteristics, postural maneuvers, and exercise programs after multidimensional assessment of swallowing function 4
• For tube-fed patients on oral levodopa, interrupt enteral nutrition for at least 1 hour before and 30-40 minutes after medication administration 1
• Pudding-thick liquids may result in safer swallowing (lower penetration-aspiration scores) for people with PD and dysphagia, despite causing significantly higher oral transit time 4
• Patients with constipation may benefit from fermented milk with probiotics and prebiotic fiber, in addition to increased water and fiber intake 1

Managing Non-Motor Symptoms

• For REM sleep behavior disorder (RBD) in PD, consider clonazepam (with awareness of side effects including morning sedation, gait imbalance/falls) or melatonin (starting at 3 mg and increasing by 3-mg increments to 15 mg) 1
• Rivastigmine may be appropriate for patients with RBD and cognitive impairment refractory to other treatments 1
• Cholinesterase inhibitors may improve symptoms of dementia, while antidepressants and pramipexole may improve depression in PD patients 6
• Monitor for hyperhomocysteinemia in patients on levodopa therapy, especially in older patients and those with long-standing disease, and consider vitamin B supplementation 1, 4
• Regular monitoring of nutritional and vitamin status is recommended, with particular attention to changes in body weight and the need for vitamin D, folic acid, and vitamin B12 supplementation 1

Advanced Treatment Options

• For patients with medication-resistant tremor, worsening symptoms when medication wears off, and dyskinesias, consider advanced treatments such as levodopa-carbidopa enteral suspension or deep brain stimulation 5
• Levodopa/carbidopa intestinal gel infusion through percutaneous endoscopic gastrojejunostomy and a portable infusion pump can reduce "off" time and increase "on" time 9
• Patients with cognitive concerns may benefit from GPi rather than STN deep brain stimulation if advanced therapy becomes necessary 1
• Palliative care should be integrated into the management of Parkinson's disease, particularly in advanced stages 5

Common Pitfalls and Caveats

• Avoid strict low-protein diets as they are not supported by evidence 1
• Monitor for potential complications of protein redistribution, including weight loss, micronutrient deficits, hunger before dinner, and dyskinesias 1, 4
• Increasing doses of levodopa over time are associated with a higher risk for malnutrition, requiring careful monitoring 1
• Surface electrical stimulation, repetitive transcranial magnetic stimulation, or video-assisted swallowing therapy have insufficient evidence to make strong recommendations for dysphagia management 4
• Be aware that selegiline's metabolites (amphetamine and methamphetamine) have pharmacological actions of their own and may contribute to side effects 7