What is the treatment for Parkinson's disease?

Treatment of Parkinson's Disease

First-Line Treatment

Levodopa/carbidopa is the most effective medication for treating Parkinson's disease and should be the first-line treatment for most patients. 1, 2, 3

Optimizing Levodopa Administration

Timing and Dietary Considerations

• Take levodopa at least 30 minutes before meals to avoid interactions with dietary proteins that reduce absorption and efficacy 1, 2

• Implement protein redistribution diet (low-protein breakfast and lunch, with normal protein intake at dinner) for patients experiencing motor fluctuations—this improves motor function and increases "ON" time 1

• Monitor for complications of protein redistribution including weight loss, micronutrient deficits, hunger before dinner, and dyskinesias 1

• Avoid strict low-protein diets as they are not supported by evidence and may lead to nutritional deficiencies 1, 2

Vitamin Supplementation

• Provide vitamin B supplementation to maintain normal homocysteine levels, as levodopa may cause hyperhomocysteinemia, especially in older patients and those with long-standing disease 1, 2

• Monitor vitamin D, folic acid, and vitamin B12 status regularly during the course of disease 1

Special Administration Situations

• For tube-fed patients on oral levodopa, interrupt enteral nutrition for at least 1 hour before and 30-40 minutes after medication administration 1

Alternative First-Line Options (Monotherapy in Early Disease)

Dopamine Agonists

Dopamine agonists can be used as monotherapy in early Parkinson's disease to delay levodopa initiation and reduce motor complications, though they are less effective than levodopa 4, 3, 5

• Pramipexole: Starting dose 0.375 mg/day, titrated to maximally tolerated dose up to 4.5 mg/day in three divided doses; provides additional benefit for depressive symptoms 6, 4, 7

• Ropinirole: Comparable efficacy to pramipexole for motor symptoms 7

• Both pramipexole and ropinirole have demonstrated reduction in the rate of loss of nigrostriatal innervation compared with levodopa on imaging studies 4

MAO-B Inhibitors

• Rasagiline 1 mg once daily: Effective as monotherapy in early Parkinson's disease, with mean improvement of 4.6 points on UPDRS compared to placebo 8

• Selegiline: Blocks dopamine reuptake and increases dopamine concentrations; can be used as initial therapy, though efficacy as sole treatment is uncertain 9, 10

Adjunctive Therapy for Advanced Disease

When to Add Adjunctive Medications

Add adjunctive medications when patients develop motor complications including "wearing-off" symptoms, dyskinesias, and "on-off" fluctuations despite optimized levodopa therapy 3, 10

Dopamine Agonists as Adjunct

• Pramipexole as adjunct: Reduces "off" time from 6 hours to 4 hours per day; allows 27% reduction in levodopa dose 6

• Rasagiline 1 mg as adjunct to dopamine agonists: Produces 2.4-point greater improvement on UPDRS compared to placebo 8

COMT Inhibitors

• Entacapone and tolcapone increase levodopa elimination half-life, decrease "off" time, and allow lower daily levodopa doses 10

• Tolcapone is more potent than entacapone but requires monitoring for hepatotoxicity 10

MAO-B Inhibitors as Adjunct

• Rasagiline and selegiline increase "on" time and improve motor symptoms when added to levodopa 10

• Selegiline can cause confusion, hallucinations, and orthostatic hypotension; avoid combination with TCAs, SSRIs, or SNRIs due to drug interactions 10

Amantadine for Dyskinesias

• Amantadine (NMDA receptor antagonist) lowers dyskinesia scores and improves motor complications when given adjunctively with levodopa 10

Managing Specific Motor Complications

For Troublesome Dyskinesias

• Reduce levodopa doses as first-line approach 1

• Add amantadine if dose reduction insufficient 10

For Medication-Resistant Symptoms

• Deep brain stimulation (DBS) of either subthalamic nucleus (STN) or globus pallidus internus (GPi) can be considered for advanced disease with motor fluctuations 1, 3

• Choose GPi over STN if there is significant concern about cognitive decline, particularly regarding processing speed and working memory 1, 2

Managing Non-Motor Symptoms

REM Sleep Behavior Disorder (RBD)

• Melatonin is the preferred first-line treatment for RBD in Parkinson's disease, especially for older patients: start at 3 mg and increase by 3-mg increments to 15 mg 11, 1, 2

• Clonazepam is effective but has significant side effects including morning sedation, gait imbalance/falls, depression, and cognitive disturbances; start at 0.25 mg in patients with neurodegenerative disease 11, 1

• Rivastigmine may be appropriate for patients with RBD and cognitive impairment refractory to other treatments 11, 1

• DBS does not improve RBD symptoms in Parkinson's disease 11, 1

Gastrointestinal Symptoms

• For constipation: Fermented milk with probiotics and prebiotic fiber, plus increased water and fiber intake 1

• Monitor for medication side effects affecting nutrition: nausea, vomiting, abdominal pain, dyspepsia, constipation, weight decrease, dry mouth, and anorexia 1, 2

Critical Monitoring and Safety Considerations

Nutritional Monitoring

• Monitor body weight regularly as increasing doses of levodopa over time are associated with higher risk for malnutrition 1, 2

• Regular nutritional and vitamin status monitoring is essential throughout disease course 1

Drug-Induced Parkinsonism Warning

• Avoid metoclopramide beyond 12 weeks due to risk of extrapyramidal signs including acute dystonic reactions, drug-induced parkinsonism, akathisia, and tardive dyskinesia 11

• Early diagnosis and rapid withdrawal of antipsychotic drugs may improve possibility of complete recovery from drug-induced Parkinsonism 11

Common Pitfalls

• Do not use opioids for chronic management despite their efficacy, due to addiction risk 11

• Avoid benzodiazepines in older adults when possible—clonazepam is on the American Geriatrics Society Beers Criteria list 11

• Watch for dopamine agonist side effects including sedation, cognitive problems, and behavioral issues that may be limiting 4