What are the diagnosis and treatment options for Parkinson's disease?

From the Guidelines

Parkinson's disease diagnosis and treatment should prioritize clinical evaluation and levodopa/carbidopa as the primary medication, with a focus on managing symptoms and maintaining quality of life. The diagnosis of Parkinson's disease is primarily based on clinical evaluation, as there is no definitive test for the condition, and neurologists look for cardinal symptoms including resting tremor, bradykinesia, rigidity, and postural instability 1. Treatment typically begins with levodopa/carbidopa (Sinemet), starting at 25/100 mg three times daily, which remains the most effective medication by addressing dopamine deficiency in the brain. For younger patients or those with milder symptoms, dopamine agonists like pramipexole (Mirapex) or ropinirole (Requip) may be used first to delay levodopa-related motor complications. MAO-B inhibitors such as selegiline (5-10 mg daily) or rasagiline (1 mg daily) can be used as early monotherapy or as adjuncts.

Some key points to consider in the diagnosis and treatment of Parkinson's disease include:

• The disease results from progressive loss of dopamine-producing neurons in the substantia nigra, leading to disruption of motor control pathways 1
• Patients with Parkinson's disease are at increased risk of malnutrition and weight loss, and nutritional status should be monitored routinely throughout the natural history of the disease 1
• Dysphagia in Parkinson's disease usually occurs in the advanced phases of the disease, although sometimes it is present at onset, and functional alterations in oropharyngeal and esophageal motility can be present in about 60-80% of patients 1
• Non-pharmacological approaches including regular exercise, physical therapy, and speech therapy are essential components of treatment
• As the disease progresses, treatment becomes more complex, often requiring combinations of medications and careful timing to manage "on-off" fluctuations, and deep brain stimulation surgery is an option for patients with medication-resistant tremor or severe fluctuations.

Overall, the goal of treatment is to manage symptoms and maintain quality of life, as current treatments do not slow disease progression, making early diagnosis and personalized treatment plans crucial 1.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Mechanism of Action Parkinson's disease is a progressive, neurodegenerative disorder of the extrapyramidal nervous system affecting the mobility and control of the skeletal muscular system. Current evidence indicates that symptoms of Parkinson's disease are related to depletion of dopamine in the corpus striatum. Administration of dopamine is ineffective in the treatment of Parkinson's disease apparently because it does not cross the blood-brain barrier However, levodopa, the metabolic precursor of dopamine, does cross the blood-brain barrier, and presumably is converted to dopamine in the brain.

The diagnosis of Parkinson's disease is based on clinical features, including resting tremor, rigidity, and bradykinetic movements. The treatment options for Parkinson's disease include:

• Levodopa 2, which is converted to dopamine in the brain and relieves symptoms of Parkinson's disease
• Carbidopa 3, which inhibits decarboxylation of peripheral levodopa and increases the availability of levodopa for transport to the brain
• Pramipexole 4, a dopamine agonist that has been shown to be effective in the treatment of early and advanced Parkinson's disease. Key points to consider when treating Parkinson's disease include:
• The goal of treatment is to relieve symptoms and improve mobility
• Treatment should be individualized based on the patient's response and tolerance to medication
• Patients may require ongoing adjustment of their medication regimen to achieve optimal control of their symptoms.

From the Research

Diagnosis of Parkinson's Disease

• Parkinson's disease is diagnosed based on history and examination, including prodromal features, characteristic movement difficulty, and psychological or cognitive problems 5
• Dopamine transporter single-photon emission computed tomography can improve the accuracy of diagnosis when the presence of parkinsonism is uncertain 5
• Diagnosis is also based on the presence of bradykinesia with tremor, rigidity, or both 5

Treatment Options for Parkinson's Disease

• Treatment is symptomatic, focused on improvement in motor and nonmotor signs and symptoms 5
• Dopamine-based therapies, such as levodopa, typically help initial motor symptoms 5, 6, 7
• Nonmotor symptoms require nondopaminergic approaches, such as selective serotonin reuptake inhibitors for psychiatric symptoms and cholinesterase inhibitors for cognition 5
• Rehabilitative therapy and exercise complement pharmacologic treatments 5, 6
• Advanced treatments, such as deep brain stimulation and levodopa-carbidopa enteral suspension, can help individuals with medication-resistant tremor, worsening symptoms, and dyskinesias 5, 6, 8

Medication Options for Parkinson's Disease

• Levodopa is the gold standard for the treatment of Parkinson's disease 6
• Other medication options include dopamine agonists, monoamine oxidase type B inhibitors, and catechol-O-methyltransferase inhibitors 6, 7
• The choice of medication depends on the individual patient's symptoms and response to treatment 6, 7, 9

Device-Based Treatments for Parkinson's Disease

• Continuous subcutaneous apomorphine infusion, levodopa-carbidopa intestinal gel infusion, and deep brain stimulation are effective treatment options for advanced Parkinson's disease patients with motor fluctuations 8
• These treatments are increasingly being used in Germany, with a rising mean age of therapy implementation and more male than female patients receiving treatments 8