From the Guidelines
Parkinsonism is a complex neurological syndrome that requires a multifaceted approach to management, focusing on addressing the underlying cause, managing symptoms, and improving quality of life, with the most recent and highest quality evidence suggesting that early diagnosis and treatment are crucial to slow functional decline and improve morbidity, mortality, and quality of life 1.
Causes of Parkinsonism
The causes of parkinsonism are diverse and include:
- Parkinson's disease, resulting from the degeneration of dopamine-producing neurons in the substantia nigra of the brain
- Medications, such as antipsychotics and some anti-nausea drugs
- Repeated head trauma
- Vascular disease affecting the brain
- Toxin exposure, such as manganese or carbon monoxide
- Certain neurodegenerative disorders like progressive supranuclear palsy and multiple system atrophy
Treatment of Parkinsonism
Treatment primarily focuses on addressing the underlying cause when possible and managing symptoms. For Parkinson's disease, medications that increase dopamine levels or mimic dopamine's effects are the mainstay of treatment, including:
- Levodopa, usually combined with carbidopa to prevent side effects
- Dopamine agonists like pramipexole and ropinirole
- MAO-B inhibitors such as selegiline and rasagiline
- COMT inhibitors like entacapone Treatment typically begins with lower doses that increase gradually based on symptom control. For medication-induced parkinsonism, discontinuing the offending drug often resolves symptoms.
Non-Pharmacological Approaches
Physical therapy, exercise, and occupational therapy are important non-pharmacological approaches that help maintain mobility and independence. In advanced cases unresponsive to medication, surgical options like deep brain stimulation may be considered, as it has been shown to improve motor symptoms and quality of life in patients with advanced Parkinson's disease 1.
Nutritional Management
Nutritional management is also crucial in the treatment of Parkinson's disease, with a focus on maintaining a healthy weight and preventing malnutrition, as weight loss is a common feature of the disease and can exacerbate symptoms 1. Vitamin supplementation, particularly vitamin D, may also be beneficial in slowing disease progression and improving bone health 1.
From the FDA Drug Label
Parkinson's disease is a progressive, neurodegenerative disorder of the extrapyramidal nervous system affecting the mobility and control of the skeletal muscular system. Its characteristic features include resting tremor, rigidity, and bradykinetic movements. Current evidence indicates that symptoms of Parkinson's disease are related to depletion of dopamine in the corpus striatum. Many of the prominent symptoms of Parkinson’s disease are due to a deficiency of striatal dopamine that is the consequence of a progressive degeneration and loss of a population of dopaminergic neurons which originate in the substantia nigra of the midbrain and project to the basal ganglia or striatum
The causes of Parkinsonism are related to:
- Depletion of dopamine in the corpus striatum
- Progressive degeneration and loss of dopaminergic neurons The treatment of Parkinsonism may include:
- Levodopa therapies, which permit the patient better mobility
- Carbidopa, which inhibits decarboxylation of peripheral levodopa and increases the bioavailability of levodopa
- Selegiline, a selective monoamine oxidase type B inhibitor, which may increase the net amount of dopamine available by blocking its catabolism 2 3
From the Research
Causes of Parkinsonism
- Parkinsonism is a neurological disorder that can be caused by various factors, including genetics, environmental factors, and certain medical conditions 4
- The exact cause of Parkinson's disease is still unknown, but it is believed to involve the death of dopamine-producing neurons in the brain 5
Stages of Parkinson's Disease
- Parkinson's disease has three stages of development: early, middle, and advanced 4
- The early stage is characterized by the onset of symptoms to the appearance of motor fluctuations, while the middle stage is marked by motor fluctuations to the appearance of moderate-to-severe disability 4
- The advanced stage is characterized by moderate-to-severe disability 4
Treatment of Parkinson's Disease
- The medical treatment of early Parkinson's disease should be started when functional disability appears, which is a different threshold for each patient 4
- For patients below 65 years old, or above 65 years old but with preserved mental function and with no severe comorbidity, initial monotherapy with a dopamine agonist is advisable 4
- Dopamine agonists have similar efficacy, which is less than that of levodopa, and the choice of a specific drug is sometimes dictated by the patient's symptoms 4, 5
- Levodopa is the "gold standard" of treatment, but it is often used in combination with other medications to minimize side effects and maximize efficacy 6, 5
- Monoamine oxidase type-B inhibitors, such as selegiline and rasagiline, have also been shown to be effective in treating Parkinson's disease, especially when used in combination with levodopa 7
Comparison of Treatment Options
- A study comparing the effectiveness of dopamine agonists and monoamine oxidase type-B inhibitors found that all the investigated drugs were effective compared with placebo when given as monotherapy, except safinamide 7
- The study also found that selegiline and rasagiline were effective for treating Parkinson's disease, and selegiline was the best option in combination with levodopa among all the drugs investigated 7
- Another study found that levodopa-sparing therapy, such as dopamine agonists and monoamine oxidase type-B inhibitors, was associated with a higher risk of side effects and discontinuation of treatment compared with levodopa alone 6
Initiating Therapy for Parkinson's Disease
- Accurate diagnosis and individualized assessment of the risks and benefits of available antiparkinsonian medications should guide initiation of treatment for patients with early Parkinson's disease 8
- The primary initial medication choices for patients under age 50 years include selegiline, amantadine, and anticholinergic agents, while patients in their fifties may require a dopamine agonist in addition to or instead of selegiline 8
- For older patients, sustained-release carbidopa-levodopa is considered first-line treatment, and anticholinergic agents, amantadine, and selegiline should be avoided due to their CNS effects 8