Medications for Parkinson’s disease

Overview

Medications for Parkinson’s disease (PD) primarily aim to manage symptoms, as there is currently no cure for this condition. Levodopa is the most commonly prescribed medication; however, many patients find that effective symptom control often requires a combination of drugs.

Parkinson’s disease is a progressive neurological disorder that impacts movement and various bodily functions, including the sense of smell, sleep patterns, and digestion. The condition results from the degeneration of nerve cells, particularly in the substantia nigra, a brain region essential for movement control. As these cells become damaged or die, they lose their ability to produce dopamine, a crucial neurotransmitter that regulates movement.

Types

Most Parkinson’s disease medications focus on regulating dopamine levels or other neurotransmitters that influence dopamine. Most individuals with PD require a combination of medications.

• Levodopa and carbidopa: Levodopa is the primary medication used to treat Parkinson’s disease, functioning as a dopamine replacement agent. It effectively crosses the blood-brain barrier (BBB) and is converted into dopamine within both the central and peripheral nervous systems.

However, before reaching the brain, most of the levodopa is metabolized by blood enzymes. To enhance its effectiveness, levodopa is paired with carbidopa, an enzyme inhibitor that increases the amount of levodopa that reaches the brain and minimizes severe nausea and vomiting, which are frequent side effects of using levodopa alone.

For the majority of patients, levodopa alleviates symptoms such as slowness (bradykinesia), stiffness, and tremors, proving particularly beneficial for those experiencing a loss of spontaneous movement and muscle rigidity.

Brand names for the combination of levodopa and carbidopa include:

• • Dhivy
  • Parcopa
  • Rytary
  • Sinemet
• Dopamine agonists: For patients who are younger or who are in the early stages of Parkinson’s disease, healthcare providers may suggest a dopamine agonist. These medications may increase the efficiency of levodopa by activating dopamine receptors in the brain. Typical Parkinson’s disease prescriptions for dopamine agonists include:
  • Pramipexole (Mirapex).
  • Ropinirole (Requip).
  • Rotigotine (Neupro).
• Enzyme inhibitors: Enzyme inhibitors, such as MAO-B inhibitors and COMT inhibitors, work by slowing down the enzymes that break down dopamine in the brain, thereby increasing the availability of dopamine.
  • MAO-B inhibitor: These medications include selegiline (Carbex, Eldepryl) and rasagiline (Azilect). These medications reduce the activity of the enzyme that metabolizes dopamine, delaying the breakdown of both naturally occurring dopamine and that produced from levodopa. Providers may prescribe these alongside levodopa to enhance and prolong its effectiveness.
  • COMT inhibitors: These may include entacapone (Comtan) and opicapone (Ongentys), are typically prescribed to extend the duration of levodopa’s effects.
• Amantadine: Healthcare providers may recommend amantadine (Osmolex, Gocovri, Symmetrel) to assist relieve dyskinesia, which is a condition in which twitching or writhing movements can be brought on by dopaminergic medications.

While amantadine is primarily an antiviral medication, its antiviral properties are not responsible for its effectiveness in managing dyskinesia. The exact mechanism by which amantadine minimizes these symptoms remains unclear to researchers.

In addition to dyskinesia, amantadine is also used to treat other movement-related symptoms of Parkinson’s disease, such as abnormal muscle activations leading to dystonia.

• Anticholinergic medications: These can help alleviate tremors and muscle rigidity by blocking the action of acetylcholine, a neurotransmitter whose effects become more pronounced when dopamine levels decrease. Your healthcare providers may prescribe anticholinergic medications such as:
  • Benztropine mesylate (Cogentin).
  • Trihexyphenidyl (Artane).
• Adenosine A2A antagonists: Istradefylline (Nourianz), a non-dopaminergic medication, can assist manage motor symptoms, especially when symptoms recur in between doses of dopaminergic therapy. Researchers think it improves the effects of dopamine, leading to improved symptom control, albeit the precise mechanism is unknown.
• Other medications: Parkinson’s disease can lead to non-motor symptoms, and your healthcare provider may prescribe medications to address these specific issues. Some of these include:
  • Antipsychotic medications, such as pimavanserin, for addressing psychosis-related symptoms like hallucinations.
  • SSRIs (selective serotonin reuptake inhibitors) to treat depression and/or anxiety.
  • Cholinesterase inhibitors to manage dementia symptoms.
  • Modafinil for managing daytime sleepiness (hypersomnia).
  • Methylphenidate to combat fatigue.
  • Polyethylene glycol for relieving constipation.
  • Sildenafil for treating erectile dysfunction.

Risks

The potential side effects associated with Parkinson’s disease medications vary depending on the type. Additionally, combining certain medications may lead to different side effects. It’s important to discuss these side effects with your healthcare provider before beginning any treatment.

Common side effects of Levodopa include:

• Daytime sleepiness.
• Dizziness.
• Headache.
• Nausea and vomiting.
• Postural hypotension (low blood pressure).

In older individuals taking levodopa, the most common side effects include:

• Agitation.
• Confusion.
• Delusions (strongly held untrue beliefs).
• Hallucinations.
• Psychosis.

Sudden discontinuation or dose reduction of levodopa can significantly increase the risk of parkinsonism hyperpyrexia syndrome, a potentially fatal condition that resembles neuroleptic malignant syndrome (NMS).

Dopamine agonist side effects:

• Confusion.
• Drowsiness.
• Dizziness.
• Delusions.
• Hallucinations.
• Dry mouth.
• Nausea and vomiting.
• Feeling faint upon standing.

When starting a dopamine agonist, these side effects are frequent but generally diminish after a few days. However, in older adults, these medications have a higher likelihood than levodopa of causing confusion, hallucinations, or psychosis. As a result, healthcare providers are less inclined to prescribe them for elderly patients.

• Enzyme inhibitor side effects
  • COMT Inhibitors
    • Diarrhea
    • Dyskinesia
  • MAO-B Inhibitors
    • Nausea.
    • Dry mouth.
    • Heartburn.
  • Dizziness.

Rare side effects of selegiline may involve confusion, nightmares, and hallucinations.

• Amantadine side effects
  • Agitation.
  • Difficulty concentrating.
  • Confusion.
  • Insomnia.
  • Nightmares.
  • Hallucinations.
  • Leg swelling.
• Anticholinergic medication side effects
  • Blurred vision.
  • Cognitive deficits.
  • Delirium.
  • Hallucinations.
  • Sleepiness (sedation).
  • Dry mouth.
  • Constipation.
  • Urinary retention.

Outcome

Parkinson’s disease medications mostly offer effective symptom management for three to six years. However, as the disease progresses, your body’s response to these treatments may weaken.

The way your body reacts to Parkinson’s medications can depend on several factors, including:

• Age.
• How early the condition was diagnosed and treatment began.
• The overall health.

Adhering to your prescribed medication schedule and following your healthcare provider’s instructions are important. Report any side effects to your healthcare provider and avoid stopping medications without consulting them first.

Researchers and healthcare providers are continuously developing new dosing strategies for levodopa and other medications to extend their effectiveness. Ongoing research is also aimed at discovering treatments that could slow the progression of Parkinson’s disease.

Alongside prescription medications, additional treatments such as physical therapy can play a vital role in managing Parkinson’s disease symptoms.

Individuals with Parkinson’s who engage in a structured physical therapy program specifically designed for the condition often experience better symptom control and enhanced quality of life. Physical therapy can assist you in:

• Enhancing balance and gait (walking pattern).
• Improving stability.
• Maintaining an active lifestyle.

Regular physical activity is crucial for managing Parkinson’s disease, as it is the only intervention proven to slow the progression of the condition. Individuals with Parkinson’s are encouraged to aim for at least 150 minutes of cardiovascular exercise each week.

If you are experiencing distress, depression, or anxiety related to your condition, it is important to seek support from a mental health professional, such as a psychologist, since Parkinson’s can significantly affect your mental well-being.

Routine appointments with your healthcare provider are essential when taking medications for Parkinson’s disease. These visits allow for the evaluation of your treatment’s effectiveness and help address any new symptoms that may arise.

You should communicate with your healthcare provider if you:

• Experience bothersome side effects.
• Notice that your symptoms are not improving or have worsened.
• Are considering discontinuing your medication.