Parkinson’s medications

Levodopaphobia refers to the fear or reluctance to start or continue levodopa treatment, a cornerstone medication for managing Parkinson’s for nearly 60 years. It remains the most effective medication for managing motor symptoms such as tremor, stiffness and slowness of movement. Yet, despite its proven benefits, some people hesitate to start levodopa due to concerns about potential side effects.

Recent studies show that starting levodopa earlier does not increase the risk of dyskinesia or speed up disease progression. In fact, delaying levodopa until symptoms become more severe may lead to poorer symptom control and overall reduced quality of life. The American Academy of Neurology recommends levodopa as the preferred first-line treatment for motor symptoms in early Parkinson’s, due to its superior effectiveness compared to other options.

Causes of Levodopaphobia

• Myth: Many people with Parkinson’s worry about potential side effects of levodopa, such as dyskinesia (involuntary movements), which are more common with long-term use (Thanvi et al., 2007). Truth: Levodopa dose can be adjusted to minimise risk, and when it does occur, dyskinesia is usually manageable, or a preference of being “on” with dyskinesia rather than “off” and unmedicated.
• Myth: Levodopa becomes less effective over time. Truth: Levodopa works just as well chemically throughout progression… it always makes dopamine. What changes is the brain’s ability to use it smoothly as more neurons are lost. This is a reason to optimise how we deliver it (extended-release preparations, COMT inhibitors, MAO-B inhibitors, continuous intestinal infusion), not a reason to delay starting it or stop using it.
• Myth: Taking levodopa early will make me “run out of options” later in life. Truth: There is no evidence that delaying levodopa in YOPD preserves future treatment options or improves long-term outcomes. Patients have access to more advanced therapies now than ever before, and DBS works particularly well in younger patients. Unnecessary delay causes real, avoidable suffering when trying to struggles to work, parent, and maintain relationships.

Impact on people living with young onset Parkinson’s

For those with YOPD, levodopaphobia can be particularly challenging. Younger people often face unique life-stage pressures, such as managing careers, raising families, caring for elderly parents and maintaining social activities. Avoiding levodopa can lead to poorly managed symptoms, which may interfere with these responsibilities and reduce participation in things that make their life enjoyable and increase wellbeing. It may also lead to early retirement, when symptom management may be the key to remaining in the workforce longer.

Addressing Levodopaphobia

• Providing accurate information about levodopa’s benefits early on in the progression and addressing misconceptions can help alleviate fears.
• Tailoring medication plans to each person’s needs and concerns can improve sticking to the plan and better symptom control outcomes.
• Connecting with your care team, support groups, and participating in conferences and online discussions put on by trusted organisations like Parkinson’s Australia can provide reassurance and guidance.

You should seek medical advice in relation to medicines and use only as directed by a healthcare professional. Always read the label. 

1. Dopamine Precursor (Levodopa)

Dopamine-producing cells in the brain die off in Parkinson’s, which leads to motor symptoms (just like a diabetic no longer produces insulin). Levodopa is the “gold standard” medication that helps by turning into dopamine once it reaches the brain. But there’s a catch—it needs neurons there to soak it up and it doesn’t last long in the body, so starting early and optimising your medication schedule is key: “Meds on time, every time.”

To make levodopa more effective, it’s combined with a helper drug called a dopa decarboxylase inhibitor (DDI). This ensures more Levodopa reaches the brain. Common DDIs include Carbidopa (found in Kinson®) and Benserazide (in Madopar®). For example, Kinson® 125 contains 100 mg of Levodopa and 25 mg of Carbidopa.

• What it treats: Levodopa is the most effective medication for managing Parkinson’s motor symptoms, including tremor, rigidity, and slow movement. It’s often referred to as the “gold standard.”
• How it works: Levodopa converts into dopamine in the brain, replenishing the levels lost due to Parkinson’s; kind of like insulin is replaced for people living with diabetes.
• Potential side effects: Common side effects include nausea, low blood pressure, and dizziness. Long-term use may cause dyskinesias (involuntary movements), though not everyone will experience side effects.

2. Dopamine Agonists (Dopamine Mimics)

Think of these drugs as imitators—they mimic dopamine by stimulating the same receptors in the brain. Common ones include Pramipexole (Sifrol) and Rotigotine patches (Neupro). They’re sometimes used in the early stages to delay starting Levodopa or alongside Levodopa to enhance its effect.

• What it treats: These drugs help improve motor symptoms and are sometimes used early to delay starting Levodopa or alongside Levodopa for enhanced motor control (tremor, stiffness, slowness). Dopamine agonists are also commonly used to effectively reduce the uncomfortable sensations and the urge to move the legs, Restless Legs Syndrome (RLS).
• How they work: Dopamine agonists mimic dopamine by stimulating the brain’s dopamine receptors.
• Potential side effects: Possible side effects include fatigue, nausea, and hallucinations. They can also increase the risk of impulse-control disorders (e.g., hypersexuality, compulsive shopping, gambling, hobbying or eating). If these ICDs occur, tell your GP immediately and get a guided adjustment to your medications. Never stop a medication without support from your health care professional.

3. Inhibitors

• Monoamine Oxidase-B (MAO-B) Inhibitors: These medications work by stopping an enzyme (monoamine oxidase-B) that breaks down dopamine. The result? More dopamine sticks around in your brain. Common options include Rasagiline (Azilect) and Safinamide (Xadago). They can improve motor symptoms and may be easier to tolerate than dopamine agonists.
  • What it treats: MAO-B inhibitors can help manage motor symptoms and motor fluctuations. Some people prefer these for their potential to be better tolerated than other medications.
  • How they work: These drugs block an enzyme that breaks down dopamine, increasing its availability in the brain.
  • Potential side effects: Mild nausea, headaches, and insomnia are possible side effects. They may also interact with certain foods or medications.
• Catechol-O-methyltransferase (COMT) Inhibitors: COMT inhibitors stop dopamine from breaking down too quickly in the body, giving Levodopa a longer-lasting effect. Examples include Entacapone (Comtan) and Opicapone (Ongentys). Some medications, like Stalevo, even combine Levodopa, a DDI, and Entacapone all in one.
  • What it treats: COMT inhibitors are used to enhance the effect of Levodopa and reduce motor fluctuations.
  • How they work: These medications prevent the breakdown of dopamine in the body, extending Levodopa’s effectiveness.
  • Potential side effects: Side effects can include diarrhoea, orange urine discolouration, and abdominal discomfort.

5. NMDA antagonists

Amantadine (Symmetrel or Amantamed) can help with involuntary movements (dyskinesias) that might be caused by long-term levodopa use. It’s usually used alongside other medications.

• What it treats: Amantadine is often prescribed to reduce dyskinesias (involuntary movements) caused by prolonged levodopa use.
• How it works: It’s thought to increase dopamine release and block glutamate receptors to reduce motor symptoms.
• Potential side effects: Potential side effects include swelling in the legs, blurred vision, and confusion.

6. GABA-B receptor agonists mimics the action of GABA which helps reduce nerve signals that cause muscles to tighten. These uses are still experimental and not yet part of standard Parkinson’s treatment.

• What it treats: Motor symptoms by reducing overactive signalling in motor pathways. Some studies suggest they may help reduce involuntary movements (dyskinesia) Ncaused by long-term levodopa use. There is also interest in whether these drugs could help protect dopamine-producing neurons from damage.
• How it works: In Parkinson’s, where dopamine loss leads to abnormal signalling in motor circuits, GABA-B agonists may help restore balance by reducing excessive activity in certain brain regions, modulating neurotransmitter release, potentially protecting neurons from degeneration
• Potential side effects: Potential side effects include drowsiness or sedation, dizziness, muscle weakness, confusion or memory issues, low blood pressure.

7. Anticholinergics block acetylcholine, which becomes relatively overactive in the brain.

• What it treats:
  • Tremor, especially resting tremor that doesn’t respond well to levodopa.
  • Drooling (sialorrhea) by reducing saliva production.
  • Mild dystonia, in some cases, they may help reduce muscle cramping or stiffness.n.b. They are not effective for slowness of movement (bradykinesia), rigidity, or postural instability.
• How it works: Anticholinergics block the action of acetylcholine, a brain chemical that becomes relatively overactive when dopamine levels drop in Parkinson’s. By restoring the balance between dopamine and acetylcholine, these medications can help reduce tremor and other involuntary movements.
• Potential side effects: May include memory problems or confusion, dry mouth, blurred vision, constipation, urinary retention, drowsiness or dizziness. Because of these potential risks, anticholinergics are used cautiously in people over 65 or those with dementia.