INFUSION THERAPY FOR ADVANCED PARKINSON’S DISEASE: THE NEW PRODUODOPA PUMP, AND MORE

Medically Reviewed by Dr. Sony Sherpa (MBBS)
Traditional Treatment Options & Limitations
Apomorphine vs. Levodopa Infusions
Limitations, Side Effects, and Complications of Infusion Therapies
Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects movement and other bodily functions. Primarily affecting dopamine-producing neurons within the brain, the condition manifests in a range of both motor and non-motor symptoms. Although the exact cause of PD is not known yet, both genetic and environmental factors are believed to play a role. Over time, PD symptoms worsen, and the condition progresses through different stages.
Advanced Parkinson's Disease
Advanced Parkinson's disease is the later stage of PD, characterized by more severe motor and non-motor symptoms. As the disease progresses, patients experience significant challenges in managing symptoms, requiring more intensive treatments.
- Motor Symptoms: These include tremors, rigidity (muscle stiffness), bradykinesia (slowness of movement), and postural instability (balance problems). Patients may also experience dyskinesias, which are involuntary, often jerky movements that occur as a side effect of long-term dopaminergic treatment.
- Non-motor Symptoms: These include cognitive decline, sleep disturbances, depression, anxiety, and autonomic dysfunction (e.g., difficulty regulating blood pressure, temperature, or sweating). As the disease advances, these non-motor symptoms often become more pronounced, affecting a patient’s overall quality of life. Cognitive impairment can range from mild cognitive decline to dementia, while sleep disturbances, including REM sleep behavior disorder, lead to poor rest and increased daytime fatigue.
Traditional Treatment Options
Historically, the primary treatment for Parkinson's disease (PD) has been oral medications designed to augment dopamine levels in the brain or replicate its effects. These medications help alleviate motor symptoms, such as tremors, rigidity, and bradykinesia.
- Levodopa (often combined with carbidopa) is the most commonly prescribed medication for PD. Within the brain, levodopa is converted into dopamine, effectively replenishing the diminished supply of dopamine-producing cells. Carbidopa helps prevent levodopa from breaking down before it reaches the brain, allowing for a more effective treatment.
- Dopamine Agonists mimic dopamine's actions in the brain and are often used alongside levodopa, especially in the early stages of PD. These medications help reduce symptoms like tremors and rigidity.
- MAO-B Inhibitors inhibit dopamine breakdown within the brain, potentially prolonging the therapeutic effects of levodopa, especially during the early stages of PD.
- COMT Inhibitors prolong the effect of levodopa by inhibiting catechol-O-methyltransferase, the enzyme that breaks down dopamine.
Limitations of Traditional Options
These medications come with significant limitations, especially in the later stages of the disease, which can be listed as follows:
- Multiple Tablets Daily: One of the primary challenges of traditional PD treatment is the need for patients to take numerous pills throughout the day, often at specific times. This can pose significant challenges, especially for individuals experiencing cognitive decline or physical limitations.
- Wearing-Off Effect: Over time, levodopa's therapeutic effect may diminish before the next scheduled dose, resulting in a resurgence of motor symptoms. This phenomenon is particularly challenging in the advanced stages of PD, as the patient may experience periods of poor symptom control and difficulty completing daily tasks. Because PD symptoms fluctuate and are often managed with timed doses of medication, missing a dose—particularly during sleep—can lead to a "wearing-off" effect, where symptoms such as tremors and rigidity return.
- On-and-Off Phenomenon: A common issue with the long-term use of levodopa is the "on-and-off" phenomenon. In the "on" phase, medication effectively manages symptoms, but in the "off" phase, motor symptoms return. This fluctuation in symptom control can significantly impact daily functioning.
- Dyskinesias: As patients continue to take levodopa over time, they may experience dyskinesias—involuntary, jerky movements that are a side effect of prolonged levodopa use. While these movements may be less severe than the original motor symptoms, they can be disruptive and distressing.
Infusion Therapies for Parkinson’s Disease
Infusion therapy for Parkinson’s disease (PD) involves the continuous delivery of medication, typically via a pump or other infusion device, to maintain stable dopamine levels in the brain. Unlike oral medications, which can have fluctuating effects due to the absorption process and the "on-and-off" phenomena, infusion therapies aim to provide a more consistent and steady supply of dopaminergic drugs.
The primary goal of infusion therapy is to reduce the motor fluctuations and dyskinesias often associated with traditional oral medications. By administering medication directly and continuously into the bloodstream subcutaneously or through a tube (catheter) inserted into the small intestine, infusion therapies help maintain more stable dopamine levels, leading to smoother control of PD symptoms.
Infusion therapies are typically used for patients with advanced Parkinson’s disease, who experience significant motor fluctuations despite conventional oral treatment. These therapies offer several advantages over oral medications, including:
- More consistent symptom control: Continuous medication delivery prevents the swings between "on" and "off" states.
- Reduced dyskinesias: The steady infusion of medication reduces the risk of involuntary movements that occur as a side effect of fluctuating dopamine levels.
- Improved quality of life: With fewer "off" periods and more reliable symptom management, patients can better engage in daily activities and experience improved motor control.
Recent Advancement in Infusion Therapy: The Produodopa Pump
The Produodopa pump is a new and promising treatment option for advanced Parkinson’s disease (PD), offering a continuous and steady infusion of foscarbidopa and foslevodopa (a combination of carbidopa and levodopa). This system is designed to provide more stable symptom management and reduce the motor fluctuations that many patients experience with traditional oral medications.
Continuous Subcutaneous Infusion of Foscarbidopa and Foslevodopa (Vyalev)
The Vyalev system involves continuous subcutaneous infusion of foscarbidopa and foslevodopa. Unlike traditional oral medications, which require frequent dosing throughout the day, Vyalev delivers the medication steadily via a wearable pump, allowing for more consistent control of PD symptoms.
Process of Pump Implantation
The implantation of the pump involves a minor surgical procedure to insert a small catheter under the skin, typically in the abdomen, where it connects to a portable pump that can be worn discreetly on the body. The pump continuously delivers medication over a 24-hour period, effectively maintaining steady dopamine levels within the brain. Once implanted, the system is easy to manage and maintain, requiring occasional refills and monitoring by healthcare professionals.
Countries Where it Has Been Approved
The Produodopa pump has been approved in various countries, including the European Union and the United States, for use in patients with advanced Parkinson’s disease who experience significant motor fluctuations despite conventional oral therapy.
Benefits of 24-Hour Levodopa Infusion Therapy
- Steady Dopamine Levels: The continuous infusion method helps maintain more consistent dopamine levels throughout the day and night.
- Improved Motor Control and Reduced "Off" Time: One of the main advantages of the Produodopa pump is its ability to reduce "off" time, the periods when motor symptoms like tremors and rigidity reappear.
- Reduced Dyskinesias: Dyskinesias can be significantly reduced with continuous infusion therapies. With a steady supply of levodopa, the motor symptoms are better controlled, leading to fewer involuntary movements.
- No Worries About Timing Medications: With the Produodopa pump, patients no longer need to worry about taking medications on time, especially during sleep.
- Wearable and Enhanced Quality of Life: The wearable nature of the Produodopa pump offers more freedom and flexibility, thereby enhancing the patient's quality of life. The system is discreet and portable, allowing patients to continue their daily activities without being burdened by constant pill-taking or worrying about motor fluctuations.
Who is a Candidate for 24-hour Levodopa Infusion?
It is recommended for patients with advanced PD who experience significant motor fluctuations despite optimal oral therapy. Ideal candidates include those who experience:
- Frequent and disabling "off" periods: These are times when the medication is not working effectively, and the patient experiences a return of motor symptoms such as tremors and rigidity.
- Unpredictable "on" and "off" fluctuations: Patients with advanced PD often experience periods of good symptom control ("on" periods) followed by sudden worsening of symptoms ("off" periods). Continuous infusion therapy can help reduce the unpredictability of these fluctuations.
Produodopa vs Duopa
Produodopa is a newer, wearable infusion therapy option, offering the same benefits as Duopa (levodopa/carbidopa intestinal gel) but with the added convenience of being portable and subcutaneous. Duopa requires a surgically implanted tube into the intestines for medication delivery, whereas Produodopa can be delivered through a small, portable pump and subcutaneous catheter.
Produodopa vs ND0612 (levodopa/carbidopa)
ND0612 is another infusion therapy that delivers a continuous infusion of levodopa/carbidopa but involves a different delivery method, typically through a central venous catheter. Produodopa, on the other hand, is subcutaneous, which may be a less invasive option for patients, offering easier administration and greater flexibility for daily activities. Both therapies aim to provide continuous symptom control for patients with advanced PD.
Other Infusion Therapies: Procedure and Considerations
CSAI (Continuous Subcutaneous Apomorphine Infusion)
Continuous Subcutaneous Apomorphine Infusion (CSAI) delivers apomorphine, a dopamine agonist, directly into the bloodstream via a subcutaneous infusion.
Method of Delivery: The apomorphine infusion is delivered via a small pump connected to a catheter that is inserted under the skin. The pump is worn by the patient, and the infusion can be adjusted to meet individual needs.
- Rapid Onset of Action: Apomorphine has a rapid onset, providing quick relief from "off" periods.
- Convenience: The subcutaneous infusion allows for continuous medication delivery, reducing the need for frequent oral doses.
- Improved Motor Control: CSAI can offer better symptom control for patients with significant fluctuations, especially during "off" periods.
Disadvantages (Complications, Side Effects, and Contraindications):
- Skin Reactions: Injection site reactions, such as irritation or swelling, can occur.
- Drowsiness and Nausea: Common side effects include dizziness, drowsiness, and nausea.
- Complications: Risk of infection at the infusion site and catheter blockage.
- Contraindications: Patients with a history of hypersensitivity to apomorphine should avoid this therapy.
LCIG (Levodopa-Carbidopa Intestinal Gel) and CLES (Carbidopa-Levodopa Enteral Suspension)
Levodopa-Carbidopa Intestinal Gel (LCIG) and Carbidopa-Levodopa Enteral Suspension (CLES) are continuous infusion therapies that deliver levodopa and carbidopa directly to the small intestine via a tube. Method of Delivery:
- LCIG is delivered via a surgically implanted tube that connects to the small intestine. A pump provides a continuous infusion of the gel.
- CLES uses a pump to deliver the carbidopa-levodopa solution into the small intestine via a feeding tube.
Approved for 16-hour or 24-hour use (in certain cases)
- LCIG is typically used for 16-hour infusion, but 24-hour use may be recommended in certain cases to control symptoms overnight.
- CLES is designed for both 16-hour or 24-hour infusions, depending on the patient’s needs.
Advantages:
- Improved Motor Control: Offers consistent symptom control, reducing "off" times.
- Reduced Dyskinesias: Continuous infusion may also reduce involuntary movements.
- Personalized Therapy: Allows for precise control of medication delivery.
Disadvantages (Complications, Side Effects, and Contraindications):
- Gastrointestinal Issues: Patients may experience nausea, diarrhea, or constipation.
- Surgical Risks: The implantation of the feeding tube can involve surgical risks.
- Infections: Risk of infection at the insertion site and with the tube.
- Contraindications: Not suitable for patients with certain gastrointestinal conditions or those who cannot tolerate surgery.
LECIG (Levodopa-Entacapone-Carbidopa Intestinal Gel)
Levodopa-Entacapone-Carbidopa Intestinal Gel (LECIG) is an advanced infusion therapy that combines levodopa, carbidopa, and entacapone, aimed at further improving the absorption of levodopa and prolonging its effect. This therapy is typically reserved for advanced PD patients who require more consistent control of symptoms.
Method of Delivery: LECIG is delivered through a tube into the small intestine, similar to LCIG. The pump continuously administers the gel over a 16- or 24-hour period, ensuring steady medication levels.
Can Be Administered Over 16 or 24 Hours: The infusion duration can be adjusted based on the patient’s symptom severity and daily routine.
Advantages:
- Extended Symptom Control: By including entacapone, LECIG extends the action of levodopa, helping to maintain motor control over longer periods.
- Improved Symptom Relief: It may provide better symptom relief than levodopa and carbidopa alone, especially in patients with motor fluctuations.
Disadvantages (Complications, Side Effects, and Contraindications):
- Gastrointestinal Discomfort: Like other intestinal gel therapies, LECIG may cause nausea, diarrhea, or constipation.
- Risk of Infection: The implanted tube poses a risk of infection.
- Contraindications: Not suitable for patients with certain gastrointestinal disorders.
Comparing Apomorphine vs. Levodopa Infusions
When comparing apomorphine infusions to levodopa infusions (LCIG, CLES, and LECIG), there are distinct differences:
- Mode of Action: Apomorphine works as a dopamine agonist, while levodopa is a precursor to dopamine.
- Method of Delivery: Apomorphine is delivered via subcutaneous infusion, while levodopa-based therapies are delivered through enteral tubes into the intestine.
- Benefits: Both therapies improve motor control, but apomorphine is often used for rapid symptom relief during "off" periods, while levodopa-based therapies provide more consistent control over time.
- Side Effects: Apomorphine may cause drowsiness and nausea, whereas levodopa infusions may lead to gastrointestinal issues and infections at the tube insertion site.
Device Management
Patients using infusion therapy devices, whether for apomorphine or levodopa-based treatments, require proper device training and management. They need to understand how to use the pumps, adjust medication settings, and replace the devices as needed.
- Device Adjustments: Adjustments may be necessary based on the patient's symptoms and any changes in their condition. Healthcare professionals should monitor the therapy closely to ensure optimal performance.
- Frequency of Changes: Depending on the type of therapy, devices, such as pumps and catheters may need to be changed regularly (usually every 3-6 months) to prevent infection and ensure the effectiveness of the treatment.
- Infection Prevention: To reduce the risk of infection, patients should:
- Clean the injection site or catheter insertion point daily with an antiseptic.
- Use sterile equipment for catheter insertion and refilling.
- Monitor for signs of infection such as redness, swelling, or discharge, and seek medical attention promptly if infection is suspected.
General Considerations - Limitations, Side Effects, and Complications of Infusion Therapies
Infusion therapies for Parkinson's disease (PD), such as continuous subcutaneous infusion of apomorphine and levodopa-based therapies, offer patients improved symptom management, but they come with several limitations, side effects, and potential complications, as seen below:
- Complexity and Cost: Infusion therapies require patients to use specialized pumps and devices, which may involve higher costs and the need for consistent access to healthcare providers for management.
- Surgical Risks: Some infusion therapies, such as LCIG and LECIG, require surgical implantation of a tube, which carries the usual risks of surgery, including infection and complications from the procedure.
- Patient Commitment: Continuous infusion requires patients to manage the devices effectively, including ensuring proper catheter placement and maintaining consistent usage, which may be challenging for some patients.
- Restricted Mobility: While the infusion pumps are wearable, the need to carry or wear these devices could be cumbersome for some patients, limiting their mobility.
- Dyskinetic Movements: While infusion therapies can reduce "off" time, they can also result in involuntary movements (dyskinesias), particularly if the dose is not properly regulated.
- Device-Related Issues: Device malfunctions or dislodgement of the catheter can lead to reduced efficacy or complications requiring urgent medical attention.
Other Therapies for Advanced Parkinson’s Disease
Apart from infusion therapies, there are several other non-oral therapies that have been explored for the management of advanced Parkinson's disease patients who experience motor fluctuations despite medication. These therapies address various aspects of the disease, aiming for symptom relief, disease modification, or slowing progression.
Deep Brain Stimulation (DBS)
Deep Brain Stimulation (DBS) involves surgically implanting electrodes into specific regions of the brain. These electrodes are then connected to a neurostimulator device implanted under the skin in the chest. This device delivers electrical impulses to the targeted brain areas, helping to regulate abnormal brain activity associated with Parkinson's symptoms.
Gene Therapy
Gene therapy for PD involves delivering genes that can either produce dopamine or modulate the activity of specific proteins in the brain to improve motor function. This emerging therapy aims to address the underlying causes of Parkinson's disease, offering hope for long-term management or potential disease modification.
Frequently Asked Questions (FAQs)
1. What is the latest treatment for Parkinson’s?
Currently, new advancements in infusion therapies, including the Produodopa pump and the continuous infusion of levodopa, are making waves in Parkinson's treatment. These therapies offer more consistent symptom control, reducing "off" time and improving motor function. Other innovations, like gene therapy and deep brain stimulation, continue to be explored for disease modification.
2. How long can someone with Parkinson's benefit from this therapy?
The benefits of continuous levodopa infusion therapy and other infusion treatments vary based on individual response. Many patients experience significant symptom relief for several years, with some requiring adjustments as their condition progresses. However, these therapies do not slow or halt the progression of Parkinson’s disease.
3. How does 24-hour levodopa infusion therapy compare to deep brain stimulation?
Both therapies offer distinct benefits:
- 24-hour levodopa infusion therapy continuously delivers medication, effectively reducing motor fluctuations and improving overall quality of life.
- Deep Brain Stimulation (DBS) works by regulating brain activity directly through electrical impulses. While DBS can offer long-term symptom relief and be effective for patients with motor fluctuations, it involves surgical intervention, unlike infusion therapy.
The choice between DBS and infusion therapy depends on patient preference, symptoms, and the effectiveness of previous treatments.
4. Can Parkinson's be reversed with continuous levodopa?
Parkinson's disease cannot be reversed with continuous levodopa infusion or any other therapy. While these treatments effectively manage symptoms and enhance quality of life by maintaining stable dopamine levels, they do not alter the underlying disease progression. Parkinson's disease remains a progressive neurodegenerative condition, and therapeutic interventions are primarily focused on optimizing symptom management and maximizing quality of life for as long as possible.