Apomorphine for Parkinson’s disease: use, dosage, benefits

It is only administered when Parkinson’s disease is more advanced, levodopa tablets are no longer sufficiently effective and fluctuations in effect lead to severe motor problems: the drug apomorphine. In the phases when the drug is no longer effective (off-phases), the motor symptoms of Parkinson’s, such as tremors or muscle stiffness, return with a vengeance. Using a very fine needle, a thin tube and a pump, the medication is continuously delivered in small quantities under the skin. In this way, excessive or insufficient spikes in the effect can be avoided.

Find out here how the dopamine agonist apomorphine works, what causes the fluctuations in effect in the treatment of Parkinson’s, how pump therapy works and what advantages it brings.

What is apomorphine?

Apomorphine is an active substance from the group of dopamine agonists. It is used to treat Parkinson’s disease in order to counteract motor symptoms in advanced stages.

Apomorphine in Parkinson’s disease: effect of the dopamine agonist

Apomorphine produces the effect in the body that the neurotransmitter dopamine would produce. This is because the dopamine agonist docks onto the same receptors (D-receptors) in the brain as that neurotransmitter. Apomorphine therefore “fools” the body into thinking that sufficient dopamine is present and triggers the corresponding reactions: The motor symptoms of Parkinson’s disease such as tremor (trembling), slowness of movement (bradykinesia) or stiff muscles (rigor) improve. In addition, non-motor problems such as sleep disorders, depressive moods, muscle pain or concentration problems are often alleviated.

Apomorphine therefore only appears to compensate for the Parkinson’s-related dopamine deficiency in the brains of those affected. Nevertheless, the effect is as if the active ingredient were doing so. The dopamine deficiency in Parkinson’s is caused by the fact that dopamine-producing nerve cells in the black substance (substantia nigra) in the midbrain increasingly die off as the disease progresses. This process is triggered by cell-damaging deposits of incorrectly folded proteins in these nerve cells.

When is apomorphine therapy indicated for Parkinson’s disease?

As a rule, neurologists rely on pump therapy with the active ingredient apomorphine when the most commonly used medication levodopa or other oral Parkinson’s drugs are no longer sufficiently effective and, despite taking them, there are often phases of reduced effectiveness (off-phases) or excessive effectiveness (on-dyskinesia) with pronounced motor symptoms. These are extremely stressful and significantly reduce the quality of life of those affected.

Causes of a too weak effect of levodopa in Parkinson’s disease

An insufficient effect of levodopa (off-phases) in later stages can have various causes:

• Dopamine is stored less and less as the disease progresses : Due to the decreasing number of dopamine-producing cells, it can no longer be stored as well and released as evenly as it was at the beginning of the disease. You need more and more levodopa (dopamine precursor) to counteract the motor fluctuations (fluctuations in motor function). Your doctor will therefore have to keep adjusting the dose to ensure that you as a patient are correctly adjusted.
• Your body gets used to the levodopa and over time no longer reacts as sensitively to it as it did at the start of treatment. The effect is lost earlier than intended by the dosage, which suddenly presents you with problems such as movement blockages (freezing) or tremors.
• Slowed gastrointestinal activity is a common consequence of dopamine deficiency. This means that the levodopa medication remains in your stomach for too long and arrives at the absorption site, the small intestine, too late (e.g. after hours) to take effect.
• Proteins from food can inhibit the effect of levodopa. This is often the case if you take your medication directly with food that contains proteins. Foods such as meat, fish or eggs can inhibit the absorption of levodopa. It is therefore important to take levodopa on an empty stomach, at least 30 minutes before a meal.
• Stress or exercise increase the need for dopamine. You are exposed to many different influences during the day. If your stress level increases in certain situations, if you exercise more than usual, if you are active in sports or if your sleep was poor, the agreed dose of levodopa may be insufficient and with it your dopamine level. Too little dopamine in the body then leads to the typical worsening of symptoms.

Causes of a too strong effect of levodopa

However, it is not only too little effect that often causes problems for advanced Parkinson’s patients. Too intense an effect can also occur. This manifests itself in uncontrollable, spontaneous over-movements (so-called dyskinesia), which can also hinder normal movements and endanger those affected by increasing the risk of falling. Apomorphine therapy can also help against these muscular cramps and incorrect postures – of the feet, for example – or against skidding or otherwise erratic movements.

Causes for the occurrence of a too strong effect can be:

• The buffer effect is worse: in later stages, excess levodopa is immediately converted to dopamine, which then also has an immediate effect. Due to the progressive loss of the dopamine-forming and storing nerve cells, it can no longer be stored as well and released evenly in the form of dopamine and is then present in too high a concentration at any given moment.
• Soluble tablets often lead to a rapid onset of action: Soluble tablets with the active ingredient levodopa or as a combination preparation with COMT inhibitors dissolve easily in the stomach and often lead to a rapid onset of action, with too much levodopa suddenly present in the body.
• Increased sensitivity of the receptors to levodopa: After prolonged use of levodopa, the dopamine receptors often react either less sensitively or significantly more sensitively to levodopa, so that the effect may be too strong even though there is not too much levodopa present.

Apomorphine pump: use in Parkinson’s disease

Pump therapy with apomorphine aims to counteract precisely these fluctuations in effect during the course of therapy with orally administered levodopa. In the first few months, Parkinson’s patients usually have to take an additional dose of levodopa in the morning. However, after a few months of pump therapy, this can often be either reduced or stopped altogether. The aim of pump therapy is to provide your body with the dopamine agonist apomorphine continuously – for 12 to 16 hours a day – via a pump. In severe cases, 24-hour pump therapy may also be necessary in order to better manage motor symptoms. But how exactly does such an apomorphine pump work?

How apomorphine therapy works

Your doctor will explain the pump therapy to you so that you can understand and use the technology. He or she will also program the pump to suit you. If pump therapy is suitable for you, treatment will be started. In contrast to L-dopa pump therapy, surgery is not necessary as no catheter needs to be inserted inside the body.

Only a wafer-thin needle is fixed to the abdomen with a plaster to hold it in place for the infusion therapy. The needle is connected to a portable pump via a thin tube. From a small container integrated into the pump, the apomorphine solution then flows continuously through the tube and needle under the skin, into the subcutaneous fatty tissue. The active ingredient must not be administered into the vein. In most cases, the needle and pump are removed at night and must be replaced the next day.

Simple operation

At 150 grams, the pump is very light and can be easily transported due to its small size. It is also easy to operate, which is an advantage for older people. You can have the ready-to-use components for infusion therapy delivered directly to your home. After comprehensive initial training by your doctor or healthcare professional, you can then use the set yourself at any time. To do this, you need to insert the cartridge into the pump, connect the infusion tube to the cartridge, disinfect the skin, allow it to dry, insert the needle and secure it. You can then switch on the pump and start the infusion. However, it is important to continue to have experienced doctors supervise the pump therapy.

Apomorphine for Parkinson’s disease: Dosage

The daily dose of apomorphine is between 30 and 100 milligrams (mg), depending on the patient, but can also be 140 mg per day in individual cases. The daily dose is divided over 12 to 16 hours. Between 1 and 8 mg is administered per hour; as a solution, this amount corresponds to between 0.2 and 1.6 milliliters per hour (ml/h).

Two different cartridge sizes are available for Parkinson’s patients who opt for this form of therapy, one with 20 ml and one with 50 ml.

Duration of treatment with apomorphine for Parkinson’s disease

There is no fixed maximum duration for the use of the drug in advanced Parkinson’s disease. According to the current Parkinson’s guideline, the efficacy has been investigated and proven for a period of five years. However, on average, treatment is discontinued after 2.5 years, either due to side effects such as hardening under the skin or because the progression of the disease requires a different treatment.

Apomorphine for Parkinson’s disease: advantages of pump therapy

Pump therapy with apomorphine is an alternative to oral therapy with levodopa in advanced Parkinson’s with frequent fluctuations in effect. We have summarized the advantages for you here:

• The continuous administration of a small amount of apomorphine can effectively counteract sudden off-phases with motor disturbances as well as excessive movements.
• Administration under the skin makes an operation with catheter placement superfluous.
• You will notice an effect very quickly. After just a few minutes, your movements may become more fluid again or your muscles less stiff.
• The pump is easy to use.
• The pump is light and small so that it can be easily stored in a bag, for example.
• The pump is robust and has a long battery life.

Apomorphine for Parkinson’s disease: side effects

The drug apomorphine helps well against the undesirable problems of mobility, such as slowness of movement, muscle stiffness or violent over-movements (on-dyskinesia). However, like other medications, it can also cause side effects. In addition to redness, swelling and lump formation under the skin at the injection site, nausea with vomiting or low blood pressure with dizziness can occur, especially in the early stages. In addition, restlessness, sleep disorders, confusion and even hallucinations, diarrhea and impulse control disorders with addictive behavior such as gambling or shopping addiction have also been observed.