What causes wearing-off?

When a person suffering from Parkinson’s disease experiences wearing-off, it is thought to be caused by the progression of the disease and a reduction in the time that it takes the body to break down levodopa. A patient experiencing wearing-off may feel that levodopa is becoming less effective.

Wearing-off is thought to be caused by the progression of Parkinson’s disease and a reduction in the time that it takes the body to break down levodopa. Levodopa becomes less effective over time because the patient’s levels of dopamine start to become more variable. Levodopa is converted to dopamine, which is stored in the nerve cells. In the early stages of the disease, the nerve cells function as buffers for the dopamine, but in the later stages of the disease, there are fewer nerve cells, so they are unable to act as buffers, taking up and storing dopamine, as well as before. The patient feels as though the levodopa is becoming less effective.

The initial symptoms of wearing may be quite subtle and to begin with, may not occur after every dose, or even every day. Because wearing-off affects daily life, many consider it to be one of the greatest challenges of Parkinson’s disease.

Symptoms of wearing-off

The symptoms affecting movement are easy to notice with wearing-off. It is characteristic for the symptoms associated with wearing-off to improve after the next dose is taken and to re-appear before the following dose is taken. Other symptoms, such as mood swings, pain, panic attacks or slowness of thinking may also be an indication that the medication is becoming less effective, but these symptoms may be difficult to identify.

The patient’s description of symptoms is used to identify wearing-off. The patient’s doctor will assess whether the symptoms are caused by wearing-off on the basis of this description and a physical examination. The wearing-off questionnaire can help to identify the symptoms.

How common is wearing-off?

Early on in the disease, levodopa is very effective, with constant results from one dose to the next. However, it is fairly common for the effects to gradually start weakening from 2 to 5 years after starting the treatment, and sometimes sooner. Almost 50% of people with Parkinson’s disease will start to develop the symptoms of wearing-off within a few years and almost 90% of patients will develop them after 15 years. The symptoms of wearing-off can be treated with products containing active pharmaceutical ingredients that lengthen the effects of levodopa or by supplementing the levodopa with other forms of treatment.