What is wearing off?

‘Wearing off’ is a common phrase used in PD. It describes the period of time between the end of the effect of one dose of medication, and the beginning of the next one. That is, the beneficial effects of the previous dose appear to be ‘wearing off’ (see Figure, below).

Wearing off between levodopa doses

Why does wearing off occur?

There is no definite explanation for what causes wearing off. Levodopa works by supplying dopamine to the nerve cells of people with PD. However, as PD progresses, it is possible that the levodopa medication is less able to compensate for the increasing loss of dopamine-producing nerve cells. Another possibility is based on the theory that, in early PD, the extra dopamine supplied by each levodopa dose is stored and then released when needed. In more advanced PD, the dopamine can no longer be stored and so it is released all at once, beginning by working well (ON time), progressing to working too well (ON with dyskinesias), returning to working well again (ON time), and then wearing off (OFF time). These variations are examples of motor fluctuations.

What are the symptoms of wearing off?

The symptoms of wearing off vary from person to person, and may not occur after every dose of levodopa. Wearing off tends to produce a mild and gradual increase in symptoms, with some people noticing an increase in tremor or slowness. In contrast, other types of motor fluctuations associated with more advanced PD, such as those known as ON–OFF fluctuations, have more rapid and sometimes unpredictable switches between periods of good function and periods of poor function. People may experience a return of symptoms including tremor, stiffness, anxiety, depression, and pain.

Treating wearing off

As might be expected, wearing off is relieved by taking the next dose of levodopa – although there is often a delay of up to 1 hour before the medication takes effect. A doctor may be able to reduce the effects of wearing off by recommending:

• smaller, but more frequent, levodopa doses
• a different form of levodopa that releases the medication more gradually (i.e., a slow/controlled/extended-release tablet)
• chewing the levodopa tablets or taking them with carbonated drinks to increase the speed of their effect
• not taking levodopa with meals (food slows its action)
• treating constipation (levodopa is absorbed just beyond the stomach and, if a person is constipated, the dose may stay in the stomach for several hours, unable to work)

An alternative option is to add another medication (MAO-B inhibitor, dopamine agonist, or COMT inhibitor) to minimise the wearing off symptoms. The addition of this second medication is known as adjunct or combination therapy.

It is clear that treatment of motor fluctuations is a complicated process, and therefore doctors tailor the treatments for each individual. For this reason, it is sometimes helpful if the person with PD keeps a daily diary of their symptoms and the effects of medication, noting any variations during the day. This gives the doctor extra information when recommending a therapy, and saves the person from having to remember these details from visit to visit. Follow the link to ‘Wearing off diary’ to find a template for a daily diary that can be printed off and used to record symptoms every day.