Initially levodopa may control your symptoms well with only 2-3 daily doses. However, over time you will start to experience changes in motor and non-motor symptoms, usually around 3-4 hours after a dose of levodopa, as the medication literally wears off and symptoms re-emerge or worsen. Symptoms then typically improve 15-45 minutes after the next dose is taken. This phenomenon is called  ‘wearing off’ (also known as ‘early wearing off’).

Wearing off tends to happen more frequently as Parkinson’s disease progresses, and when it does, the control of both motor and non-motor symptoms fluctuates. As ‘wearing off’ becomes more frequent it may become increasingly difficult to control symptoms and predict when medications will be effective.

Wearing off can occur any time after starting to take levodopa, after the so-called 'honeymoon period' although it more commonly develops five or more years after the onset of motor symptoms.

What are the symptoms of wearing off?

Wearing off is very individual. In some people, motor symptoms such as tremor may be the first sign, whilst for others it might be stiffness and difficulty initiating movement. But wearing off symptoms may not be related to movement at all and may be experienced in the form of increased anxiety, fatigue, a change in mood, difficulty thinking, restlessness and sweating (non-motor wearing off).

If you notice a change in your usual symptom pattern, you should discuss this with your doctor because you may be experiencing wearing off. Your doctor will then be able to adjust your medication regime to provide better symptom control, possibly by reducing the interval between the levodopa doses and increasing the number of daily doses.

Symptoms of wearing off: an overview

Wearing Off Graph (PD medication always means levodopa)

Motor fluctuations are the changes in motor performance associated generally with taking levodopa but also with dopamine agonists in some cases. These fluctuations tend to be more prevalent in those with young-onset Parkinson’s (i.e. onset under the age of 40-50) but they might be experienced at any age.

The main factor leading to the development of motor fluctuations is the gradual loss of dopamine-producing (dopaminergic) cells that happens over time in people with Parkinson’s. This means that the level of dopamine in your brain is increasingly dependent on the availability of levodopa in the blood, which in turn relies on your most recent dose of medication.

Motor fluctuations usually appear after several years of levodopa use (long-term complications). Most people with Parkinson’s experience motor fluctuations after 5 to 10 years of levodopa treatment. However, it may only take a few months or weeks for motor fluctuations to appear if:

• you have started to take dopamine agonist medications alongside levodopa, or
• you started taking levodopa only a number of years after the onset of symptoms.

People who develop Parkinson’s before the age of 40 are also at a higher risk of developing motor fluctuations and dyskinesia (involuntary movements).

However, other symptoms (the non-motor symptoms), such as increased anxiety, fatigue, change in mood, difficulty thinking, restlessness and sweating, may also be experienced as Parkinson's progresses. Far more attention is now focused on these non-motor symptoms (the so-called 'non-motor fluctuations'), although the term ‘motor fluctuations’ has not altered so far to reflect this.

What types of motor fluctuation might I experience?

Symptoms vary from person to person and some, such as end-of-dose dyskinesia and dystonia, are less common.

Wearing off is a common sign that medication is no longer working effectively. Other signs to look out for that suggest medication is no longer as effective are outlined below.

‘On-off’ phenomenon

You may experience sudden changes in movement control, which can last for a variable period of time. These fluctuations are called the ‘on-off ‘phenomenon. 

‘On’ time is when levodopa is working well and your symptoms are controlled.  ‘Off’ time is when levodopa is no longer working well and symptoms such as tremor, rigidity and slow movement re-emerge.

As Parkinson’s progresses the ‘on-off’ swings become less closely related to the timing of a dose of levodopa. Instead it is thought that the ‘on-off’ phenomenon is related to other processes in the brain, although these mechanisms are unclear.

Delayed ‘on’

Some people experience a delay in their medication taking effect. This tends to be more noticeable with controlled-release levodopa as this can take time to dissolve in the stomach before being absorbed into the blood stream and relayed to the brain.

Freezing

Freezing is an uncontrolled and temporary inability to move which may last just a few seconds or sometimes several minutes. This tends to happen suddenly, particularly when walking, as if the feet have become stuck to the ground. Speech, writing or opening and closing the eyes can also be affected. 

If this happens you may find it difficult to judge spaces or go through narrow entrances or doorways. It can also be difficult to move from level to uneven ground, from a plain to a patterned walking surface.

Freezing tends to be more frequent as Parkinson’s progresses particularly if you take levodopa. It is less common during the early Parkinson’s and if you have not taken levodopa.

Many people experience freezing when they are ‘off’ but freezing and ‘off’ periods are not the same and require different management. If a person freezes this will only affect certain movements, whereas if they are ‘off’ they will hardly be able to move at all

For further information see Freezing.

Dyskinesia (diphasic dyskinesia) - involuntary movements

Dyskinesia is the term used to describe unintended, involuntary and uncontrollable movements. These include twitches, jerking, twisting or simple restlessness but not tremor. Whilst different parts of the body can be affected, the most common areas are the limbs and trunk. Dyskinesia affects each person differently both in its timing, frequency and severity. 

Dyskinesia generally occurs when levodopa and other dopaminergic medications are at their most effective. It is thought that an increased sensitivity to dopamine in the brain as a result of treatment, combined with the natural progression of Parkinson’s, gives rise to dyskinesia. Less commonly, dyskinesia can also occur when levodopa is just starting to take effect or when it is wearing off – this is known as ‘diphasic dyskinesia’.  

For further information see Dyskinesia.

Dystonia

It is thought that reduced dopamine levels causes the signals the brain sends to the muscles to become irregular. This causes dystonia whereby opposing muscles contract simultaneously and repeatedly over a prolonged period, leading to painful and abnormal postures, involuntary twisting and problems controlling movement. This can affect a part or all of the body and may last for a short period or for much of the day.

Dystonia is often, but not always, linked to the timing of the levodopa. ‘Off-dystonia’ can occur when the medication is ‘wearing off’. This is particularly common in the morning (before the initial morning levodopa dose) and can make it difficult to get out of bed until the next dose of medication starts to take effect. ‘On-dystonia’ can also occur when levodopa is at its highest level in the bloodstream (also known as ‘peak dose’) and dopamine levels are highest in the brain. This high level of dopamine seems to over-stimulate the muscles and cause spasms.

For further information see Dystonia.

If you think you are starting to experience wearing off or motor fluctuations, you should discuss this with your doctor promptly so that your medication can be adjusted to minimise your symptoms. Tell him or her how long your medication is lasting and what happens when it wears off. Remember to tell them about motor and non-motor symptoms.

Keeping a motor diary

You can help your doctor understand how effective your medications are by keeping diary. Typically a motor diary, or wearing off diary, will include details such as:

• the times of day when you take your Parkinson’s medication
• the times of day when you have good symptom control
• which symptoms re-emerge during the day and when
• what symptoms you experience at night
• any other complications you may experience, such as dyskinesia, and their relation to when you take your medication
• it can also be useful to note the timing of meals, drinks and snacks. Make a note of whether eating certain foods affects your symptom control – protein, for example, can interfere with the absorption of some medications.

By referring to your diary, you and your doctor will be able to see at a glance if there is a link between your symptoms and medications and if your medicines need adjusting because they are no longer providing adequate symptom control.

For a sample diary and information on keeping one see Keeping a diary.

Medication and device-aided therapies

Motor fluctuations can be tricky to treat as reducing your dose of levodopa may mean decreased fluctuations but this may also result in other symptoms returning. You will need to work closely with your doctor to get the right balance and generally try to avoid peaks and troughs of levodopa in your bloodstream. They may suggest that you take smaller but more frequent doses of levodopa, keeping the overall amount you take the same.

Your doctor may also suggest taking medications in a different way to even out the delivery of levodopa into the bloodstream, for example as an intestinal gel or a patch which provides continuous drug delivery, or subcutaneous injections/infusion which also provide continuous delivery . If your medicines cannot help levodopa work better and if your symptoms do not respond well to medication your doctor may even consider deep brain stimulation surgery. This is not suitable for everyone but in some people it can improve movement control.

For more information on these options see Types of medications and Deep brain stimulation (DBS).

Diet

For some people eating protein (such as meat, fish, eggs, cheese and beans) can cause problems by reducing gastric emptying or slowing down the amount of levodopa that is absorbed into the bloodstream. Protein is needed by the body, so it is vital not to stop eating it. However, you may find it helpful to take your medication at least 20-30 minutes before you eat to allow the medication time to start working. Some people find it useful to reduce the amount of protein they eat during the day - so that medication is more effective when it’s needed most – and eat all their daily protein in one meal at the end of the day.

However, these options are not suitable for everyone so you must talk with your doctor before altering your diet or changing the timing of your medication. They can also refer you to a dietician.

See also Eating well.

Making the most of ‘on’ time

If you experience wearing-off, it is important that your medication regime is well managed so you get the most of your ‘on’ time.

This becomes more complicated if you also begin to have dyskinesia. You might then have to decide on a compromise between more ‘on’ time with involuntary movements, or more off time with other Parkinson’s symptoms. Many people tend to prefer more ‘on’ time, even with dyskinesia, but everyone is different and you should discuss your options with your doctor or specialist.

Exercise and rest

Exercise, such as swimming or walking, may help and of course and getting plenty of sleep is important. If you find daily activities difficult when you are  ‘off ‘ then try to time these around your ‘on ‘ time so that they are easier.

Managing stress

Stress can worsen motor fluctuations so try to find time to relax. Trying to do things when you are ‘off ‘ can be frustrating and stressful so try to time activities for when medication is working well.

Complementary therapies such as yoga or Tai Chi can help with relaxation or you may find a massage helpful.

Coping strategies and tricks of movement

Many people develop their own strategies to cope with specific difficulties. Certain ‘tricks’ work for some people more than others and it is always worth trying various strategies to find the best for you.

For a wide selection of videos showing people’s coping strategies see Coping Strategies.

Other professionals who may be able to help

Your doctor may refer you to a physiotherapist or an occupational therapist. Which therapist you are referred to will depend on the country you live in, the resources available and your individual needs.

A physiotherapist can help in teaching you techniques to deal with motor fluctuation and wearing off and to improve movement, including balance, gait, posture and transfers.

For further information see Physiotherapy.

An occupational therapist will help you retain as much independence as possible in spite of your movement difficulties. They can assess your home and daily routine and can advise on adaptations at home to make movement as easy and safe as possible.

For further information see Occupational Therapy.

Content last reviewed: June 2020

We would like to thank Dr Annamária Takáts (Medical Advisor, Delta Hungarian Parkinson Association, Budapest) for her help in reviewing this information.

Our thanks to Parkinson's UK for permission to use the following source(s) in compiling this information:

• Wearing off and dyskinesia.

• VIDEO: Georg Ebersbach, MDS 2020 – Opicapone’s Potential as a First-line Adjunctive Therapy for Motor Fluctuations of Parkinson’s Disease on touchNEUROLOGY platform
• VIDEO: What is ON and OFF in Parkinson's? on Keep it ON web platform

• Poewe W, Antonini A, Chaudhuri K R, Rodríguez-Oroz M C. Beyond Motor Symptom Wearing-off in Parkinson's Disease – What Have We Learned? European Neurological Review. 2019;14(Suppl.3):2–12 – read article
• VIDEO: Recognition and management of wearing off utilisation of catechol-O-methyltransferase (COMT) inhibitors – Olivier Rascol on Oruen platform