It is important to remember that the symptoms you experience may not be the same symptoms as others experience. The following are the most common ones to look out for when medication is no longer as effective:
Wearing off
A dose of levodopa that initially removed symptoms for four hours may not provide enough dopamine to maintain full control of symptoms until the next dose, and so ‘wearing off’ (also known as ‘early wearing off’) may be experienced and symptoms re-emerge before the next dose is due. These symptoms then typically improve 15-45 minutes after taking the next dose of medication.
As ‘wearing off’ becomes more frequent it may become increasingly difficult to control symptoms and predict when medication will be effective.
For further information see Wearing Off.
“On-off” phenomenon
About 15% of people on levodopa experience random and sudden changes in motor performance, which can last for a variable period of time. These fluctuations are called the “on-off” phenomenon.
“On” time is the period when levodopa is working well and symptoms are successfully controlled. “Off” time is when levodopa is no longer working well, another dose is due/required and symptoms such as tremor, rigidity and slowness (bradykinesia) re-emerge.
Unfortunately, the cause of the rapid change from good (“on”) to poor (“off”) symptom control can be complicated to treat, particularly as this phenomenon isn’t exclusively affected by levodopa; in fact as Parkinson’s progresses the “on-off” swings become less closely related to the timing of the levodopa dose. Instead it is believed that the “on-off” phenomenon is related to other processes in the brain, although doctors are not entirely sure of their interaction.
Delayed “on”
Some people experience a delay in their medication being effective. This tends to be more noticeable in controlled-release levodopa as this medication can take some time to dissolve in the stomach before being absorbed into the blood stream and relayed to the brain.
Freezing
Freezing is a temporary, involuntary inability to initiate or continue movement lasting just a few seconds or, on some occasions, several minutes. It is one of the most disabling and least understood symptoms in Parkinson's and happens 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.
Some people with Parkinson’s find it difficult to judge spaces and they may struggle with narrow entrances or doorways, or stepping from a level to uneven ground, or moving from a plain to a patterned walking surface. But rather than the brain automatically adjusting the stride to cope with the situation, the person has to consciously think through the steps. It is this interruption of movement that is thought to trigger freezing.
Freezing tends to occur with increased frequency as Parkinson’s progresses particularly in those who take levodopa (although some research has shown that freezing can occur during the early stages of Parkinson’s in those who are not treated with levodopa). Many experience freezing when they are “off”. However, it is important to recognise that that freezing and ‘off’ periods are separate phenomena requiring different management.
Visual or auditory cues often resolve freezing. Other treatments include behavioural, medical and surgical approaches. If freezing occurs predominantly in the "off" state, increasing the dosage of levodopa may be successful. For "on" freezing, the dose of levodopa may be manipulated – in terms of both dosage and timings - but the response is likely to be less effective and could lead to deterioration so must be expertly handled. Always check with your healthcare professional before altering your medication.
For further information on freezing, tricks to overcome it and treatment approaches see Freezing.
As Parkinson’s progresses
Over time you may notice additional symptoms such as dyskinesia and dystonia but it should be stressed that these do not affect everyone.
Dyskinesia
As the brain produces less and less dopamine over time, it is thought that the remaining cells have to work much harder and the ability of the remaining cells to compensate for the loss of dopamine diminishes. As a result, it is believed that the brain increases its sensitivity to dopamine so that smaller amounts can bring about the same response. This can cause the part of the brain that controls movement to become over-stimulated and excessive and involuntary movement – dyskinesia – result. This situation is exacerbated by levodopa treatment and, as such, the involuntary movements may then subside as levodopa wears off and peak levels of dopamine reduce.
There are various forms of dyskinesia which affect different parts of the body, most commonly the limbs and trunk, and their frequency and timing can differ from person to person.
Dystonia
Another motor symptom that appears in relation to taking levodopa is dystonia: a movement disorder that causes sustained involuntary muscle contractions resulting in abnormal postures and positions. It is thought that, due to reduced dopamine levels, the signals the basal ganglia send to the muscles become irregular. This causes opposing muscles to contract simultaneously and repeatedly over a prolonged period of time, leading to painful, involuntary twisting and problems controlling movement. This can affect just part of or the whole body.
Dystonia is often, but not always, associated with the timing of the levodopa dosage. ‘Off-dystonia’ can occur when the medication is ‘wearing off’. This is particularly common in the morning and many people find that when they wake they have difficulties getting out of bed until the next dose of medication starts to take effect. ‘On-dystonia’ can also occur when levodopa reaches its peak of effectiveness and there is too much dopamine in the brain, as this over-stimulates the muscles and causes spasms.
For further information see Dystonia.
Non-motor symptoms
The term motor fluctuations is widely used when medication starts to be less effective and during this period non-motor symptoms may also be experienced. During wearing off, freezing for example may be experienced together with anxiety, panic attacks, increased heart rate and profuse sweating, but until quite recently non-motor symptoms were given little attention. Far more attention is being focused on these symptoms now, but the term ‘motor fluctuations’ has not altered so far to reflect this.
For further information on non-motor symptoms see Non-Motor symptoms.
