"OFF" Times - Motor Fluctuations

As Parkinson's disease progresses, it is common for more dopamine - producing brain cells to die causing the benefits from Parkinson's medication to not last as long as they did before. The brain eventually reaches a point where it stops producing dopamine in large amounts and therefore must rely on medicine to replace dopamine. Researchers think this happens for two reasons.

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• As Parkinson's progresses, cells become less able to store dopamine. When this occurs, the cells are unable to release dopamine without medications, such as levodopa. When the dose fades, 60-90 minutes after taking it, there is no more levodopa for the cells to use, resulting in lower dopamine levels and a worsening of symptoms (off times).

• The cells in your brain become more sensitive to both higher and lower concentration of levodopa. There is a higher likelihood of experiencing "off times" when levodopa levels are too low and a higher likelihood of experiencing dyskinesis (involuntary movements) when levodopa levels are too high.

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As a result, your doctor may advise you to increase your medication doses to achieve optimal control of motor symptoms, such as tremor, slowness and rigidity. The goal is to maximize symptom control without increasing side effects.

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Non-motor Fluctuations

Many non-motor symptoms can also be affected by "off" time. Non-motor symptoms are Parkinson's symptoms that are not related to movement, such as mood, cognition, or fatigue. Mood fluctuations are particularly common and are often experienced as a general state of dissatisfaction with life, irritability, depression, or anxiety. If you notice a relationship between mood changes and the timing of your PD medication, tell your neurologist. He or she might be able to adjust your dopamine replacement medications or dose to reduce "off" time, which may help your mood. Many people experience anxiety as their anti-Parkinson's medications wear off, near the end of the dosing cycle. If you or someone close to you notices a pattern of anxiety associated with "on-off" fluctuations, talk to your neurologist about adjusting your medications. Psychotherapy can also be helpful in this situation. If there is a pattern of "off" state anxiety, a therapist can help you learn to anticipate the anxiety and cope with it through relaxation techniques and other cognitive behavioral strategies.

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Treating "On-Off" Fluctuations

The goal of managing motor fluctuations and dyskinesias is to help you remain as active and independent as possible. Depending on your current medications there are several approaches your doctor can take to help smoothen your response to medications to minimize or avoid fluctuations. Your doctor may:

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• Adjust the dose of levodopa, either by increasing the dose or frequency

• Add different medications to your current regimen to help keep levels of dopamine more consistent to avoid "off" time. Examples are COMT-inhibitors, dopamine agonists, or MAO-B inhibitors.

• Try a controlled-release or extended-release formulation or carbidopa-levodopa, designed to extend the benefits from the same dose of carbidopa-levodopa and possibly decrease the number of pills needed per day.

• Bring up surgical options, like deep brain stimulation or Doupa therapy.

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Other Common Issues

In addition to a return of PD symptoms and onset of dyskinesia, some people experience dystonia and/or freezing with motor fluctuations. Dystonia is when muscles continuously contract, causing parts of the body to twist or curl. Dystonia may occur at peak dose when the medication is working at its best. More commonly, dystonia occurs when dopamine levels are the lowest ("off" periods) or when medications are just starting to kick in.

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"Freezing" is the temporary and involuntary inability to move. If freezing happens when the next dose of medication is due, it is called "off" freezing.

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Medication Management of Motor Fluctuations

Usually, freezing episodes decrease after taking medications. Different medications are available to treat "off" episodes. (You can read more about each of these in detail under Medications on this site). They include:

• Levodopa

• Dopamine Agonists

• Amantadine

• Adenosine A2a Antagonists

• COMT Inhibitors

• MAO-B Inhibitors

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