Common management problems

Common management problems do occur with medication in PD. Specialist advice should be sought, but common features GPs should know about are; 

Long-term levodopa treatment is associated with adverse motor effects that limit its use. These are motor fluctuations (on-off phenomena, wearing off, dose failures and freezing) and dyskinesias (peak-dose dyskinesias, diphasic dyskinesia and dystonia). They are best managed by a specialist.

'Wearing off' phenomenon

The first few years of levodopa therapy are described as the honeymoon phase because patients with PD enjoy sustained symptomatic relief, however after a number of years (this may be 2-5 years) the levodopa is less effective and  symptoms of Parkinson’s re-emerge between doses- this is described as wearing off. The symptoms of wearing off differ between patients, some may have return of motor symptoms, eg; tremor; rigidity, and others may experience fatigue, sweating, restlessness etc.  A PD diary may be a useful adjunct for doctors / nurses to detect the symptoms of wearing off.

 Several strategies are available

  • Add in or adjust dose of dopamine agonist.
  • Smaller, more frequent doses of levodopa.
  • Prolonged-release levodopa preparations (ideally taken at bedtime). Taking both sorts early in the morning may be effective in 'jump starting' the system.
  • Severe fluctuations may be helped by a liquid carbidopa.
  • Adding selegiline or a dopamine agonist may help.
  • Dietary adjustments: take levodopa 30 minutes before food, to allow medication to start working before the protein in the meal  slows down the amount of levodopa absorbed into the blood stream.
  • COMT inhibitors (eg entacapone) can be used to prolong the action of levodopa and increase the 'on time', reduce the levodopa dose and modestly improve motor impairment and disability.
  • Deep brain stimulation  can help increase the time in the “on state”

'On-off' fluctuations (patients may switch from severe dyskinesia to immobility in a few minutes)

  • Combine levodopa with a dopamine agonist. Cabergoline can be used to reduce the levodopa dose and modestly improve motor impairment and disability.
  • Fewer doses of levodopa with intermittent injections or subcutaneous infusion of apomorphine.
  • Liquid forms of levodopa (enable more close titration of the dose).
  • Diet: small snacks and one large evening meal.

Dyskinesias (may occur either at the beginning or end of a dose, or sometimes at its peak)

  • At peak dose (usually choreic)
    • Reduce each dose of levodopa but make it more frequent so that the total daily dose remains the same.
    • Add a long-acting dopamine agonist.
    • Frequent dyskinesias may respond to slow-release or liquid levodopa.
    • Surgery may be indicated.
  • At the beginning or end of a dose
    • Try soluble levodopa before meals.
    •  Add a COMT inhibitor

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