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