Wearing off

There is insufficient evidence to conclude that any one drug is superior to another in reducing off-time. The following strategies may be used, either alone or in combination:

• Adjustment of levodopa dosing:
• This may be useful during early disease when motor fluctuations are just becoming apparent.
• Usually an increase from three to six smaller daily doses (whilst maintaining the total daily dosage) is used.
• Oral adjuvant therapy:
• Oral catechol-O-methyl transferase inhibitors (COMT) inhibitors and monoamine oxidase-B inhibitors:
• Reduce off-time by 1–1.5 hours per day.
• Are likely to be equivalent in effectiveness.
• Oral dopamine agonists:
• Reduce off-time.
• There is no evidence to guide choice of dopamine agonist, but ergot agonists are not recommended first-line because of the risks of fibrotic reactions.
• Amantadine may be used if other strategies fail.
• Other strategies:
• Deep brain stimulation (DBS) of the subthalamic nucleus (STN).
• Subcutaneous apomorphine.
• Switch from standard to modified-release levodopa (but this can lead to an increase in off-time).
• Switch from standard to modified-release or transdermal dopamine agonist.
• Oral dispersible levodopa (co-beneldopa).
• Levodopa gel via jejunostomy.

On-off phenomenon

There is insufficient evidence for any specific strategies or treatments for the on-off phenomenon, although the strategies for wearing off and dyskinesia may be considered.

[Horstink et al, 2006; National Collaborating Centre for Chronic Conditions, 2006; Pahwa et al, 2006]