Treating Parkinson's disease AFTER the honeymoon is over

To reduce "off" time, suggest decreasing the levodopa dosing INTERVAL by 30 to 60 minutes. Don't count on switching to sustained-release levodopa....

As a clinical pharmacist, you will see more emphasis on treating Parkinson's disease AFTER the "honeymoon" is over. For the first few years, symptoms are usually well controlled with low doses of carbidopa/levodopa or a dopamine agonist (pramipexole, etc). But eventually drug efficacy decreases as the disease progresses. Suggest these tips for movement problems with advanced Parkinson's...

"Wearing off" often occurs after about 5 years of levodopa, where its effects start to "wear off" sooner after the last dose. To reduce "off" time, suggest decreasing the levodopa dosing INTERVAL by 30 to 60 minutes. Don't count on switching to sustained-release levodopa (Sinemet CR, etc) to reduce off time, it doesn't help. Next recommend adding a dopamine agonist. This extends "on" time and prevents "deep" offs. Or suggest adding a COMT inhibitor, or an MAO-B inhibitor. For a COMT inhibitor, suggest Comtan (entacapone) or the combo product Stalevo (carbidopa/levodopa/entacapone). Explain that the combo usually costs less than the separate tabs. For an MAO-B inhibitor, suggest selegiline (Jumex) or rasagiline (Dopaminect). Rasagiline has better evidence for reducing off time, but selegiline costs less.

Dyskinesias occur when patients get too much dopamine. Decreasing the levodopa dose may help, but may mean more Parkinson's symptoms, such as tremor, stiffness, and rigidity. If dyskinesias are a problem, suggest decreasing the levodopa dose, and adding a dopamine agonist. These cause fewer dyskinesias than levodopa, and also help decrease Parkinson's symptoms. Or suggest adding amantadine (PK Merz), but watch for CNS side effects. Keep in mind that COMT inhibitors might contribute to dyskinesias. Suggest reducing the dose or stopping the COMT inhibitor if necessary.

References

Pahwa R, Factor SA, Lyons KE, Ondo WG, Gronseth G, Bronte-Stewart H, Hallett M, Miyasaki J, Stevens J, Weiner WJ; Quality Standards Subcommittee of the American Academy of Neurology. Practice Parameter: treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006 Apr 11;66(7):983-95.
Grosset DG, Macphee GJ, Nairn M; Guideline Development Group. Diagnosis and pharmacological management of Parkinson's disease: summary of SIGN guidelines. BMJ. 2010 Jan 12;340:b5614.