The guideline updates previous recommendations for dopaminergic medications published in 2002, integrating new medications and formulations.
The American Academy of Neurology (AAN) has issued a new clinical practice guideline with recommendations for treatment of motor symptoms in early Parkinson disease (PD) this week. This new guidance updates an existing practice guideline published in 2002 that outlines initiation of treatment for early PD and use of dopaminergic medications.1,2
The panel of authors assigned 3 levels of obligation for recommendations—A, B, and C—using the Delphi process. Level A represents the strongest recommendations, which use the word “must” due to high confidence in evidence that suggest high benefit and low risk for patients. There were no Level A recommendations made within the guideline. Level B recommendations encompass what clinicians “should” do; while they are not as strong as Level A recommendations, they are still based on a similar benefit-risk profile (FIGURE). Level C represents the lowest recommendations, with practices clinicians “may” want to consider.2
“We carefully reviewed the available research on the effectiveness and possible risks of medications to treat motor symptoms in people with early Parkinson disease and found that levodopa is usually the best first treatment for these symptoms,” lead guideline author Tamara Pringsheim, MD, MSc, professor of neurology, department of clinical neurosciences, psychiatry, pediatrics and community health science, the University of Calgary in Alberta, Canada; and a Fellow of the AAN, said in a statement.1 “Still, there are side effects with levodopa as well as other drugs, so it is important that a person newly diagnosed with Parkinson's disease discusses all options with their neurologist before deciding on the best treatment plan for them.”
Recommendations assist clinicians and patients when choosing initial pharmacologic treatment for motor symptoms, comparing levodopa, dopamine agonists (DAs), and monoamine oxidase type B (MAO-B) inhibitors. Treatment with levodopa was found to provide superior benefit to dopamine agonists and MAO-B inhibitors in improving motor symptoms and was recommended as the preferential treatment for patients seeking this variety of treatment (Level B).
Levodopa was also more likely than dopamine agonists to cause dyskinesia for up to 5 years of follow-up, leading panel authors to recommend prescribing DAs as the initial therapy for patients with early PD who are less that 60 years and at a higher risk for dyskinesia (Level C). Comparably, DAs were not recommended to be prescribed to patients at a higher risk for medication-related adverse events (AEs), particularly patients older than 70 years, those with a history of impulse control disorders, or those with cognitive impairment, excessive daytime sleepiness, or hallucinations (Level B).
In treating motor symptoms early on in PD, immediate release (IR) levodopa was not found to be more or less effective than levodopa with entacapone or long-acting forms of the drug. Recommendations include prescribing IR levodopa initially, prescribing the lowest effective dose to minimize risk of dyskinesia and other adverse events (AEs), and continually counseling patients on potential treatment effects and risks, and monitoring for treatment response (all Level B).
A higher risk of impulse control was associated with use of dopamine agonists when compared with levodopa. Recommendations for prescription of DAs included informing patients of side effects; preemptively screening for cognitive impairment, impulse control disorders hallucinations, and other conditions, while including the caregivers in the process; and screening for AEs related to DA treatment (all Level B). Also recommended were incorporating patient preferences, prescribing the lowest dose of DA to provide therapeutic benefit, tapering or discontinuing treatment in the event of treatment-related AEs, and monitoring for dopamine agonist withdrawal symptoms if discontinued. When investigating different formulations of DAs, evidence was limited in determining whether an individual formulation or method of administration was preferred.
When prescribing MAO-B inhibitors, panel authors recommended counseling patients on the greater motor benefits associated with levodopa treatment (Level B), but also stated clinicians may prescribe MAO-B inhibitors initially for patients with mild motor symptoms (Level C). Practice recommendations were developed following a systematic review, which was compliant with the Institute of Medicine processes for transparency and patient engagement.
“Choosing to start a medication is a collaborative decision between a person with Parkinson's disease, their neurologist, and their caregiver,” Pringsheim added in the statement.1 “The right medication will depend on a person's symptoms, age and life circumstances. They are encouraged to discuss the potential benefits and adverse effects of medication options with their neurologist and care team.”
Future research efforts are necessitated to investigate whether quality of life is affected by early treatment of symptoms or if the “wait and watch” strategy is preferred. Influence of genetic status on therapy initiation should be evaluated, while also incorporating more personalized approaches to medicine and treatment in PD.