Neurologists should counsel people with early Parkinson's disease about the benefits and risks of starting treatment with levodopa, dopamine agonists, or monoamine oxidase B (MAO-B) inhibitors for motor symptoms, new guidelines from the American Academy of Neurology (AAN) stated.
If treatment is started, levodopa is the preferred initial therapy for most early Parkinson's patients, wrote Tamara Pringsheim, MD, of the University of Calgary in Alberta, Canada, and co-authors in .
"We carefully reviewed the available research on the effectiveness and possible risks of medications to treat motor symptoms in people with early Parkinson's disease and found that levodopa is usually the best first treatment for these symptoms," Pringsheim said in an AAN statement.
"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," she added.
The guidelines update AAN practice parameters from 2002. Since then, new medications and new formulations of older medications have become available, Pringsheim and colleagues noted.
To create the new recommendations, the guideline authors reviewed peer-reviewed articles through June 2020 of people with early stages of Parkinson's. The team evaluated studies that assessed dopamine agonists, levodopa, MAO-B inhibitors, and catechol-O-methyltransferase against active comparators, using the Unified Parkinson's Disease Rating Scale () part III as the preferred motor symptom measure.
The analysis showed:
- Levodopa was better at reducing motor symptoms than dopamine agonists, with most studies demonstrating significantly greater improvement in UPDRS part III scores for up to 5 years of follow-up
- Levodopa also was more likely to cause dyskinesia during the first 5 years of treatment than dopamine agonists, but prevalence of severe or disabling dyskinesia in this timeframe was low
- Dopamine agonists were more likely to cause hallucinations or impulse-control disorders like compulsive gambling, eating, shopping, or sexual activity, and were associated with a higher risk of excessive daytime sleepiness
- Patients on dopamine agonists and MAO-B inhibitors were more likely to stop treatment due to side effects than those taking levodopa
- No single formulation of dopamine agonists seemed superior to others, and long-acting forms of levodopa did not seem to differ in efficacy from immediate-release levodopa
The literature review provided inadequate data about the effect of levodopa versus MAO-B inhibitors on early motor symptoms, the guideline authors said.
"Clinicians should initially prescribe immediate-release levodopa rather than controlled-release levodopa or levodopa/carbidopa/entacapone in patients with early Parkinson's disease," Pringsheim and co-authors recommended. The lowest effective dose should be prescribed and neurologists should counsel patients that higher dosages are more likely to cause dyskinesia.
"Clinicians may prescribe dopamine agonists as the initial dopaminergic therapy to improve motor symptoms in select early Parkinson's disease patients under 60 years who are at higher risk for the development of dyskinesia," the guideline authors added.
"Clinicians should not prescribe dopamine agonists to patients with early-stage Parkinson's disease at higher risk of medication-related adverse effects, including individuals over 70 years, patients with a history of impulse control disorders, and patients with pre-existing cognitive impairment, excessive daytime sleepiness, or hallucinations," the authors continued.
Patients may not recognize or report side effects associated with dopamine agonists, the guideline writers cautioned. "Systematic and specific interrogation by practitioners concerning impulsive behaviors, sleep-related behaviors, and perceptual disturbances may set expectations and normalize reporting of embarrassing behaviors, leading to improved recognition of problematic adverse effects associated with dopamine agonist use."
The guideline also addressed screening patients for risk factors for adverse effects, tapering and discontinuing dopamine agonists, the role of MAO-B inhibitors in early Parkinson's, and suggestions for future research.
"Choosing to start a medication is a collaborative decision between a person with Parkinson's disease, their neurologist, and their caregiver," Pringsheim noted. "The right medication will depend on a person's symptoms, age, and life circumstances."
Disclosures
This guideline was developed with financial support from the AAN.
Pringsheim received travel funding from the AAN to attend Guideline Subcommittee meetings, is a paid evidence-based medicine consultant for the AAN, received research funding from the Maternal Newborn Child and Youth Strategic Clinical Network, the Owerko Center of Alberta Children's Hospital Research Institute, and the Canadian Institutes of Health Research, and serves as an editor for Neurology Clinical Practice. Co-authors reported numerous relationships with academic institutions, non-profit entities, publishers, and industry. None had conflicts of interest significant enough to preclude them from authorship, according to the AAN.
Primary Source
Neurology
Pringsheim T, et al "Dopaminergic therapy for motor symptoms in early Parkinson disease practice guideline summary: A report of the AAN Guideline Subcommittee" Neurology 2021; DOI: 10.1212/WNL.0000000000012868.