The American Academy of Neurology (AAN) released updated guidelines on the initiation of dopaminergic therapy for the treatment of motor symptoms in patients with early Parkinson disease (PD). A summary of these guidelines was published in Neurology.
During early PD, patients can experience tremor, rigidity, bradykinesia, and gait and balance impairment. The treatment strategy for these symptoms is to enhance the dopaminergic tone by using dopamine agonists (DAs), monoamine oxidase type B (MAO-B) inhibitors, and/or levodopa. There are no current disease-modifying pharmacologic treatment options, and these therapies solely aim at symptom management.
In 2002, the AAN released guidelines about treatment of early PD. Since that time, many new therapeutic options have become available, leading the AAN to release 6 updated recommendations. The neurology group reviewed peer-reviewed studies up until June 2020 that focused on patients with early PD and they also assessed the medications prescribed using the Unified Parkinson’s Disease Rating Scale (UPDRS) part III, which measures motor symptoms.
When prescribing patients with early PD medication for their motor symptoms, physicians must weigh the benefits and risks for each patient individually. Clinical trials have found that levodopa better improved mobility than MAO-B inhibitors or DAs. Compared with MAO-B inhibitors, levodopa was associated with decreased risk for adverse event-related discontinuation and most individuals who used MAO-B inhibitors required additional therapy within 2-3 years. Compared with DAs, levodopa was more likely to cause nonsevere dyskinesia and DAs were more likely to cause hallucinations and impulse control disorders.
Risk for adverse effects from any of these therapies depended on age at disease onset, body weight, gender, and disease severity of the patient. Clinicians should counsel patients about the potential benefits and risks based on their specific characteristics. In general, the AAN recommends for levodopa to be used as the initial preferential dopaminergic therapy. DAs could be considered as the initial treatment among patients who are younger than 60 years of age and are at high risk for dyskinesia.
For the specific regimen of levodopa, physicians must consider that there are multiple formulations such as immediate-release, controlled-release, and extended-release. There was little evidence to support one formulation over another, however, some formulations are associated with increased risk for adverse effects. In general, the committee recommends for immediate-release to be prescribed over controlled-release levodopa or levodopa with carbidopa and entacapone due to the differences in bioavailability and predictability of symptom relief. In order to minimize risk for adverse effects, patients should be given the minimal effective dose.
If a physician feels DAs are the best treatment option, the patient should be made aware of the increased risk for impulse control disorders, hallucinations, excessive daytime sleepiness, sudden-onset sleep, and nausea. Prior to prescribing DAs, patients should be screened for cognitive impairment and risk for impulse control disorders. After prescribing, patients should be assessed for the presence of adverse symptoms using validated questionnaires.
Like levodopa, DAs come in multiple formulations such as short-acting or long-acting and they are also available in various delivery methods, including oral and as transdermal injection. There was little evidence to support the use of a specific
formulation or delivery method over another. The choice of which DA to prescribe should be made on the basis of patient preference and cost. Like levodopa, patients should be prescribed the lowest possible dose to have a therapeutic effect.
If patients on DAs experience adverse effects that necessitate discontinuation, caution must be taken when tapering DAs as many patients experience undesirable effects. During the tapering process, patients should be monitored for symptoms of dopamine agonist withdrawal syndrome and the dosage should be gradually decreased using a staged dosing approach.
If a physician feels MAO-B inhibitors are the best treatment option, patients should be informed that other medications are associated with greater motor symptom improvements and MAO-B inhibitors have a higher risk for adverse event-related discontinuation. The committee advised that MAO-B inhibitors should only be considered among patients with mild motor symptoms.
For the future of early PD, research about nonpharmacologic therapy, such as physiotherapy and exercise should be assessed using controlled research designs. In addition, there is a paucity of data about whether prompt or delayed pharmacologic intervention significantly impacts quality of life and whether there is a genetic component to drug efficacy. Finally, studies should be aimed at finding disease-modifying therapies such that patients are receiving treatment for their PD not just their symptoms.
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Pringsheim T, Day GS, Smith DB, et al. Dopaminergic Therapy for Motor Symptoms in Early Parkinson Disease Practice Guideline Summary: A Report of the AAN Guideline Subcommittee. Neurology. 2021;97(20):942-957. doi:10.1212/WNL.0000000000012868