Treatment of motor symptoms in early-stage Parkinson’s disease: AAN publishes new guidelines

The American Academy of Neurology (AAN) has published updated guidelines for initiating dopaminergic therapy for the management of motor symptoms in patients with early-stage Parkinson’s disease. A summary of these guidelines was published in Neurology.

During early Parkinson’s disease, patients can experience tremors, rigidity, bradykinesia, and gait and balance disorders. The treatment strategy for these symptoms is to increase dopaminergic tone through the use of dopamine agonists (DAs), monoamine oxidase type B (MAO-B) inhibitors, and / or levodopa. There are currently no disease-modifying pharmacological treatment options and these therapies are aimed solely at symptom management.

In 2002, the AAN published guidelines for the treatment of early-stage Parkinson’s disease. Since then, many new therapeutic options have become available, which has resulted in the AAN 6 issuing updated recommendations. Through June 2020, the neurology group reviewed peer-reviewed studies focused on patients with early-stage Parkinson’s disease and also rated prescribed medications using the Unified Parkinson’s Disease Rating Scale (UPDRS), Part III, which measures motor symptoms.

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When prescribing patients on early PD medication for their motor symptoms, physicians must weigh the benefits and risks for each patient individually. Clinical studies have shown that levodopa improves mobility better than MAO-B inhibitors or DAs. Compared to MAO-B inhibitors, levodopa was associated with a reduced risk of discontinuation-related adverse events, and most people taking MAO-B inhibitors needed additional therapy within 2-3 years. Compared to DAs, levodopa was more likely to cause severe dyskinesias, and DAs were more likely to cause hallucinations and impulse control disorders.

The risk of side effects from any of these therapies depended on the patient’s age at onset, body weight, gender and severity of the disease. Physicians should educate patients about the potential benefits and risks based on their specific characteristics. In general, the AAN recommends using levodopa as the first preferred dopaminergic therapy. DAs could be considered as an initial treatment for patients under 60 years of age who are at high risk of dyskinesia.

When making specific levodopa treatment, clinicians must take into account that there are several formulations such as immediate release, controlled release, and extended release. There was little evidence to support one formulation over another, but some formulations are associated with an increased risk of side effects. In general, because of the differences in bioavailability and predictability of symptom relief, the Committee recommends that immediate-release levodopa be prescribed versus controlled-release levodopa or levodopa with carbidopa and entacapone. To minimize the risk of side effects, patients should be given the minimum effective dose.

If a doctor believes DAs are the best treatment option, the patient should be made aware of the increased risk of impulse control disorders, hallucinations, excessive daytime sleepiness, falling asleep suddenly, and nausea. Prior to prescribing DAs, patients should be evaluated for cognitive impairment and the risk of impulse control disorders. Once prescribed, patients should be assessed for adverse effects using validated questionnaires.

Like levodopa, DAs come in several formulations such as short-acting or long-acting, and they are also available in a variety of delivery methods, including oral and transdermal injection. There was little evidence to support the use of any particular one

Formulation or delivery method via another. The choice of DA to prescribe should be based on patient preference and cost. Like levodopa, patients should be prescribed the lowest possible dose for therapeutic effect.

If patients on DA develop side effects that require discontinuation, caution should be exercised in tapering the DA as many patients experience side effects. During the taper, patients should be monitored for symptoms of dopamine agonist withdrawal syndrome and the dosage should be reduced gradually using a gradual dosing approach.

If a doctor believes that MAO-B inhibitors are the best treatment option, patients should be informed that other drugs are associated with greater improvement in motor symptoms and that MAO-B inhibitors have a higher risk of discontinuation Related to adverse events. The committee noted that MAO-B inhibitors should only be considered in patients with mild motor symptoms.

For the future of early Parkinson’s disease, research on non-pharmacological therapies such as physical therapy and exercise should be assessed using controlled research designs. In addition, there is little data on whether immediate or delayed pharmacological intervention significantly affects quality of life and whether the effectiveness of drugs has a genetic component. Finally, studies should aim to find disease-modifying therapies so that patients receive treatment for Parkinson’s disease not just for their symptoms.

Disclosure: Several authors stated links to industry. For a full list of the details, see the original article.

reference

Pringsheim T., Day GS, Smith DB, et al. Dopaminergic Therapy for Motor Symptoms in Early Parkinson’s Practice Guideline Summary: A Report by the AAN Guidelines Subcommittee. Neurology. 2021; 97 (20): 942-957. doi: 10.1212 / WNL.0000000000012868