NAA: New Guidelines for Motor Symptoms at Onset of PD Support Levodopa
In some cases, dopamine agonists or MAO-B inhibitors may be warranted
New guidelines for the treatment of motor symptoms in early Parkinson’s disease (PD) have been published by the American Academy of Neurology (AAN), with an emphasis on tremors, stiffness and bradykinesia.
The report, published in Neurology, provides recommendations on the initial treatment of motor symptoms at the onset of PD “to help the clinician and patient choose between treatment options and to guide counseling, prescribing, and monitoring for effectiveness and safety, âwrote lead author of the guideline Tamara Pringsheim, MD, of the University of Calgary in Alberta, Canada, and co-authors.
“Initial treatment with levodopa offers greater motor benefit compared to treatment with dopamine agonists, while levodopa is more likely than dopamine agonists to cause dyskinesia,” they added.
Several treatment strategies reinforce the low dopamine levels seen in PD. Levodopa and dopamine agonists provide precursors for the physiological production of dopamine and synthetic dopamine, respectively. Monoamine oxidase type B (MAO-B) inhibitors such as selegiline, safinamide, and rasagiline, and catechol-O-methyltransferase (COMT) inhibitors such as entacapone, tolcapone, and opicapone increase functionally available dopamine by decreasing dopamine metabolism.
âThere is currently no disease-modifying pharmacological treatment for PD; the current pharmacological treatment of PD is only symptomatic, ânoted Pringsheim and co-authors.
“When symptoms do not cause disability, most people with PD and clinicians are comfortable with a ‘wait and see’ approach, although this requires careful monitoring and patient counseling. not to tolerate a disability or a reduction in the quality of life unnecessarily, âthey observed.
âIn the Parkinson’s Progression Markers Initiative dataset of people with new PD diagnoses who were expected to be able to go without treatment for at least 6 months, 283 of 423 (67%) patients with PD started treatment within 2 years of starting the study, an average of 0.78 (SD 0.5) years after entering the study, âadded the authors of the AAN . âThis gives interested people with de novo PD the opportunity to participate in clinical trials targeting this population. ”
To develop the advice, Pringsheim and colleagues looked at studies of patients with early stage PD (Hoehn and Yahr stages 1 or 2, or within 2 years of disease onset). They assessed the literature on levodopa, dopamine agonists, MAO-B inhibitors, and COMT inhibitors in studies with active comparators only, including 59 articles. They calculated the gross mean difference for motor scores in applicable studies between baseline and study follow-up, as well as the risk differences for changes in hallucination, dyskinesia, arrest due to adverse events and impulse control disorders.
A higher risk of impulse control disorders was associated with dopamine agonists compared to levodopa, reported Pringsheim and co-authors. Long-acting forms of levodopa and levodopa with entacapone did not appear to differ in efficacy from immediate-release levodopa. For dopamine agonists, there was little evidence that different formulations or methods of administration were superior.
The guideline authors incorporated the evidence from the systematic review into the recommendations, assigning each recommendation a level of obligation (A, B, or C). Level A was the highest recommendation level. Level B requirements “are less stringent but still based on the evidence and the benefit-risk profile,” the authors wrote. Level C is the lowest authorized level of recommendation that the AAN considers useful in clinical practice.
Globally. their recommendations included:
Levodopa versus dopaminergic agonist versus MAO-B inhibitors
Clinicians should counsel patients with early PD on the benefits and risks of initial treatment with levodopa, dopamine agonists, and MAO-B inhibitors based on individual disease characteristics (level B). If a treatment is chosen, clinicians should recommend levodopa as the initial preferential dopaminergic therapy (level B).
Clinicians may prescribe dopamine agonists as initial dopamine therapy in patients less than 60 years of age at high risk for dyskinesia (level C), but should not prescribe dopamine agonists in individuals at high risk of drug-related adverse reactions. , including people over 70 years of age, patients with a history of impulse control disorders and patients with pre-existing cognitive impairment, excessive daytime sleepiness or hallucinations (level B).
Immediate rather than controlled-release levodopa or levodopa / carbidopa / entacapone should be prescribed initially, using the lowest effective dose of levodopa and regularly monitoring motor response and dyskinesia, motor fluctuations, disturbances impulse control, excessive daytime sleepiness, postural hypotension. , nausea and hallucinations (level B).
Prescription of dopamine agonists
The patient and caregiver should be informed of side effects, including impulse control disturbances, excessive daytime sleepiness, sudden sleep, nausea, postural hypotension and hallucinations. Patients should be screened for cognitive impairment, excessive daytime sleepiness, sudden onset sleep, hallucinations, orthostatic hypotension, and risk of impulse disorder before prescription and at follow-up (level B).
A positive screening should trigger a targeted clinical interview to determine the extent and severity of symptoms, and the need for clinical management which may include reducing or stopping dopamine agonists. Patient preferences (formulation, mode of administration) and cost should also be taken into account when prescribing a dopamine agonist (level B).
Discontinuation of dopamine agonists
Decrease or stop should be done in the event of debilitating drug-related side effects including impulse control disturbances, excessive daytime sleepiness, sudden sleep, cognitive impairment or hallucinations (level B). Patients should be monitored for withdrawal and, if possible, the dose should be gradually reduced (level B).
Prescribe MAO-B inhibitors
Clinicians should indicate that initial treatment with levodopa has greater motor benefits than MAO-B inhibitors (level B), but may prescribe MAO-B inhibitors as the initial dopaminergic treatment for mild motor symptoms ( level C).
“We have carefully reviewed the available research on the effectiveness and possible risks of drugs for treating motor symptoms in people with early-onset Parkinson’s disease and found that levodopa is generally the best first treatment for these symptoms,” Pringsheim said in an AAN statement.
âHowever, there are side effects with levodopa as well as other medications, 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. her, âshe added.
The new AAN guidelines were approved by the Parkinson Foundation and updated previous practice parameters published in 2002.
New guidelines for the treatment of motor symptoms in early Parkinson’s disease have been published by the American Academy of Neurology, with a focus on tremors, stiffness, and bradykinesia.
The guidelines favor levodopa as the first treatment for motor symptoms, but MAO-B inhibitors or dopamine agonists may be reasonable in some cases.
Paul Smyth, MD, Contributing Writer, BreakingMED â¢
This guideline was developed with the financial support of the AAN. Authors who were AAN sub-committee members or methodologists were reimbursed by the AAN for travel expenses to attend sub-committee meetings.
Pringsheim has received travel funds from the AAN to attend the guidelines subcommittee meetings; is a paid evidence-based medicine consultant for the AAN; received research funding from the MaternalNewbornChild and Youth Clinical Network, the Owerko Center of Alberta Children’s Hospital Research Institute, and the Canadian Institutes of Health Research; and serves as editor for Neurology Clinical Practice.
Cat ID: 37
Subject ID: 82,37,730,37,192,925