Practice Guideline on Treating Motor Symptoms in Early Parkinson Disease
A Report
of the American Academy of Neurology (AAN) Guideline Subcommittee:
Levodopa preferred as initial dopaminergic therapy for motor symptoms in
patients with early Parkinson disease.
Parkinson
disease (PD) is a neurodegenerative disorder that causes both motor and
nonmotor symptoms and increases in prevalence with age.
Motor symptoms in the early stages of PD include
tremor, rigidity, and bradykinesia, with gait and balance impairment becoming
more prominent with disease progression.
The treatment options for the alleviation of motor
symptoms in the early stages of PD are based on the enhancement of dopaminergic
tone with levodopa, monoamine oxidase inhibitors, dopamine agonists (DAs), or a
combination thereof.
The choice of initial treatment is influenced by the
potential for neuropsychiatric adverse effects associated with DAs and
dyskinesia and motor fluctuations associated with levodopa.
This article is a summary of the
key findings of the practice guideline update.
Recommendation Rationale
·
Initial treatment of early
PD with levodopa provides greater benefit for motor symptoms than initial treatment
with DAs, as shown in the majority of studies that demonstrate greater
improvement in the Unified Parkinson Disease Rating Scale (UPDRS) part III
score for the first 5 years of follow-up.
·
Initial treatment with
levodopa is more likely to induce dyskinesia than initial treatment with DAs
for up to 5 years of follow-up, but the prevalence of severe or disabling
dyskinesia during this 5-year period is low.
· Although initial treatment with DAs is possibly more likely to cause hallucinations than treatment with levodopa, the difference between treatments for this outcome is small for the first 5 years of treatment. Treatment with DAs in early PD is associated with a higher risk of ICDs.
Recommendation Statements
Clinicians should counsel patients with early PD on the benefits and
risks of initial therapy with levodopa, DAs, and MAO-B inhibitors based on the
individual patient's disease characteristics to inform treatment decisions.
In patients with early PD who seek treatment for motor symptoms, clinicians
should recommend levodopa as the initial preferential dopaminergic therapy.
Clinicians may prescribe DAs as the initial dopaminergic therapy to
improve motor symptoms in select early PD patients <60 years who are at
higher risk for the development of dyskinesia.
Clinicians should not prescribe DAs to patients with early-stage PD at
higher risk of medication-related adverse effects, including individuals >70
years, patients with a history of ICDs, and patients with pre-existing cognitive
impairment, excessive daytime sleepiness (EDS), or hallucinations.
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Background and Objectives To review
the current evidence on the options available for initiating dopaminergic
treatment of motor symptoms in early-stage Parkinson disease and provide
recommendations to clinicians.
Methods A
multidisciplinary panel developed practice recommendations, integrating
findings from a systematic review and following an Institute of
Medicine–compliant process to ensure transparency and patient engagement.
Recommendations were supported by structured rationales, integrating evidence
from the systematic review, related evidence, principles of care, and
inferences from evidence.
Results Initial
treatment with levodopa provides superior motor benefit compared to treatment with
dopamine agonists, whereas levodopa is more likely than dopamine agonists to
cause dyskinesia. The comparison of different formulations of dopamine agonists
yielded little evidence that any one formulation or method of administration is
superior. Long-acting forms of levodopa and levodopa with entacapone do not
appear to differ in efficacy from immediate-release levodopa for motor symptoms
in early disease. There is a higher risk of impulse control disorders
associated with the use of dopamine agonists than levodopa.
Recommendations on initial therapy
for motor symptoms are provided to assist the clinician and patient in choosing
between treatment options and to guide counseling, prescribing, and monitoring
of efficacy and safety.
AAN=American Academy of Neurology;
AE=adverse event; CI=confidence interval; COI=conflict of interest;
COMT=catechol-O-methyltransferase; CR=controlled-release; DA=dopamine agonist;
DAWS=dopamine agonist withdrawal syndrome; EDS=excessive daytime sleepiness;
ER=extended-release; ESS=Epworth Sleepiness Scale; GS=Guideline Subcommittee;
ICD=impulse control disorder; IR=immediate-release; MAO-B=monoamine oxidase
type B; MCID=minimal clinically important difference; PD=Parkinson disease;
QUIP=Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease;
SSRI=selective serotonin reuptake inhibitor; UPDRS=Unified Parkinson's Disease
Rating Scale
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