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The Need for Enhanced Strategies to Manage Levodopa-Induced Dyskinesia in Parkinson’s Disease

The Need for Enhanced Strategies to Manage Levodopa-Induced Dyskinesia in Parkinson’s Disease

Levodopa in the Treatment of Parkinson’s Disease (PD)
PD affects an estimated 1 million people in the United States, with approximately 60,000 people newly diagnosed each year.1 The prevalence increases with age, and because of the growing aging population, the number of patients with PD is expected to double by 2030.2

Neurodegenerative features of PD include the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies in the residual dopaminergic neurons.3,4 Although pathologic changes can be detected up to 20 years before the onset of motor symptoms and other early nonspecific symptoms (Figure 1A),5 most patients are diagnosed only when symptoms appear in their 50s and 60s.6

The overall clinical course of PD and the spectrum of signs and symptoms can vary considerably among patients.7,8 Because interventions that cure PD or at least modify its progression are not currently available, treatment for patients with PD focuses on improving functional disability due to motor and nonmotor symptomology, which generally requires lifelong pharmacologic therapy.9 Surgical options, such as deep brain stimulation, are also available for symptomatic control, but tend to be reserved for patients with advanced disease in whom disabling symptoms progress despite optimal medical therapy.4

The primary aim of pharmacologic treatment is to restore striatal dopamine activity to the fullest extent possible. To this end, levodopa, the precursor of dopamine, has been the mainstay option for improving PD symptoms since becoming available in the 1960s. Despite the subsequent development and availability of other agents such as dopamine agonists, monoamine oxidase B inhibitors, catechol-O-methyltransferase (COMT) inhibitors, and N-methyl D-aspartate (NMDA) receptor inhibitors, levodopa remains the gold standard for treating parkinsonian symptoms, especially bradykinesia or rigidity (Figure 1B).4,9

Levodopa improves disability and capacity to perform important activities of daily living (ADL). Approximately 85% of patients have some degree of benefit with this therapy.10 Although treatment with levodopa effectively reduces parkinsonian symptoms, it has also been associated with numerous adverse events.10 The most common and burdensome adverse events associated with long-term levodopa use are abnormal involuntary movements (dyskinesias), typically referred to as levodopa-induced dyskinesia (LID).4

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