Understanding Parkinson's Disease

Pharmacological treatment options for Parkinson's disease

The Treatment Decision Pathway¹

Dopamine replacement therapy with levodopa has been the mainstay of symptomatic treatment of Parkinson's disease (PD) for almost 40 years. However, several additional dopaminergic drugs have been introduced over the years to provide alternatives for patients with PD. Practical challenges in the management of PD include:

• Determining the point at which drug therapy should be initiated and with what treatment
• The sequence and combination of drugs required as the disease progresses
• The place for parenteral therapy and surgery in advanced PD¹

Dopaminergic drugs e.g. levodopa, dopamine agonists and the MAO-B inhibitors are the principal therapeutic options for the motor symptoms of PD and all have appropriate supporting clinical data.¹ There are some important considerations in the use of these treatments and in designing the best long-term strategy for a patient with PD (Figure 1):

• Effective symptom control
• Delaying motor complications such as dyskinesias
• Individual patient characteristics¹

As PD progresses, the provision of effective symptom control becomes more challenging and additional drugs may need to be added. For example, for those who initially received an MAO-B inhibitor, the introduction of a dopamine agonist is the logical next step. Those already receiving a maximally effective or tolerated dose of an agonist and who require additional treatment may benefit from a MAO-B inhibitor. For most of these patients, levodopa is the subsequent choice (Figure 2).

The emergence of motor fluctuations complicates drug use and scheduling. Wearing off is often under-diagnosed and its treatment can significantly improve the motor control of the patient with PD. For those already receiving levodopa who require better symptom control, the total daily dose may be raised by increasing each individual dose and / or dosage frequency. However, this may lead to a greater risk of dyskinesias. The addition of a catechol-O-methyltransferase (COMT) inhibitor will decrease the gastrointestinal breakdown of levodopa, increase its half life, reduce "off" time, and increase "on" time and therefore is an effective treatment for wearing off (Figure 2).¹

As the disease becomes more advanced, the neuronal degeneration continues and motor complications emerge, which inevitably leads to more complex treatment regimens
(Figure 3).

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