What are the treatment options for Parkinson's disease (PD) exacerbation?

From the Guidelines

To treat Parkinson's disease exacerbation, advising patients to take levodopa medications at least 30 min before meals and recommending a protein-redistribution dietary regimen can help maximize levodopa absorption and efficacy. This approach is based on the most recent and highest quality study available, which suggests that protein redistribution can improve motor function and disability, and increase the duration of the "ON" state 1.

Key Recommendations

• Advise patients to take levodopa medications at least 30 min before meals to avoid interactions with dietary large neutral amino acids 1
• Recommend a protein-redistribution dietary regimen, with low-protein breakfast and lunch, and consumption of a second course with no quantitative restrictions in terms of protein only at dinner 1
• Monitor patients actively to avoid potential complications, including weight loss, micronutrient deficits, hunger before dinner, and dyskinesias 1
• Consider reducing levodopa doses in patients experiencing the onset or worsening of dyskinesias 1

Rationale

The protein-redistribution dietary regimen is based on the principle that levodopa competes with dietary large neutral amino acids for intestinal absorption and transport across the blood-brain barrier 1. By reducing protein intake at certain times of the day, patients can maximize levodopa absorption and efficacy. This approach has been shown to improve motor function and disability, and increase the duration of the "ON" state, particularly in patients with early stages of Parkinson's disease and those with onset of the disease at a younger age 1.

Important Considerations

• Patients should undergo active monitoring to avoid potential complications associated with protein redistribution, including weight loss, micronutrient deficits, hunger before dinner, and dyskinesias 1
• The role of strict low-protein diet has not been investigated in good-quality clinical trials, and there is no evidence supporting this dietary regimen 1
• Other dietary approaches, such as gluten-free or plant-food-based diets, have not been shown to be effective in managing Parkinson's disease exacerbations 1

From the FDA Drug Label

The primary efficacy endpoint for Study 1 was the change in total daily OFF time assessed from baseline to the end of the 12-week treatment period based on patient diaries. There was a statistically significant reduction in the amount of daily OFF time in patients treated with ONAPGO compared to placebo (p=0.0114; see Table 2). There was also a statistically significant increase in daily ON time without troublesome dyskinesia in patients treated with ONAPGO compared to placebo (p=0. 0188; see Table 3).

Treating Parkinson’s exacerbation with apomorphine (SQ) may be effective in reducing OFF time and increasing ON time without troublesome dyskinesia.

• The study showed a statistically significant reduction in daily OFF time and an increase in daily ON time without troublesome dyskinesia compared to placebo.
• Key benefits of apomorphine (SQ) include:
  • Reduction in OFF time
  • Increase in ON time without troublesome dyskinesia
  • Improvement in Patient Global Impression of Change (PGIC) scores 2

From the Research

Treatment Options for Parkinson's Exacerbation

• Levodopa, a dopamine precursor, is an effective and well-tolerated dopamine replacement agent used to treat Parkinson's disease (PD) 3.
• The combination of levodopa with a dopa-decarboxylase inhibitor (DDCI) and a catechol-O-methyltransferase inhibitor, such as entacapone, can improve the bioavailability of levodopa and reduce motor complications 4, 5.
• Triple combination of levodopa/carbidopa/entacapone available in a single tablet offers flexibility and helps control response fluctuations 3, 6.

Reducing Motor Complications

• Mounting evidence indicates that the short half-life of levodopa and resultant pulsatile stimulation of striatal dopamine receptors leads to wearing off, motor fluctuations, and dyskinesias 4, 7.
• Longer acting dopaminergic agents, such as dopamine agonists, are less likely to cause motor fluctuations and dyskinesias but are not as efficacious for control of motor symptoms 4.
• Continuous delivery of levodopa, such as through duodenal infusion or transdermal patch, may help reduce motor complications 3, 7.

Patient Preference and Quality of Life

• The introduction of levodopa/carbidopa/entacapone in one tablet supported patients' preference for COMT inhibition as an essential component of levodopa/DDCI therapy, reducing the number and size of tablets 5.
• Combined carbidopa/levodopa/entacapone (Stalevo) affords clinical improvements similar to those obtained by separate tablets, with a more positive effect on quality of life 6.