What is the treatment for acute exacerbation of Parkinson's disease (PD)?

From the Guidelines

For acute exacerbation of Parkinson's disease symptoms, the primary approach is to optimize antiparkinsonian treatment to ameliorate motor symptoms. This is based on the most recent guideline evidence from the ESPEN guideline on clinical nutrition in neurology 1. The goal is to restore dopaminergic medication levels quickly and address any underlying triggers that may be contributing to the exacerbation.

Key Interventions

• Immediate administration of levodopa is recommended, typically using a dispersible or liquid formulation for faster absorption, with standard dosing being 100-200mg of levodopa (combined with carbidopa) every 2-3 hours as needed.
• For patients who cannot take oral medications, apomorphine can be administered subcutaneously at 2-6mg per dose.
• Adjusting the regular medication regimen by increasing dose frequency or adding a COMT inhibitor like entacapone (200mg with each levodopa dose) may help if the exacerbation is related to medication wearing off.
• Addressing underlying triggers is crucial, including treating any infections, reviewing and discontinuing medications that block dopamine (such as antipsychotics, antiemetics like metoclopramide), ensuring proper hydration, and managing constipation.

Rationale

These interventions work by increasing dopamine availability in the brain, compensating for the depleted dopamine levels that characterize Parkinson's disease and cause motor symptoms like rigidity, bradykinesia, and tremor. Prompt treatment is essential as prolonged exacerbations can lead to complications like aspiration pneumonia or falls, as highlighted in the context of optimizing antiparkinsonian treatment to ameliorate motor symptoms contributing to dysphagia in PD patients 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).

Treating Parkinson’s exacerbation acute with apomorphine (SQ) may be effective in reducing daily OFF time.

• The study showed a statistically significant reduction in daily OFF time in patients treated with ONAPGO compared to placebo.
• The mean change from baseline to week 12 in total daily OFF time was -2.55 hours for ONAPGO and -0.90 hours for placebo.
• The results suggest that apomorphine (SQ) may be a useful treatment option for patients with Parkinson's disease who experience motor fluctuations 2.

From the Research

Treatment Options for Parkinson's Disease Exacerbation

• Levodopa combined with carbidopa is still the most effective treatment for symptoms of Parkinson's disease 3
• Dopamine agonists can be used alone before the introduction of levodopa or as an adjunct to levodopa 3
• Addition of a peripherally-acting COMT inhibitor or an MAO-B inhibitor to levodopa can reduce motor fluctuations in patients with advanced disease 3, 4
• Amantadine may have mild symptomatic benefit and can decrease levodopa-induced dyskinesias 3
• Anticholinergics are rarely used because of their adverse effects, but can be a useful addition to levodopa for control of tremor and drooling 3

Management of Parkinson's Disease in the Acute Hospital Environment

• Maintenance of quality of life through the achievement of steady levels of dopaminergic stimulation within the target neurones of the basal ganglia is the objective for the vast majority of patients 5
• Management of PD medication during intercurrent illness is a challenge, particularly when the gastrointestinal tract is dysfunctional 5
• Problems that may present to the general physician include aspiration pneumonia, uncontrolled dyskinesias, psychosis, dopamine agonist withdrawal syndrome and rarely, neuroleptic malignant-like syndrome 5

Pharmacokinetics and Pharmacodynamics of Levodopa/Carbidopa Cotherapies

• Long-term application of oral levodopa/decarboxylase inhibitor formulations sooner or later supports onset of fluctuations of movement 6
• Inhibition of both, catechol-O-methyltransferase and monoamine oxidase-B supports a more continuous dopamine substitution, which ameliorates fluctuations of motor behavior 6
• This triple combination also enhances both, antioxidative defense and methylation capacity 6