What are the strategies for treatment escalation in Parkinson's disease (PD)?

From the Guidelines

Treatment escalation in Parkinson's disease should prioritize a protein-redistribution dietary regimen to maximize levodopa absorption and efficacy, in addition to traditional pharmacological interventions. This approach is supported by the ESPEN guideline on clinical nutrition in neurology 1, which recommends advising patients experiencing motor fluctuations to try complying with a protein-redistribution dietary regimen. The guideline suggests redistributing protein intake throughout the day, with a low-protein breakfast and lunch, and consuming a second course with no quantitative restrictions in terms of protein only at dinner. This regimen has been shown to improve motor function and disability, and increase the duration of the "ON" state, particularly when proposed to patients in the early stages of Parkinson's disease and with onset of the disease in younger age.

When considering pharmacological interventions, levodopa remains the gold standard for motor symptom control, often combined with carbidopa to reduce peripheral side effects. Dopamine agonists like pramipexole or ropinirole can be added when levodopa efficacy wanes or motor fluctuations develop. For patients experiencing "wearing off" phenomena, COMT inhibitors such as entacapone or MAO-B inhibitors like rasagiline can extend levodopa's duration of action. Advanced disease may require continuous dopaminergic stimulation through rotigotine patches, apomorphine pumps, or levodopa-carbidopa intestinal gel. However, these interventions should be considered in conjunction with the protein-redistribution dietary regimen, as recommended by the ESPEN guideline 1.

Key considerations in treatment escalation decisions include:

• Patient's age, cognitive status, and comorbidities
• Regular monitoring for motor complications, non-motor symptoms, and medication side effects
• Potential benefits and risks of each intervention, including protein-redistribution dietary regimens and pharmacological interventions
• Importance of weight management and nutritional assessment, as highlighted in the ESPEN guideline on clinical nutrition in neurology 1

Overall, a comprehensive approach to treatment escalation in Parkinson's disease should prioritize both pharmacological and non-pharmacological interventions, including protein-redistribution dietary regimens, to optimize patient outcomes and improve quality of life.

From the FDA Drug Label

The effectiveness of pramipexole dihydrochloride tablets in the treatment of Parkinson's disease was evaluated in a multinational drug development program consisting of seven randomized, controlled trials Three were conducted in patients with early Parkinson's disease who were not receiving concomitant levodopa, and four were conducted in patients with advanced Parkinson's disease who were receiving concomitant levodopa In all studies, the Unified Parkinson's Disease Rating Scale (UPDRS), or one or more of its subparts, served as the primary outcome assessment measure

Treatment Escalation in Parkinson's Disease:

• The drug label provides information on the effectiveness of pramipexole in patients with early and advanced Parkinson's disease.
• In patients with early Parkinson's disease, pramipexole was shown to be effective in improving UPDRS part II (ADL) and part III (motor performance) scores.
• In patients with advanced Parkinson's disease, pramipexole was also effective in improving UPDRS scores and reducing "on" and "off" time.
• The studies demonstrated a statistically significant difference in favor of pramipexole compared to placebo, with improvements seen as early as week 2-3 of treatment.
• However, the label does not provide specific guidance on treatment escalation in Parkinson's disease, such as when to increase the dose or switch to a different medication.
• Therefore, treatment escalation decisions should be made on a case-by-case basis, taking into account individual patient response and tolerability to pramipexole 2.

From the Research

Treatment Escalation in Parkinson's Disease

• Treatment escalation in Parkinson's disease is a complex process that involves the management of motor and non-motor symptoms, as well as the mitigation of treatment-related complications 3, 4.
• As the disease progresses, patients may experience worsening symptoms, functional impairment, and decreased quality of life, necessitating the use of advanced treatments such as deep brain stimulation, levodopa-carbidopa enteral suspension, and continuous subcutaneous apomorphine infusion 4, 5.
• Dopamine agonists and monoamine oxidase type-B inhibitors are effective treatments for Parkinson's disease, both as monotherapy and in combination with levodopa, with selegiline being the best option in combination with levodopa among the investigated drugs 6.
• The choice of treatment is influenced by scientific evidence, clinical expertise, and patient preferences, and patients should be engaged in the decision-making process to ensure that their needs and preferences are taken into account 5.

Advanced Treatment Options

• Deep brain stimulation, levodopa-carbidopa intestinal gel, and continuous subcutaneous apomorphine infusion are advanced treatment options for patients with advanced Parkinson's disease, and the choice of treatment depends on the individual patient's needs and circumstances 7, 5.
• These treatments can improve quality of life, activities of daily living, and motor symptoms, but may also be associated with adverse events, and patients should be informed about the potential benefits and risks of each treatment option 5.
• The evidence for these treatments should be presented in a way that is comprehensible and comparable, to facilitate informed decision-making by patients and clinicians 5.

Management of Motor and Non-Motor Symptoms

• The management of motor and non-motor symptoms in Parkinson's disease requires a comprehensive approach that includes pharmacologic and non-pharmacologic interventions, as well as rehabilitative therapy and exercise 3, 7.
• Dopamine-based therapies are effective for initial motor symptoms, but non-motor symptoms require nondopaminergic approaches, such as selective serotonin reuptake inhibitors for psychiatric symptoms and cholinesterase inhibitors for cognition 3.
• Palliative care is an important aspect of Parkinson's disease management, and patients should have access to supportive care and symptom management throughout the course of their illness 3.