Parkinson Disease
Introduction
Parkinson Disease is a progressive movement disorder characterized by bradykinesia, resting tremor, muscular rigidity and loss of postural reflexes.
- It is due to a loss of dopaminergic neurons in the substantia nigra, as well as other dopaminergic and nondopaminergic areas of the brain.
- The prevalence of Parkinson disease increases with age.
Non-motor complications of Parkinson disease are major causes of disability.
- Fatigue
- Neuropsychiatric symptoms, e.g. depression, anxiety, psychosis
- Sleep disturbances
- Autonomic symptoms, e.g. orthostatic hypotension, bladder dysfunction, constipation, sexual dysfunction
- Pain and other sensory symptoms
- Dysphagia
- Dementia - common in late disease, with a prevalence of 20-40%;
Patients with Parkinson disease are at an increased risk of falls, poor nutrition, weight loss and a loss of muscle mass.
Management
Parkinson disease has no cure, so the principles of treatment are to
- Keep the patient functioning as long as possible with the minimum of medication.
- Choose each patient's therapy according to their disease stage and main symptoms.
Levodopa and non-ergot dopamine agonists are the main drugs used to improve motor function in Parkinson disease.
Nonpharmacological intervention is essential at all stages of Parkinson disease.
- Encourage exercise in all patients.
- Physiotherapy if balance or motor function problems are present.
- Speech and language therapy if they develop communication, swallowing or saliva problems.
- Occupational therapy if they experience difficulties with their daily activities.
- Dietitian referral should be considered.
Consider deep brain stimulation for improving function in patients with motor fluctuation despite optimal medical treatment or for patients with poor tolerability to oral medication.
Medications
Treatment of Parkinson disease is individualised and aimed at reducing movement dysfunction, tremor, postural disability, while managing cognitive changes and minimizing side effects.
For early, symptomatic Parkinson disease, the first-choice options include
- Levodopa
- Metabolic precursor of dopamine.
- Better for improving motor impairment, but is associated with motor complications such as dyskinesias and motor fluctuations.
- Combined in fixed ratio with decarboxylase inhibitor (e.g. carbidopa or benserazide) to prevent peripheral conversion of levodopa to dopamine - allowing a lower dose of levodopa with subsequent decrease in peripheral dopamine adverse effects (e.g. nausea, vomiting, hypotension).
- Non-ergot dopamine agonist (e.g. piribedil, pramipexole, ropinirole, or rotigotine patch)
- As mono- or add-on therapy for many patients
- Have significant side effects such as excessive daytime drowsiness, sleep attacks, nausea and compulsive behaviours.
- Behavioural adverse effects include shopping, eating, hoarding, gambling, sexual preoccupation, medication abuse and punding (incessantly doing and undoing a project [e.g. fixing an engine, organising a wardrobe]).
- Only consider ergot-derived agonist (e.g. cabergoline, bromocriptine) for patients not adequately controlled with non-ergot derived dopamine agonist. Cabergoline and bromocriptine are contraindicated in patients with valve problems or fibrosis in heart, lung or abdomen.
- Monoamine oxidase type B (MAO-B) inhibitor (e.g. selegiline, rasagiline, safinamide)
- May not be as effective for improving motor impairment as other first-line options.
Other medications that can be considered for early symptomatic disease include
- Amantadine
- Has symptomatic benefits and may reduce dyskinesias caused by levodopa or dopamine agonists.
- Some loss of efficacy after 3-6 months.
- Anticholinergic drugs (e.g. benzhexol and benztropine)
- Useful only for tremor.
Managing motor complications
- For patients on levodopa who develop motor fluctuations and increased "off" time, consider adjuvant therapy with dopamine agonists, MAO-B inhibitors, or catechol-O-methyltransferase (COMT) inhibitors such as entacapone to help reduce symptoms.
- Amantadine may be used to reduce dyskinesias.
Apomorphine (intermittent SC injection or continuous infusion with a portable pump)
- Useful in people severely disabled by motor fluctuations refractory to conventional treatment. May allow a reduction in levodopa dosage.
- Is highly emetogenic and requires pre-treatment with domperidone to reduce nausea.
NOTE:
- Avoid all antipsychotics (except quetiapine, clozapine, and pimavnaserin) in older adults with Parkinson disease due to risk of worsening parkinsonian symptoms.
- Pramipexole is associated with improvement in depressive symptoms in patients with Parkinson disease.
- Avoid metoclopramide and prochlorperazine and other centrally acting dopamine-blocking antiemetics in patients with Parkinson disease, because they often make parkinsonism worse.
Dietary Considerations
The absorption of levodopa in the duodenum and its transport across the blood-brain barrier are facilitated by a large neutral amino acid transporter. Ingested protein has the potential to compete with levodopa transport in the gut and brain, thereby reducing levodopa's clinical benefit.
- For patients experiencing motor fluctuations, consider taking levodopa 30-60 minutes before a meal.
- Do not limit protein intake as patients with Parkinson disease are at increased risk for weight loss.
- A protein redistribution diet (PRD), in which most dietary protein intake is reserved for the evening, is sometimes essential, particularly in patients with complex fluctuations such as dose failures and unpredictable "off" periods.
For constipation due to colonic dysmotility, consider increased dietary fiber and fluid intake.
- Polyethylene glycol (macrogol) and probiotics may be considered to treat constipation.
External Links
- DynaMed - Parkinson Disease
- Bromocriptine versus levodopa in early Parkinson's disease, 2007
- Dopamine agonists and the risk of cardiac-valve regurgitation, 2007
- Dopamine agonist therapy in early Parkinson's disease, 2008
- Long-term antidyskinetic efficacy of amantadine in Parkinson's disease, 2010
- Pramipexole for the treatment of depressive symptoms in patients with Parkinson's disease: a randomised, double-blind, placebo-controlled trial, 2010
- Tremor, 2014
- Reports of pathological gambling, hypersexuality, and compulsive shopping associated with dopamine receptor agonist drugs, 2014
- Efficacy of rasagiline and selegiline in Parkinson's disease: a head-to-head 3-year retrospective case-control study, 2017
- International Parkinson and movement disorder society evidence-based medicine review: Update on treatments for the motor symptoms of Parkinson's disease, 2018
- Apomorphine subcutaneous infusion in patients with Parkinson's disease with persistent motor fluctuations (TOLEDO): a multicentre, double-blind, randomised, placebo-controlled trial, 2018
- Safety and efficacy of CVT-301 (levodopa inhalation powder) on motor function during off periods in patients with Parkinson's disease: a randomised, double-blind, placebo-controlled phase 3 trial, 2019
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