Parkinson’s disease: Management
· Remember to advise patients to inform the DVLA and their insurance companies of a diagnosis of Parkinson’ disease
A summary of medications used in Parkinson’s disease
Type of drug
Notes
Levodopa and decarboxylase inhibitor ie Madopar (co-beneldopa),Sinemet (co-careldopa)
Amino acid precursor of dopamine; absorbed in the jejunum
Side effects: nausea and vomiting, postural hypotension, drowsiness, hallucinations/nightmares/psychosis at high dosages
Main treatment in older patients
Best at treating motor symptoms
Dopamine agonists: Ropinerole, Pramipexole, Rotigotine (Non ergot)
Ergot derivatives are not advised as risk of fibrotic reactions
Side effects: Confusion, hallucinations, nausea, postural hypotension, somnolence, pathological gambling, hypersexuality
Main treatment in younger patients
Avoided in older patients as risk of neuropsychiatric complications
Monoamine oxidase inhibitors eg Selegiline, rasagiline
Prevents central breakdown of L-dopa
Increased mortality in mild PD when combined with L-dopa therefore used alone or in late disease
COMT inhibitor: Entacapone
Prevents peripheral breakdown of L-dopa
Side effect: orange urine
Amantadine
Glutamate antagonist
Reduces dyskinesia
Apomorphine (parenteral treatment)
Used in advanced disease
· No treatment has been shown to delay disease progression
Initial drug management
Usually initiated once symptoms affect ability to function
Levodopa
· Older patients with or without cognitive impairment
· Most effective at treating motor symptoms
· Risk of motor complications as Parkinson’s disease progresses
· Low maintenance dose reduces development of dyskinesia
· Prolonged use associated with weight loss
· Associated with reduced morbidity
· Modified release levodopa may be used in later stages of the disease
Dopamine agonists
· Pramipexole, ropinerole (Non ergot orals) Rotigotine patch
· Most appropriate for younger patients without dementia
· Early treatment can reduce the risk of developing dyskinesias and reduces fluctuations compared to levodopa
· If side effects, replace with alternative dopamine agonist or use another drug type
· Avoid ergot derivative drugs; if used will need to monitor renal function, ESR and CXR annually
· Addition of levodopa will eventually be required (approximately after a year)
· Adjuvant dopamine agonists to levodopa reduce ‘off’ episodes and improve motor function
MAO-B inhibitors (Selegiline, Rasagiline)
· Used in mild disease; can be used as monotherapy or early adjuvant therapy
· Prevents the breakdown of the dopamine in the brain, by blocking monoamine oxidase type B (MAO-B)
· Rasagiline was thought to have a neurodegenerative effect (5), but subsequent studies have failed to support this hypothesis
· Used to make levodopa last longer or reduce the amount required
· May worsen dyskinesias, hallucinations or vivid dreaming
COMT-Inhibitors: Stalevo triple (levodopa, carbidopa and entacapone) ; Entacapone
· Inhibits peripheral breakdown of dopamine
· Reduce motor flucatuations
· When used combined with levodopa, COMT inhibitors can reduce the daily ‘off’ time and increase the ‘on’ time
· The dose and frequency of levodopa can be reduced
· Side effects: dyskinesia, nausea, vomiting and diarrhoea
Later drug treatment
· Used as complications of earlier treatments develop and symptoms become more severe
· Adjuvant treatments in later stage Parkinson’s disease include dopamine agonists, MAO-B inhibitors and COMT inhibitors
· Progression to advanced disease includes unpredictable episodes of wearing off, freezing and dysphagia
Amantadine
· Reduces dyskinesias when used as an adjuvant
· Has a weak and short term effect
Apomorphine
· Useful if patient has dysphagia during severe ‘off’ episodes
· Intermittent subcutaneous injections may reduce the off time in patients with severe motor complications. Can be used acutely for severe off episodes
· Continuous subcutaneous infusions may be used to reduce off time and dyskinesia in patients with severe motor complications
Surgery
· Subthalamus deep brain stimulation (6) can be used if motor fluctuations and dyskinesis fail to respond to the above strategies
Bilateral subthalamic nucleus (STN) or globus pallidus interna (GPi) stimulation may be used for people with PD who:
- Have motor complications that are refractory to best medical treatment
· Are biologically fit with no clinically significant active comorbidity
· Are levodopa responsive and
· Have no clinically significant mental illness such as depression or dementia
Other therapies
Physiotherapy
· Exercise, especially progressive resistance actvities, improves motor function
Focus on:
· Gait re-education
· Balance and flexibility
· Improve aerobic capacity
· Improve movement initiation
Speech and language therapy
· Improve vocal volume and pitch range, including speech therapy programmes such as Lee Silverman Voice treatment
· Teaching strategies to optimise speech intelligibility
· Ensuring an effective means of communication is maintained throughout the course of the disease, including use of assistive technologies
· Review safety and efficiency of swallowing and to minimise the risk of aspiration
Palliative care
· Ultimately the majority of patients fail to respond to further dopaminergic therapy and symptoms continue to deteriorate
· The aim of treatment then becomes supportive
· Discuss end of life care sooner rather than later
· Dyskinesia is more comfortable than dystonic state