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Parkinson's Disease Management

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This article is focused on the management of Parkinson's disease (PD). Further discussion of Parkinson's disease can be found in a related article: Parkinson's Disease and Parkinsonism.

Management

Treatment, as always, should be tailored to the needs of the individual - patients should be helped to make informed decisions about their care, and try and involve the carers as much as the patient will allow.

Parkinson's Disease Management
The Parkinson's Disease Society divides this into 4 stages:¹ Diagnosis - Aims are to communicate information about the disease, help the patient accept the diagnosis, reduce distress and minimise symptoms, and ultimately to improve prognosis. Refer early for assessment to a specialist with an interest in Parkinson's Disease (ideally before any treatment is started). It is important to be sure the diagnosis is correct as misdiagnosis is common - NICE recommends using the UK PDS Brain Bank Criteria for diagnosis²^,³. Arrange nursing assessment. Consider carer support - health and social care assessment. Driving - patient should inform DVLA and insurers. Refer to the Parkinson's Disease Society provides support and information for patients and carers (contact link is at the end of this article). Maintenance - Aims to establish care package, establish lines of communication and build support for the patient, and look out for any complications. Ensure regular access to specialist care - for clinical monitoring and medication adjustments. The diagnosis should be regularly reviewed, particularly if atypical symptoms or signs develop.² NICE suggests specialist review every 6-12 months.² Assess disability and cognition regularly, both by patient self-reporting (e.g. time how long to walk 20 yards; can patient dress alone; can he or she turn over in bed?), and objectively rating motor symptoms (as in the Unified Parkinson's Disease Rating Scale). Don't focus solely on motor symptoms - consider other common problems: sleep disturbance, depression, dementia, and psychosis. Multidisciplinary management is essential. Ideally all patients should have access to: Nurses with a special interest in PD who can monitor clinical condition and adjust medication, as well as providing ongoing support for patient and family and a reliable source of information about all aspects of care. Physiotherapy - to help improve gait, balance and flexibility, improve aerobic activity and movement initiation, increase independence, and provide advice re fall prevention and other safety information. Avoid Zimmer frames (flow of movement is interrupted) unless fitted with wheels and handbrake. Occupational therapy - give advice and help maintaining all aspects relating to activities of daily living, both at work and at home; with the aim of maintaining work and family relationships; encouraging self care where appropriate, assessing any safety issues, making cognitive assessments and arranging any appropriate interventions. Speech and language therapy - improving loudness and intelligibility of speech where possible, ensuring methods of communication are available as disease progresses, and to help with swallowing (reducing risk of aspiration). Consider referral to other services as needed: chiropody/podiatry, continence advisor, psychologist or counsellor, dietician, social services. If patients are hospitalised, every effort should be made to continue the patient's normal routine (especially timing of drug therapy) or catastrophic deterioration of PD may occur. Complex Aims - ongoing patient and carer support, diagnosis and treatment of complications, juggling medications! Aim to optimise quality of life, whilst providing information and support. Good communication between primary and secondary care is essential. Specialist services are likely to be very involved adjusting extremely complex drug regimens. Ensure follow-up plans are clear. Consider apomorphine - in patients with severe motor complication resistant to oral medications. Consider surgery: Bilateral subthalamic nucleus (STN) stimulation in suitable patients who are refractory to medical treatment. Globus pallidus interna (GPi), is also suggested as an alternative by NICE, although this is rarely performed in the UK.² Thalamic stimulation is an alternative for patients with severe tremor who are unsuitable for STN stimulation Palliative Aims - to allow patients to die with dignity in a supportive environment for both patients, family and other carers. Palliative Care requirements - these should be considered and discussed with patients and relatives during all phases of the disease so patients feelings are known.² Referrals may be needed to social services to increase care package. Decide with patient and family whether referral for hospice, nursing home or home palliative care is appropriate. Treat any symptoms (eg pain, anxiety) appropriately, and consider withdrawal or reduction of dopaminergic drugs.

Parkinson's Disease Management

The Parkinson's Disease Society divides this into 4 stages:¹

Diagnosis - Aims are to communicate information about the disease, help the patient accept the diagnosis, reduce distress and minimise symptoms, and ultimately to improve prognosis.
- Refer early for assessment to a specialist with an interest in Parkinson's Disease (ideally before any treatment is started). It is important to be sure the diagnosis is correct as misdiagnosis is common - NICE recommends using the UK PDS Brain Bank Criteria for diagnosis²^,³.
- Arrange nursing assessment.
- Consider carer support - health and social care assessment.
- Driving - patient should inform DVLA and insurers.
- Refer to the Parkinson's Disease Society provides support and information for patients and carers (contact link is at the end of this article).
Maintenance - Aims to establish care package, establish lines of communication and build support for the patient, and look out for any complications.
- Ensure regular access to specialist care - for clinical monitoring and medication adjustments.
- The diagnosis should be regularly reviewed, particularly if atypical symptoms or signs develop.² NICE suggests specialist review every 6-12 months.²
- Assess disability and cognition regularly, both by patient self-reporting (e.g. time how long to walk 20 yards; can patient dress alone; can he or she turn over in bed?), and objectively rating motor symptoms (as in the Unified Parkinson's Disease Rating Scale).
- Don't focus solely on motor symptoms - consider other common problems: sleep disturbance, depression, dementia, and psychosis.
- Multidisciplinary management is essential. Ideally all patients should have access to:
  - Nurses with a special interest in PD who can monitor clinical condition and adjust medication, as well as providing ongoing support for patient and family and a reliable source of information about all aspects of care.
  - Physiotherapy - to help improve gait, balance and flexibility, improve aerobic activity and movement initiation, increase independence, and provide advice re fall prevention and other safety information.
    Avoid Zimmer frames (flow of movement is interrupted) unless fitted with wheels and handbrake.
  - Occupational therapy - give advice and help maintaining all aspects relating to activities of daily living, both at work and at home; with the aim of maintaining work and family relationships; encouraging self care where appropriate, assessing any safety issues, making cognitive assessments and arranging any appropriate interventions.
  - Speech and language therapy - improving loudness and intelligibility of speech where possible, ensuring methods of communication are available as disease progresses, and to help with swallowing (reducing risk of aspiration).
- Consider referral to other services as needed: chiropody/podiatry, continence advisor, psychologist or counsellor, dietician, social services.
- If patients are hospitalised, every effort should be made to continue the patient's normal routine (especially timing of drug therapy) or catastrophic deterioration of PD may occur.
Complex Aims - ongoing patient and carer support, diagnosis and treatment of complications, juggling medications! Aim to optimise quality of life, whilst providing information and support.
- Good communication between primary and secondary care is essential. Specialist services are likely to be very involved adjusting extremely complex drug regimens.
- Ensure follow-up plans are clear.
- Consider apomorphine - in patients with severe motor complication resistant to oral medications.
- Consider surgery:
  - Bilateral subthalamic nucleus (STN) stimulation in suitable patients who are refractory to medical treatment. Globus pallidus interna (GPi), is also suggested as an alternative by NICE, although this is rarely performed in the UK.²
  - Thalamic stimulation is an alternative for patients with severe tremor who are unsuitable for STN stimulation
Palliative Aims - to allow patients to die with dignity in a supportive environment for both patients, family and other carers.
- Palliative Care requirements - these should be considered and discussed with patients and relatives during all phases of the disease so patients feelings are known.²
- Referrals may be needed to social services to increase care package.
- Decide with patient and family whether referral for hospice, nursing home or home palliative care is appropriate.
- Treat any symptoms (eg pain, anxiety) appropriately, and consider withdrawal or reduction of dopaminergic drugs.

Drug treatments

There is no universal first choice drug - this depends on patient's age, clinical symptoms, lifestyle and personal preferences:

Initial drug treatments

Levodopa The most effective drug in the treatment of Parkinson's disease. Virtually all patients respond to it, and treatment is associated with reduced morbidity. Use the lowest effective dose that maintains good function (to avoid subsequent development of dyskinesias etc).²There is no evidence that using modified release L-Dopa initially delays onset of motor complications.²
Dopamine agonists (pramipexole and ropinirole, bromocriptine, cabergoline, lisuride, pergolide). Apomorphine is not used first line and is considered in section on adjuvant therapy.
- They are effective in treating motor features of PD and can be used in early disease. They reduce dyskinesia and motor fluctuations compared with levodopa, but are associated with increased treatment withdrawal and poorer motor scores.
- Acute adverse effects are similar to levodopa and occur at the start of treatment and abate over several days to weeks.
- Traditionally used as an adjunct to levodopa in people who have developed motor complications. There is now evidence to support their use as first-line treatment in place of levodopa. Can be used in young patients (under 50 years) with early disease to reduce the dose of L-dopa required. Are less effective than levodopa, and levodopa is eventually required.
- Prolonged monotherapy (longer than 1 year) is not always successful because of side-effects.
- In people with response fluctuations to levodopa, adjuvant dopamine agonists reduce 'off' time, improve motor impairment and activities of daily living, and reduce levodopa dose, but increase dopaminergic adverse effects and dyskinesias.⁴
- Non-ergot-derived agonists are preferred (pramipexole and ropinirole); the ergot derived drugs (bromocriptine, cabergoline, lisuride and pergolide) need renal function, ESR and CXR before treatment, and repeated annually (see individual drug monographs). Bromocriptine and lisuride are now used less frequently.
Selegiline - (a monoamine-oxidase-B inhibitor).
- Random controlled trials confirmed improvement of symptoms and a delay in the need for levodopa.⁵
- Early research suggesting that Selegiline had a neuroprotective effect has been disproved.⁶^,⁷
- There has also been concern that selegiline may be associated with excess mortality in some people also taking levodopa,⁸but again there is no convincing evidence for this.⁹

Common Management Problems and Complications¹⁰^,¹¹^,¹²^,¹³

Long-term levodopa treatment is associated with adverse motor effects that limit its use. These are motor fluctuations (on-off phenomena, wearing off, dose failures, and freezing) and dyskinesias (peak-dose dyskinesias, diphasic dyskinesia, and dystonia). These become more of a problem as the disease progresses and can be very disabling. They occur in 50-90% of people who have received levodopa for 5-10 years. They occur in virtually all younger patients and so careful consideration needs to be given to the ideal time for starting levodopa in this group. They are less likely to occur in those whose symptoms begin after the age of 70 years. Therefore levodopa should be started immediately in older patients with a limited life expectancy. Dopamine agonist rather than L-dopa is often initiated in younger patients.
"Wearing off" phenomenon - several strategies are available:
- Add in or adjust dose of dopamine agonist.
- Smaller, more frequent doses of L dopa.
- Prolonged release L-dopa preparations (ideally taken at bedtime). Taking both sorts early in the morning may be effective in "jump starting" the system.
- Severe fluctuations may be helped by a liquid carbidopa.
- Adding selegiline or a dopamine agonist may help.
- Dietary adjustments: take L-dopa 30 mins before food.
- COMT inhibitors (eg Entacapone) can be used to prolong the action of l-dopa and increase the "on-time" reduce the levodopa dose, and modestly improve motor impairment and disability¹⁰.
"On Off" fluctuations (patients may switch from severe dyskinesia to immobility in a few minutes):
- Combine levodopa with a dopamine agonist. Cabergoline can be used to reduce levodopa dose and modestly improve motor impairment and disability¹¹.
- Fewer doses of levodopa with intermittent injections or subcutaneous infusion of apomorphine.
- Liquid forms of levodopa (enable more close titration of dose).
- Diet: small snacks and one large evening meal.
Dyskinesias (may occur either at the beginning or end of a dose, or sometimes at its peak):
- At peak dose (usually choreic):
  - Reduce each dose of levodopa but more frequent so that the total daily dose remains the same.
  - Add a long-acting dopamine agonist.
  - Frequent dyskinesias may respond to slow release or liquid L-dopa.
  - Surgery may be indicated.
- At the beginning or end of dose:
  - Try soluble levodopa before meals.
  - Add COMT inhibitor.
Depression and anxiety:
- Depression and anxiety are common in patients with Parkinson's disease. It is very important to detect and differentiate from dementia and to treat. Either tricyclics or SSRIs can be used.
- Use tricyclic antidepressants if the sleep pattern is disturbed. Nortriptyline has the least anticholinergic effects, and so may have least side-effects.
- SSRI's can be helpful if apathy is a predominant feature (but should not be used with selegiline).
- Psychotherapy and support groups are helpful (both for patient and carers).
Hallucinations and psychosis:
- May be related to dopaminergic therapy, disease-related or due to a confusional state (e.g. infection, malnutrition, dehydration or sudden withdrawal of a dopaminergic drug). Consider gradual withdrawal of PD drugs - which may have triggered the psychosis.
- Always consider other causes, it is not always due to Parkinson's disease or drugs.
- Mild symptoms may not need any treatment, but atypical antipsycotics should be used rather than typical ones.
- Clozapine (selective D4 antagonist) may be used on occasions (only by specialists). It reduces hallucinations without aggravating the motor disability of Parkinson's disease.
Dementia: confusion and hallucinations imply a bad prognosis with high mortality within 1-2 years. Management is very difficult and admission to a nursing home is often required.

Adjuvant therapy for more advanced PD

First choice adjuvant drugs in later PD are dopamine agonists, MAO-B inhibitors, or COMT inhibitors.²
Catechol-O-methyltransferase (COMT) inhibitors
- Reversibly inhibit the peripheral breakdown of L-dopa by the COMT enzyme, increasing the amount available for conversion to dopamine in the brain and reducing fluctuations in plasma levels.
- Produce clinical benefits in people with levodopa motor fluctuations and in those with stable responses to levodopa.
- Entacapone should ideally be offered as combination drug (l-dopa carbidopa entacapone) because of poor patient compliance. Tolcapone should only be used if entacapone fails (needs 2 weekly LFT's for first year).²
Antimuscarinic Drugs (orphenadrine, procyclidine, and benzhexol)- evidence for efficacy is poor²:
- May be effective in improving motor function but neuropsychiatric and cognitive adverse events occur frequently and are a more common reason for withdrawal than lack of efficacy.
- May have beneficial effects on tremor in some people. They are useful in reducing sialorrhoea.
- Adverse effects include confusion, hallucinations, and memory impairment (particularly common in the elderly, but may also occur in younger individuals).
- Reduce the symptoms of drug-induced Parkinsonism. They have no beneficial effect on tardive dyskinesia, however, and may make it worse.
Amantadine can be used as monotherapy in early PD (for tremor or bradykinesia) but has a weak and short-lived benefit - and evidence for efficacy is poor.² It can be used as an adjuvant in later PD for reducing dyskinesia, but other drugs are usually considered better.
Apomorphine is given subcutaneously. It can be used as a rescue agent in advanced disease to provide rapid but short-lived benefit for sudden, severe 'off' episodes - use intermittent injections to reduce off time, and continuous infusion to reduce off time and dyskinesias.¹⁴
Modified release l-dopa can also help with symptom control in later stages.

Surgical¹⁵^,¹⁶^,¹⁷

Pallidotomy: indicated for unilateral dyskinesia, severe 'on/off' fluctuations and drug failure .One systematic review found that unilateral pallidotomy improved motor examination and activities of daily living compared with medical treatment, but there is a high incidence of adverse effects. Procedure is only performed on one side as bilateral pallidotomy may cause speech and memory disorders.
Thalamic surgery: effective method of controlling tremor but has no effect on bradykinesia. No randomised trials comparing this with medical treatment.
Subthalamic surgery: can improve tremor, bradykinesia and rigidity but may provoke dyskinesias and hemiballismus.
Deep brain stimulation: electrodes are placed in the basal ganglia and attached to in internal stimulator, which is placed subcutaneously below the clavicle. May be used to provide unilateral or bilateral stimulation. The subthalamus is the preferred target for stimulation. May reverse akinesia, rigidity and tremor. Complications include intracerebral haemorrhage and confusion. NICE have recommended that patients receiving this treatment should be carefully counselled about the risks and benefits, and that it should only be considered after drug treatment has failed.

Document references

Parkinson Aware in Primary Care - leaflet (pdf)
NICE Guidance; #35 - Parkinson's Disease - Diagnosis and Management in Primary and Secondary Care (2006)
Meara J, Bhowmick BK, Hobson P; Accuracy of diagnosis in patients with presumed Parkinson's disease.; Age Ageing. 1999 Mar;28(2):99-102. [abstract]
Unified Parkinson's Disease Rating Scale; MD Virtual University
Tetrud JW, Langston JW; The effect of deprenyl (selegiline) on the natural history of Parkinson's disease.; Science. 1989 Aug 4;245(4917):519-22. [abstract]
Larsen JP, Boas J; The effects of early selegiline therapy on long-term levodopa treatment and parkinsonian disability: an interim analysis of a Norwegian--Danish 5-year study. Norwegian-Danish Study Group.; Mov Disord. 1997 Mar;12(2):175-82. [abstract]
Larsen JP, Boas J, Erdal JE; Does selegiline modify the progression of early Parkinson's disease? Results from a five-year study. The Norwegian-Danish Study Group.; Eur J Neurol. 1999 Sep;6(5):539-47. [abstract]
No authors listed; Selegiline: a second look. Six years later: too risky in Parkinson's disease.; Prescrire Int. 2002 Aug;11(60):108-11. [abstract]
Donnan PT, Steinke DT, Stubbings C, et al; Selegiline and mortality in subjects with Parkinson's disease: a longitudinal community study.; Neurology. 2000 Dec 26;55(12):1785-9. [abstract]
Marsh L, Berk A. Neuropsychiatric Aspects of Parkinson's Disease: Recent Advances Current Psychiatry Reports 2003;5:68-76
Weintraub D, Stern MB; Psychiatric complications in Parkinson disease.; Am J Geriatr Psychiatry. 2005 Oct;13(10):844-51. [abstract]
Depression and Parkinson's - PDS Information Sheet 2006
Molho ES, Factor SA; Parkinson's disease: the treatment of drug-induced hallucinations and psychosis.; Curr Neurol Neurosci Rep. 2001 Jul;1(4):320-8. [abstract]
Gage H, Storey L; Rehabilitation for Parkinson's disease: a systematic review of available evidence.; Clin Rehabil. 2004 Aug;18(5):463-82. [abstract]
Clarke CE, Moore AP; Clinical Evidence - Parkinson's Disease; (subscription required)
Hallett M et al; American Academy of Neurology; Evaluation of surgery for Parkinson's Disease (1999)
Deep Brain Stimulation for Parkinson's Disease; Deep brain stimulation for Parkinson's disease, NICE Interventional Procedure (Nov 2003)

Internet and further reading

Parkinson's Disease Society.

Acknowledgements EMIS is grateful to Dr Huw Thomas for writing this article. The final copy has passed scrutiny by the independent Mentor GP reviewing team. ©EMIS 2009.
Document ID: 469
Document Version: 24
Document Reference: bgp2307
Last Updated: 26 Jun 2007
Planned Review: 25 Jun 2009

The authors and editors of this article are employed to create accurate and up to date content reflecting reliable research evidence, guidance and best clinical practice. They are free from any commercial conflicts of interest. Find out more about updating.

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