1 Guidance

1.1 Communication with people with Parkinson's disease and their carers

1.1.1 Communication

1.1.1.1 Communication with people with PD should be aimed towards empowering them to participate in the judgements and choices about their own care.

1.1.1.2 Discussions should be aimed at achieving a balance between the provision of honest realistic information about the condition and the promotion of a feeling of optimism.

1.1.1.3 Because people with PD may develop impaired cognitive ability, a communication deficit and/or depression, they should be provided with:

  • both oral and written communication throughout the course of the disease, which should be individually tailored and reinforced as necessary

  • consistent communication from the professionals involved.

1.1.1.4 Families and carers should be given information about the condition, their entitlements to care assessment and the support services available.

1.1.1.5 People with PD should have a comprehensive care plan agreed between the individual, their family and/or carers and specialist and secondary healthcare providers.

1.1.1.6 People with PD should be offered an accessible point of contact with specialist services. This could be provided by a Parkinson's disease nurse specialist.

1.1.1.7 All people with PD who drive should be advised to inform the Driver and Vehicle Licensing Agency (DVLA) and their car insurer of their condition at the time of diagnosis.

1.2 Diagnosing Parkinson's disease

1.2.1 Definition and differential diagnosis

1.2.1.1 PD should be suspected in people presenting with tremor, stiffness, slowness, balance problems and/or gait disorders.

1.2.2 Expert versus non-expert diagnosis

1.2.2.1 People with suspected PD should be referred quickly[4] and untreated to a specialist with expertise in the differential diagnosis of this condition.

1.2.3 Clinical versus post-mortem diagnosis

1.2.3.1 PD should be diagnosed clinically and based on the UK Parkinson's Disease Society Brain Bank Criteria.

1.2.3.2 Clinicians should be encouraged to discuss with patients the possibility of tissue donation to a brain bank for purposes of diagnostic confirmation and research.

1.2.4 Review of diagnosis

1.2.4.1 The diagnosis of PD should be reviewed regularly[5] and re‑considered if atypical clinical features develop.

1.2.5 Single photon emission computed tomography (SPECT)

1.2.5.1 123I-FP-CIT SPECT should be considered for people with tremor where essential tremor cannot be clinically differentiated from parkinsonism.

1.2.5.2 123I-FP-CIT SPECT should be available to specialists with expertise in its use and interpretation.

1.2.6 Positron emission tomography (PET)

1.2.6.1 PET should not be used in the differential diagnosis of parkinsonian syndromes, except in the context of clinical trials.

1.2.7 Structural magnetic resonance imaging (MRI)

1.2.7.1 Structural MRI should not be used in the differential diagnosis of Parkinson's disease.

1.2.7.2 Structural MRI may be considered for the differential diagnosis of parkinsonian syndromes.

1.2.8 Magnetic resonance volumetry

1.2.8.1 Magnetic resonance volumetry should not be used in the differential diagnosis of parkinsonian syndromes, except in the context of clinical trials.

1.2.9 Magnetic resonance spectroscopy

1.2.9.1 Magnetic resonance spectroscopy should not be used in the differential diagnosis of parkinsonian syndromes.

1.2.10 Acute levodopa and apomorphine challenge tests

1.2.10.1 Acute levodopa and apomorphine challenge tests should not be used in the differential diagnosis of parkinsonian syndromes.

1.2.11 Objective smell testing

1.2.11.1 Objective smell testing should not be used in the differential diagnosis of parkinsonian syndromes, except in the context of clinical trials.

1.3 Neuroprotection

1.3.1 Vitamin E

1.3.1.1 Vitamin E should not be used as a neuroprotective therapy for people with PD.

1.3.2 Co-enzyme Q10

1.3.2.1 Co-enzyme Q10 should not be used as a neuroprotective therapy for people with PD, except in the context of clinical trials.

1.3.3 Dopamine agonists

1.3.3.1 Dopamine agonists should not be used as neuroprotective therapies for people with PD, except in the context of clinical trials. 

1.3.4 Monoamine oxidase B inhibitors

1.3.4.1 Monoamine oxidase B (MAO-B) inhibitors should not be used as neuroprotective therapies for people with PD, except in the context of clinical trials.

1.4 Pharmacological therapy in early PD

In this guideline, 'early disease' refers to PD in people who have developed functional disability and require symptomatic therapy. 'Later disease' refers to PD in people on levodopa who have developed motor complications.

1.4.1 Choice of initial pharmacotherapy in people with early PD

There is no single drug of choice in the initial pharmacotherapy of early PD. Table 1 may help to guide the reader through the following section.

Table 1 Options for initial pharmacotherapy in early PD

Initial therapy for early PD

First-choice option

Symptom control

Risk of side effects

Motor complications

Other adverse events

Levodopa

Yes

Good degree of symptom control

Evidence of increased motor complications

Evidence of increased other adverse events

Dopamine agonists

Yes

Moderate degree of symptom control

Evidence of reduced motor complications

Evidence of increased other adverse events

MAO-B inhibitors

Yes

Limited degree of symptom control

Evidence of reduced motor complications

Evidence of increased other adverse events

Anticholinergics

No

Lack of evidence

Lack of evidence

Lack of evidence

Beta-blockers

No

Lack of evidence

Lack of evidence

Lack of evidence

Amantadine

No

Lack of evidence

Lack of evidence

Lack of evidence

1.4.1.1 It is not possible to identify a universal first-choice drug therapy for people with early PD. The choice of drug first prescribed should take into account:

  • clinical and lifestyle characteristics

  • patient preference, after the patient has been informed of the short- and long-term benefits and drawbacks of the drug classes.

1.4.2 Levodopa

1.4.2.1 Levodopa may be used as a symptomatic treatment for people with early PD.

1.4.2.2 The dose of levodopa should be kept as low as possible to maintain good function in order to reduce the development of motor complications.

1.4.3 Dopamine agonists

1.4.3.1 Dopamine agonists may be used as a symptomatic treatment for people with early PD.

1.4.3.2 A dopamine agonist should be titrated to a clinically efficacious dose. If side effects prevent this, another agonist or a drug from another class should be used in its place.

1.4.3.3 If an ergot-derived dopamine agonist is used, the patient should have a minimum of renal function tests, erythrocyte sedimentation rate (ESR) and chest radiograph performed before starting treatment, and annually thereafter.[6]

1.4.3.4 In view of the monitoring required with ergot-derived dopamine agonists, a non-ergot-derived agonist should be preferred in most cases.

1.4.4 Monoamine oxidase B inhibitors

1.4.4.1 MAO-B inhibitors may be used as a symptomatic treatment for people with early PD.

1.4.5 Beta-adrenergic antagonists (beta-blockers)

1.4.5.1 Beta-adrenergic antagonists may be used in the symptomatic treatment of selected people with postural tremor in PD, but should not be drugs of first choice.

1.4.6 Amantadine

1.4.6.1 Amantadine may be used as a treatment for people with early PD but should not be a drug of first choice.

1.4.7 Anticholinergics

1.4.7.1 Anticholinergics may be used as a symptomatic treatment typically in young people with early PD and severe tremor, but should not be drugs of first choice due to limited efficacy and the propensity to cause neuropsychiatric side effects.

1.4.8 Modified-release levodopa

1.4.8.1 Modified-release levodopa preparations should not be used to delay the onset of motor complications in people with early PD.

1.5 Pharmacological therapy in later PD

Most people with PD will develop, with time, motor complications and will eventually require levodopa therapy. Adjuvant drugs to take alongside levodopa have been developed with the aim of reducing these motor complications and improving quality of life.

1.5.1 Choice of adjuvant therapy for people with later PD

There is no single drug of choice in the pharmacotherapy of later PD. Table 2 may help to guide the reader through the following section.

Table 2 Options for adjuvant pharmacotherapy in later PD

Adjuvant therapy for later PD

First- choice option

Symptom control

Risk of side effects

Motor complications

Other adverse events

Dopamine agonists

Yes

Moderate degree of symptom control

Evidence of reduced motor complications

Evidence of increased other adverse events

COMT inhibitors

Yes

Moderate degree of symptom control

Evidence of reduced motor complications

Evidence of increased other adverse events

MAO-B inhibitors

Yes

Moderate degree of symptom control

Evidence of reduced motor complications

Evidence of increased other adverse events

Amantadine

No

Non-significant result

Evidence of reduced motor complications

Evidence of increased other adverse events

Apomorphine

No

Limited degree of symptom control

Evidence of reduced motor complications

Evidence of increased other adverse events

1.5.1.1 It is not possible to identify a universal first-choice adjuvant drug therapy for people with later PD. The choice of adjuvant drug first prescribed should take into account:

  • clinical and lifestyle characteristics

  • patient preference, after the patient has been informed of the short- and long-term benefits and drawbacks of the drug classes.

1.5.2 Modified-release levodopa

1.5.2.1 Modified-release levodopa preparations may be used to reduce motor complications in people with later PD, but should not be drugs of first choice.

1.5.3 Dopamine agonists

1.5.3.1 Dopamine agonists may be used to reduce motor fluctuations in people with later PD.

1.5.3.2 If an ergot-derived dopamine agonist is used, the patient should have a minimum of renal function tests, erythrocyte sedimentation rate (ESR) and chest radiograph performed before starting treatment, and annually thereafter[6].

1.5.3.3 A dopamine agonist should be titrated to a clinically efficacious dose. If side effects prevent this, then another agonist or a drug from another class should be used in its place.

1.5.3.4 In view of the monitoring required with ergot-derived dopamine agonists, a non-ergot-derived agonist should be preferred, in most cases.

1.5.4 Monoamine oxidase B inhibitors

1.5.4.1 MAO-B inhibitors may be used to reduce motor fluctuations in people with later PD.

1.5.5 Catechol-O-methyl transferase inhibitors

1.5.5.1 Catechol-O-methyl transferase (COMT) inhibitors may be used to reduce motor fluctuations in people with later PD.

1.5.5.2 In view of problems with reduced concordance, people with later PD taking entacapone should be offered a triple combination preparation of levodopa, carbidopa and entacapone[7].

1.5.5.3 Tolcapone should only be used after entacapone has failed in people with later PD due to lack of efficacy or side effects. Liver function tests are required every 2 weeks during the first year of therapy, and thereafter in accordance with the 'Summary of product characteristics'.

1.5.6 Amantadine

1.5.6.1 Amantadine may be used to reduce dyskinesia in people with later PD.

1.5.7 Apomorphine

1.5.7.1 Intermittent apomorphine injections may be used to reduce off time in people with PD with severe motor complications.

1.5.7.2 Continuous subcutaneous infusions of apomorphine may be used to reduce off time and dyskinesia in people with PD with severe motor complications. Its initiation should be restricted to expert units with facilities for appropriate monitoring.

1.6 Further drug administration considerations

1.6.1.1 Antiparkinsonian medication should not be withdrawn abruptly or allowed to fail suddenly due to poor absorption (for example, gastroenteritis, abdominal surgery) to avoid the potential for acute akinesia or neuroleptic malignant syndrome.

1.6.1.2 The practice of withdrawing patients from their antiparkinsonian drugs (so called 'drug holidays') to reduce motor complications should not be undertaken because of the risk of neuroleptic malignant syndrome.

1.6.1.3 In view of the risks of sudden changes in antiparkinsonian medication, people with PD who are admitted to hospital or care homes should have their medication:

  • given at the appropriate times, which in some cases may mean allowing self-medication.

  • adjusted by, or adjusted only after discussion with, a specialist in the management of PD.

1.6.1.4 Clinicians should be aware of dopamine dysregulation syndrome, an uncommon disorder in which dopaminergic medication misuse is associated with abnormal behaviours, including hypersexuality, pathological gambling and stereotypic motor acts. This syndrome may be difficult to manage.

1.7 Surgery for Parkinson's disease

NICE has also published interventional procedure guidance Deep brain stimulation for Parkinson's disease.

1.7.1 Subthalamic nucleus stimulation

1.7.1.1 Bilateral subthalamic nucleus (STN) stimulation may be used in 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 active mental health problems, for example, depression or dementia.

1.7.2 Globus pallidus interna stimulation

1.7.2.1 Bilateral globus pallidus interna (GPi) stimulation[8] may be used in 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 active mental health problems, for example, depression or dementia.

1.7.3 Comparison of STN and GPi stimulation

1.7.3.1 With the current evidence it is not possible to decide if the subthalamic nucleus or globus pallidus interna is the preferred target for deep brain stimulation for people with PD, or whether one form of surgery is more effective or safer than the other. In considering the type of surgery, account should be taken of:

  • clinical and lifestyle characteristics of the person with PD

  • patient preference, after the patient has been being informed of the potential benefits and drawbacks of the different surgical procedures.

1.7.4 Thalamic stimulation

1.7.4.1 Thalamic deep brain stimulation may be considered as an option in people with PD who predominantly have severe disabling tremor and where STN stimulation cannot be performed.

1.8 Non-motor features of Parkinson's disease

1.8.1 Mental health problems

Depression

1.8.1.1 Clinicians should have a low threshold for diagnosing depression in PD.

1.8.1.2 Clinicians should be aware that there are difficulties in diagnosing mild depression in people with PD because the clinical features of depression overlap with the motor features of PD.

1.8.1.3 The management of depression in people with PD should be tailored to the individual, in particular, to their co-existing therapy. 

Psychotic symptoms

1.8.1.4 All people with PD and psychosis should receive a general medical evaluation and treatment for any precipitating condition.

1.8.1.5 Consideration should be given to withdrawing gradually antiparkinsonian medication that might have triggered psychosis in people with PD.

1.8.1.6 Mild psychotic symptoms in people with PD may not need to be actively treated if they are well tolerated by the patient and carer. 

1.8.1.7 Typical antipsychotic drugs (such as phenothiazines and butyrophenones) should not be used in people with PD because they exacerbate the motor features of the condition.

1.8.1.8 Atypical antipsychotics may be considered for treatment of psychotic symptoms in people with PD, although the evidence base for their efficacy and safety is limited.

1.8.1.9 Clozapine may be used in the treatment of psychotic symptoms in PD, but registration with a mandatory monitoring scheme is required. It is recognised that few specialists caring for people with PD have experience with clozapine.

Dementia

1.8.1.10 Although cholinesterase inhibitors have been used successfully in individual people with PD dementia, further research is recommended to identify those patients who will benefit from this treatment.

1.8.2 Sleep disturbance

1.8.2.1 A full sleep history should be taken from people with PD who report sleep disturbance.

1.8.2.2 Good sleep hygiene should be advised in people with PD with any sleep disturbance and includes:

  • avoidance of stimulants (for example, coffee, tea, caffeine) in the evening

  • establishment of a regular pattern of sleep

  • comfortable bedding and temperature

  • provision of assistive devices, such as a bed lever or rails to aid with moving and turning, allowing the person to get more comfortable

  • restriction of daytime siestas

  • advice about taking regular and appropriate exercise to induce better sleep

  • a review of all medication and avoidance of any drugs that may affect sleep or alertness, or may interact with other medication (for example, selegiline, antihistamines, H2 antagonists, antipsychotics and sedatives).

1.8.2.3 Care should be taken to identify and manage restless legs syndrome (RLS) and rapid eye movement (REM) sleep behaviour disorder in people with PD and sleep disturbance.

1.8.2.4 People with PD who have sudden onset of sleep should be advised not to drive and to consider any occupational hazards. Attempts should be made to adjust their medication to reduce its occurrence.

Daytime hypersomnolence

1.8.2.5 Modafinil may be considered for daytime hypersomnolence in people with PD.

Nocturnal akinesia

1.8.2.6 Modified-release levodopa preparations may be used for nocturnal akinesia in people with PD.

1.8.3 Falls

1.8.3.1 For all people with PD at risk of falling, please refer to Falls: assessment and prevention of falls in older people NICE clinical guideline 21.

1.8.4 Autonomic disturbance

1.8.4.1 People with PD should be treated appropriately for the following autonomic disturbances[9]:

  • urinary dysfunction

  • weight loss

  • dysphagia

  • constipation

  • erectile dysfunction

  • orthostatic hypotension

  • excessive sweating

  • sialorrhoea.

1.9 Other key interventions

1.9.1 Specialist nurse interventions

1.9.1.1 People with PD should have regular access to the following:

  • clinical monitoring and medication adjustment

  • a continuing point of contact for support, including home visits, when appropriate

  • a reliable source of information about clinical and social matters of concern to people with PD and their carers

    which may be provided by a Parkinson's disease nurse specialist.

1.9.2 Physiotherapy

1.9.2.1 Physiotherapy should be available for people with PD. Particular consideration should be given to:

  • gait re-education, improvement of balance and flexibility

  • enhancement of aerobic capacity

  • improvement of movement initiation

  • improvement of functional independence, including mobility and activities of daily living

  • provision of advice regarding safety in the home environment.

1.9.2.2 The Alexander Technique may be offered to benefit people with PD by helping them to make lifestyle adjustments that affect both the physical nature of the condition and the person's attitudes to having PD.

1.9.3 Occupational therapy

1.9.3.1 Occupational therapy should be available for people with PD. Particular consideration should be given to:

  • maintenance of work and family roles, home care and leisure activities

  • improvement and maintenance of transfers and mobility

  • improvement of personal self-care activities, such as eating, drinking, washing and dressing

  • environmental issues to improve safety and motor function

  • cognitive assessment and appropriate intervention.

1.9.4 Speech and language therapy

1.9.4.1 Speech and language therapy should be available for people with PD. Particular consideration should be given to:

  • improvement of vocal loudness and pitch range, including speech therapy programmes such as Lee Silverman Voice Treatment (LSVT)

  • 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 and management to support safety and efficiency of swallowing and to minimise the risk of aspiration.

1.10 Palliative care in Parkinson's disease

1.10.1.1 Palliative care requirements of people with PD should be considered throughout all phases of the disease.

1.10.1.2 People with PD and their carers should be given the opportunity to discuss end-of-life issues with appropriate healthcare professionals. 



[4] The Guideline Development Group considered that people with suspected mild PD should be seen within 6 weeks, but new referrals in later disease with more complex problems require an appointment within 2 weeks.

[5] The Guideline Development Group considered that people diagnosed with PD should be seen at regular intervals of 6–12 months to review their diagnosis.

[6] Full details of the restrictions on pergolide use and monitoring are available in the 'Summary of product characteristics'.

[7] Trade name Stalevo (Orion)

[8] GPi deep brain stimulation is rarely performed for PD in the UK at present, though it is sometimes undertaken when STN deep brain stimulation is not possible.

[9] Please refer to the full Parkinson's disease guideline for additional information.

  • National Institute for Health and Care Excellence (NICE)