The strength of recommendation grading (A–D (GPP)) and level of evidence (1++-4) for interventional studies and strength of recommendation grading A (DS)– D (DS) and level of evidence (Ia–IV) for diagnostic studies are defined at the end of the "Major Recommendations" field.
In addition to evidence-based recommendations, the guideline development group (GDG) also identifies evidence from the National Institute for Health and Clinical Excellence (NICE) guidelines or health technology appraisal programme (NICE).
Communication with People with Parkinson's Disease (PD) and Their Carers
D - Communication with people with PD should be aimed towards empowering them to participate in the judgements and choices about their own care.
D - 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.
D (GPP) - 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
D (GPP) - Families and carers should be given information about the condition, their entitlements to care assessment and the support services available.
D (GPP) - People with PD should have a comprehensive care plan agreed between the individual, their family and/or carers and specialist and secondary healthcare providers.
D (GPP) - 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.
D (GPP) - 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.
Diagnosing Parkinson's Disease
Definition and Differential Diagnosis
D (GPP) - PD should be suspected in people presenting with tremor, stiffness, slowness, balance problems and/or gait disorders.
Clinical Versus Post-Mortem Diagnosis
B (DS) - PD should be diagnosed clinically and based on the UK Parkinson's Disease Society Brain Bank Criteria.
(See Table 5.1 "UK PDS Brain Bank Criteria for the diagnosis of PD" in the original full-length guideline document.)
D (GPP) - Clinicians should be encouraged to discuss with patients the possibility of tissue donation to a brain bank for purposes of diagnostic confirmation and research.
Expert Versus Non-Expert Diagnosis
B (DS) - People with suspected PD should be referred quickly* and untreated to a specialist with expertise in the differential diagnosis of this condition.
*The GDG 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.
Review of Diagnosis
D (DS) - The diagnosis of PD should be reviewed regularly** and reconsidered if atypical clinical features develop.
**The GDG considered that people diagnosed with PD should be seen at regular intervals of 6–12 months to review their diagnosis.
Single Photon Emission Computed Tomography (SPECT)
A (DS) - 123I-FP-CIT [(N-omega-fluoropropyl-2beta-carboxymethoxy-3beta-(4-iodophenyl)tropane)] SPECT should be considered for people with tremor where essential tremor cannot be clinically differentiated from parkinsonism.
D (DS) - 123I-FP-CIT SPECT should be available to specialists with expertise in its use and interpretation.
Positron Emission Tomography (PET)
B (DS) - PET should not be used in the differential diagnosis of parkinsonian syndromes, except in the context of clinical trials.
Magnetic Resonance Imaging (MRI)
B (DS) - Structural MRI should not be used in the differential diagnosis of PD.
D (DS) - Structural MRI may be considered for the differential diagnosis of parkinsonian syndromes.
Magnetic Resonance Volumetry
D (DS) - Magnetic resonance volumetry should not be used in the differential diagnosis of parkinsonian syndromes, except in the context of clinical trials.
Magnetic Resonance Spectroscopy
B (DS) - Magnetic resonance spectroscopy should not be used in the differential diagnosis of parkinsonian syndromes.
Acute Levodopa and Apomorphine Challenge Tests
B (DS) - Acute levodopa and apomorphine challenge tests should not be used in the differential diagnosis of parkinsonian syndromes.
Objective Smell Testing
B (DS) - Objective smell testing should not be used in the differential diagnosis of parkinsonian syndromes, except in the context of clinical trials.
Neuroprotection
Vitamin E
A - Vitamin E should not be used as a neuroprotective therapy for people with PD.
Co-enzyme Q10
B - Co-enzyme Q10 should not be used as a neuroprotective therapy for people with PD, except in the context of clinical trials.
Dopamine Agonists
B - Dopamine agonists should not be used as neuroprotective therapies for people with PD, except in the context of clinical trials.
Monoamine Oxidase Type B Inhibitors
B - MAOB inhibitors should not be used as neuroprotective therapies for people with PD, except in the context of clinical trials.
Symptomatic Pharmacological Therapy in Parkinson's Disease
Early Pharmacological Therapy
Levodopa
A - Levodopa may be used as a symptomatic treatment for people with early PD.
A - The dose of levodopa should be kept as low as possible to maintain good function in order to reduce the development of motor complications.
Dopamine Agonists
A - Dopamine agonists may be used as a symptomatic treatment for people with early PD.
D (GPP) - 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.
D (GPP) - 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. (Full details of the restrictions on pergolide* use and monitoring are available in the Summary of Product Characteristics.)
*Note from the National Guideline Clearinghouse (NGC): On March 29, 2007, Permax (pergolide) was withdrawn from the market in the U.S. and worldwide due to safety concerns of an increased risk of cardiovascular events. See the U.S. Food and Drug Administration (FDA) Web site for more information.
D (GPP) - In view of the monitoring required with ergot-derived dopamine agonists, a non-ergot derived agonist should be preferred in most cases.
Monoamine Oxidase Type B Inhibitors
A - MAOB inhibitors may be used as a symptomatic treatment for people with early PD.
Beta-Adrenergic Antagonists (Beta-Blockers)
D (GPP) - 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.
Amantadine
D (GPP) - Amantadine may be used as a treatment for people with early PD but should not be a drug of first choice.
Anticholinergics
B - 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.
Comparisons of Drug Classes
Modified-Release Compared with Immediate-Release Levodopa
A - Modified-release levodopa preparations should not be used to delay the onset of motor complications in people with early PD.
Choice of Initial Pharmacological Therapy in Early Parkinson's Disease
D (GPP) - 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
Later Pharmacological Therapy
Levodopa
B - Modified-release levodopa preparations may be used to reduce motor complications in people with later PD but should not be drugs of first choice.
Dopamine Agonists
A - Dopamine agonists may be used to reduce motor fluctuations in people with later PD.
D (GPP) - 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. (Full details of the restrictions on pergolide* use and monitoring are available in the Summary of Product Characteristics.)
*Note from the National Guideline Clearinghouse (NGC): On March 29, 2007, Permax (pergolide) was withdrawn from the market in the U.S. and worldwide due to safety concerns of an increased risk of cardiovascular events. See the U.S. Food and Drug Administration (FDA) Web site for more information.
D (GPP) - 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.
D (GPP) - In view of the monitoring required with ergot-derived dopamine agonists, a nonergot- derived agonist should be preferred in most cases.
Monoamine Oxidase Type B (MAOB) Inhibitors
A - MAOB inhibitors may be used to reduce motor fluctuations in people with later PD.
Catechol-O-Methyl Transferase Inhibitors
A - Catechol-O-methyl transferase inhibitors may be used to reduce motor fluctuations in people with later PD.
D (GPP) - 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 (Trade name Stalevo® [Orion]).
D (GPP) - 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.
Amantadine
C - Amantadine may be used to reduce dyskinesia in people with later PD.
Apomorphine
B - Intermittent apomorphine injections may be used to reduce off time in people with PD with severe motor complications.
D - 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.
Choice of Pharmacological Therapy in Later Parkinson's Disease
D (GPP) - 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
D (GPP) - Anti-parkinsonian 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.
D (GPP) - The practice of withdrawing patients from their anti-parkinsonian drugs (so-called 'drug holidays') to reduce motor complications should not be undertaken because of the risk of neuroleptic malignant syndrome.
D (GPP) - In view of the risks of sudden changes in anti-parkinsonian 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
D (GPP) - 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.
Surgery for Parkinson's Disease
Subthalamic Nucleus (STN) Stimulation
D - Bilateral 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
- Have no clinically significant active mental health problems, for example depression or dementia
Globus Pallidus Interna (GPi) Stimulation
D (GPP) - Bilateral GPi 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
- Have no clinically significant active mental health problems, for example depression or dementia
Comparison of Different Types of Deep Brain Stimulation (DBS)
D (GPP) - With the current evidence it is not possible to decide if the STN or GPi is the preferred target for DBS 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 informed of the potential benefits and drawbacks of the different surgical procedures
Thalamic Stimulation
D - Thalamic DBS may be considered as an option in people with PD who predominantly have severe disabling tremor and where STN stimulation cannot be performed.
Non-Motor Features of Parkinson's Disease
Mental Health Problems
Depression
D (GPP) - Clinicians should have a low threshold for diagnosing depression in PD.
D (GPP) - 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.
D (GPP) - The management of depression in people with PD should be tailored to the individual, in particular, to their co-existing therapy.
Psychotic Symptoms
D (GPP) - All people with PD and psychosis should receive a general medical evaluation and treatment for any precipitating condition.
D (GPP) - Consideration should be given to withdrawing gradually anti-parkinsonian medication that might have triggered psychosis in people with PD.
D (GPP) - Mild psychotic symptoms in people with PD may not need to be actively treated if they are well tolerated by the patient and carer.
D (GPP) - 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.
D (GPP) - 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.
B - 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
D (GPP) - 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.
Sleep Disturbance
D (GPP) - A full sleep history should be taken from people with PD who report sleep disturbance.
D (GPP) - 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)
D (GPP) - Care should be taken to identify and manage restless leg syndrome (RLS) and rapid eye movement (REM) sleep behaviour disorder in people with PD and sleep disturbance.
D (GPP) - 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
D (GPP) - Modafinil may be considered for daytime hypersomnolence in people with PD.
Nocturnal Akinesia
D (GPP) - Modified-release levodopa preparations may be used for nocturnal akinesia in people with PD.
Falls
Assessment and Prevention of Falls
(NICE 2004) - For all people with PD at risk of falling, please refer to the National Guideline Clearinghouse summary of the NICE guideline, Clinical practice guideline for the assessment and prevention of falls in older people.
Autonomic Disturbance
D (GPP) - People with PD should be treated appropriately for the following autonomic disturbances:
- Urinary dysfunction
- Weight loss
- Dysphagia
- Constipation
- Erectile dysfunction
- Orthostatic hypotension
- Excessive sweating
- Sialorrhoea
Other Key Interventions
Parkinson's Disease Nurse Specialist Interventions
C - 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.
Physiotherapy
B - 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
C - 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.
Occupational Therapy
D (GPP) - 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
Speech and Language Therapy
Speech and language therapy should be available for people with PD. Particular consideration should be given to:
- B - Improvement of vocal loudness and pitch range, including speech therapy programmes such as Lee Silverman Voice Treatment (LSVT)
- D (GPP) - Teaching strategies to optimise speech intelligibility
- D (GPP) - Ensuring an effective means of communication is maintained throughout the course of the disease, including use of assistive technologies
- D (GPP) - Review and management to support the safety and efficiency of swallowing and to minimise the risk of aspiration
Palliative Care in Parkinson's Disease
D (GPP) - Palliative care requirements of people with PD should be considered throughout all phases of the disease.
D (GPP) - People with PD and their carers should be given the opportunity to discuss end-of-life issues with appropriate healthcare professionals.
Definitions:
Levels of Evidence for Intervention Studies
1++ High quality meta-analysis (MA), systematic reviews (SR) of randomised controlled trials (RCTs), or RCTs with a very low risk of bias
1+ Well conducted MA, SR or RCTs, or RCTs with a low risk of bias
1- MA, SR of RCTs, or RCTs with a high risk of bias
2++ High quality SR of case-control or cohort studies.
High quality case-control or cohort studies with a very low risk of confounding, bias, or chance and a high probability that the relationship is causal
2+ Well conducted case-control or cohort studies with a low risk of confounding, bias, or chance and a moderate probability that the relationship is causal
2- Case-control or cohort studies with a high risk of confounding, bias, or chance and a significant risk that the relationship is not causal
3 Non-analytic studies (for example, case reports, case series)
4 Expert opinion, formal consensus
Levels of Evidence for Studies of the Accuracy of Diagnostic Tests
Ia Systematic review (with homogeneity)* of level-1 studies**
Ib Level-1 studies**
II Level-2 studies***
Systematic reviews of level-2 studies
III Level-3 studies****
Systematic reviews of level-3 studies
IV Consensus, expert committee reports or opinions and/or clinical experience without explicit critical appraisal; or based on physiology, bench research or 'first principles'
*Homogeneity means there are no or minor variations in the directions and degrees of results between individual studies that are included in the systematic review.
**Level-1 studies are studies:
- That use a blind comparison of the test with a validated reference standard (gold standard)
- In a sample of patients that reflects the population to whom the test would apply.
***Level-2 studies are studies that have only one of the following:
- Narrow population (the sample does not reflect the population to whom the test would apply)
- Use a poor reference standard (defined as that where the 'test' is included in the 'reference', or where the "testing' affects the 'reference')
- The comparison between the test and reference standard is not blind
- Case-control studies
****Level-3 studies are studies that have at least two or three of the features listed for level-2 studies.
Classification of Recommendations
Grade A:
- Level 1++ and directly applicable to the target population, or
- Level 1+ and directly applicable to the target population AND consistency of results
- Evidence from National Institute for Health and Clinical Excellence (NICE) technology appraisal
Grade B:
- Level 2 ++, directly applicable to the target population and demonstrating overall consistency of results, or
- Extrapolated evidence from studies rated as 1++ or 1+
Grade C:
- Level 2+, directly applicable to the target population and demonstrating overall consistency of results, or
- Extrapolated evidence from studies rated as 2++
Grade D:
- Level 3 or 4, or
- Extrapolated from 2+, or
- Formal consensus
D (GPP):
A good practice point (GPP) is a recommendation for best practice based on the experience of the Guideline Development Group
Grading of Recommendations on Diagnostic Tests
Grade A (DS) Studies with level of evidence Ia or Ib
Grade B (DS) Studies with level of evidence II
Grade C (DS) Studies with level of evidence III
Grade D (DS) Studies with level of evidence IV
(DS, diagnostic studies)
