Practice Guidelines

Diagnosis and pharmacological management of Parkinson’s disease: summary of SIGN guidelines

BMJ 2010; 340 doi: http://dx.doi.org/10.1136/bmj.b5614 (Published 12 January 2010) Cite this as: BMJ 2010;340:b5614
  1. D G Grosset, consultant neurologist1,
  2. G J A Macphee, consultant in medicine for the elderly1,
  3. M Nairn, programme manager2,
  4. on behalf of the Guideline Development Group
  1. 1Department of Neurology, Southern General Hospital, Glasgow G51 4TF
  2. 2Scottish Intercollegiate Guidelines Network, Edinburgh EH7 5EA
  1. Correspondence to: M Nairn moray.nairn{at}nhs.net

    Why read this summary?

    Parkinson’s disease is a common neurodegenerative disease diagnosed in 1% of people aged over 65 years. It has a considerable impact on patients and their families as well as healthcare and social care systems. With an ageing population, the number of cases in Scotland may increase by 30% in the next 25 years.1 Accurate diagnosis can be difficult, particularly at first presentation. As the disease progresses, treatment with complex combinations of drugs often becomes the norm. This article summarises the recommendations from the Scottish Intercollegiate Guideline Network (SIGN) on the diagnosis and drug management of Parkinson’s disease.2

    Recommendations

    SIGN recommendations are based on systematic reviews of best available evidence. The strength of the evidence is graded as A, B, C, or D (fig 1), but the grading does not reflect the clinical importance of the recommendation. Recommended best practice (“good practice points”), based on the clinical experience of the Guideline Development Group, is also indicated (as GPP).

    Figure1

    Explanation of SIGN grades of recommendations

    Diagnosis

    • Diagnosis depends largely on:

      • -The presence of a specific set of clinical features (using research derived diagnostic criteria, such as the UK Brain Bank criteria)3—bradykinesia, rigidity, rest tremor, and postural instability

      • -The absence of atypical features

      • -A slow, progressive course

      • -A good response to drug treatment for Parkinson’s disease.

    • Observe the patient for non-motor features (box), which may predate motor features, particularly impaired olfaction, REM (rapid eye movement) sleep behaviour disorder, constipation, and depression.4 A combination of several such features raises diagnostic suspicion of Parkinson’s disease.

    • Be aware of the potential inaccuracy of clinical diagnosis in the early stages of the disease. For instance, not all patients with parkinsonism have Parkinson’s disease; the term parkinsonism does not specify cause but describes a clinical syndrome of bradykinesia plus at least one of three features: tremor, rigidity, and postural instability. Consider this diagnostic uncertainty when giving information to the patient and planning management.(C)

    • Review the diagnosis regularly by assessing:

      • -Response to treatment

      • -Rate of disease progression

      • -Any new features, some of which may indicate atypical parkinsonism caused by other conditions, such as progressive supranuclear palsy (for example, early swallowing difficulties; gaze paresis) or multiple system atrophy (for example, early severe autonomic problems such as postural hypotension, cerebellar ataxia). (GPP)

    • While basing the diagnosis of Parkinson’s disease on diagnostic criteria, avoid over-rigid application of the criteria. For example, in a patient who develops bradykinesia after taking a drug that may cause parkinsonism, the diagnosis may be Parkinson’s disease, drug induced parkinsonism, both of these, or another cause entirely. (D)

    • Instruct patients diagnosed with Parkinson’s disease to inform the Driver and Vehicle Licensing Agency.

    Major non-motor symptoms of Parkinson’s disease

    Non-motor features may occur at all stages of the disease. Some non-motor features may fluctuate in response to drug treatment, as do motor complications. Non-motor features can be assessed using the non-motor questionnaire from the Parkinson’s Disease Society (www.parkinsons.org.uk/pdf/nms_questionnaire.pdf).

    Neuropsychiatric symptoms
    • Depression, anxiety, apathy

    • Hallucinations, illusions, delusions*

    • Dementia, cognitive impairment*

    • Compulsive and impulsive behaviours*

    Sleep disorders
    • Insomnia*

    • Sleep fragmentation*

    • Excess daytime somnolence*

    • Restless legs syndrome

    • REM (rapid eye movement) sleep behaviour disorder

    • Vivid dreaming*

    • “Acting out” dreams, often including vocalisation when asleep

    Autonomic disorders
    • Bladder disturbance: nocturia, urgency, frequency

    • Heat or cold intolerance*

    • Excess sweating*

    • Orthostatic hypotension*

    • Sexual dysfunction*

    • Drooling of saliva

    Gastrointestinal disorders (overlap with autonomic)
    • Dysphagia

    • Ageusia (absence of taste)

    • Constipation or incomplete emptying of bowel*

    Sensory disorders
    • Pain, paraesthesia

    • Impaired olfaction

    Other symptoms
    • Fatigue*

    • Pain*

    • Diplopia

    • Seborrhoea

    • Weight loss

    • *May be intrinsic to disease and/or precipitated by, or related to, drug treatment for Parkinson’s disease

    Who should diagnose Parkinson’s disease?

    • For all patients presenting to their general practitioner with symptoms suggesting Parkinson’s disease, refer to a hospital clinician with expertise in movement disorders. (C)

    • Do not give a “trial of treatment” before referral as this may mask physical signs; treatment for Parkinson’s disease is rarely required urgently, and no treatment delays disease progression. (C)

    Diagnostic tools

    When the clinical picture is incomplete, or there are pointers to a possible alternative diagnosis, or dual pathology may be present, the following diagnostic tests may be applied.

    • Perform an FP-CIT SPECT (fluoropropyl-carbomethoxy iodophenyl tropane single photon emission computed tomography) brain scan when clinical diagnostic uncertainty exists about the presence of dopamine deficiency as the cause of parkinsonism or tremor. FP-CIT SPECT is abnormal in Parkinson’s disease and other degenerative parkinsonism disorders and is normal in cases of essential tremor, drug induced parkinsonism, and dystonic tremor. (B)

    • Use structural imaging (computed tomography (CT) or magnetic resonance imaging (MRI)) where it would be clinically helpful to identify the presence of structural lesions that may cause or contribute to parkinsonism or tremor. (D)

    • Do not use CT scanning or MRI scanning routinely in diagnosing idiopathic Parkinson’s disease. (C)

    • Use MRI in patients where it would be clinically helpful to identify:

      • -The degree of cerebrovascular disease (in differentiating idiopathic Parkinson’s disease from vascular parkinsonism), or

      • -The degree and distribution of brain atrophy (for example, when clinical features suggest atypical parkinsonism such as multiple system atrophy). (D)

    • Do not use acute dopaminergic challenge testing, transcranial sonography, or objective olfactory testing in routine clinical diagnosis of Parkinson’s disease. (A, B, C)

    Genetic testing

    Nearly all cases of Parkinson’s disease cases arise from no apparent cause (so called sporadic Parkinson’s disease), although genetic susceptibility factors may be relevant.

    • Do not routinely incorporate gene testing of affected individuals or asymptomatic family members for monogenic parkinsonism as no evidence of benefit exists. Refer patients who request genetic testing to a specialist movement disorders clinician for assessment. (GPP)

    Management of non-motor neurobehavioural disorders

    Mood disorders including depression affect 30-50% of patients with Parkinson’s disease.5 However the diagnosis of depression may be difficult in these patients as its features may overlap with those of cognitive impairment or of Parkinson’s disease itself (such as flattened affect, lack of motivation, and reduced motor activity).

    • Use self rating scales (such as the Beck depression inventory or the geriatric depression scale) or clinician rated scales (such as the Hamilton depression rating scale or the Montgomery-Asberg depression rating scale) to screen for depression in patients with Parkinson’s disease.6 Use the Hamilton depression rating scale7 or the Montgomery-Asberg depression rating scale8 to help in determining the severity of depressive symptoms. (C)

    • Do not diagnose depression using rating scales alone. Clinical interview incorporating collateral information from relatives and carers is required. (GPP)

    No specific recommendation can be made for the choice of antidepressant agent as the evidence is limited. Amitriptyline and desipramine are associated with some benefit but carry a risk of adverse effects.9 10 Many other antidepressants (such as selective serotonin reuptake inhibitors) are commonly used.11

    Drug management

    Figure 2 shows an algorithm for drug treatment for Parkinson’s disease.

    Figure2

    Fig 2 Drug treatment algorithm for Parkinson’s disease

    Initial treatment

    • Choose an initial therapeutic agent from the following drug classes:

      • -Dopamine agonists—a non-ergot dopamine agonist (ropinirole, pramipexole, or rotigotine) is preferable to ergot derived agonists (pergolide, cabergoline, bromocriptine) (A)

      • -Levodopa with a dopa-decarboxylase inhibitor (A)

      • -Monoamine oxidase B inhibitors (A)

    • Choose an agent by taking into account its relative efficacy and adverse effect profile; the patient’s comorbidity, employment status, and own drug preference; and the clinician’s experience. Each patient should have individual assessment and discussion.

    • Warn patients about the potential for dopamine agonists to cause impulse control disorders (pathological gambling, binge eating, compulsive shopping, and hypersexuality), and excessive daytime somnolence (and the implications for driving and for operating machinery). (A)

    • Do not use anticholinergic drugs because of the high risk of adverse effects, particularly on cognition. (B)

    Treating advancing disease with motor complications

    Disease progression and treatment with levodopa based drugs are associated with loss of smooth motor control and with the emergence of motor fluctuations and dyskinesia.12 Drug choice depends on clinical experience, comorbidity, and patient preference. There are no robust clinical triggers for adjunctive therapy. The initial choice will be from one of the drug classes below; over time, combinations of drugs from each class may be necessary.

    • Use catechol-O-methyl transferase inhibitors, monoamine oxidase B inhibitors, or dopamine agonists (oral or transdermal) to manage motor complications. (A)

    • Use a non-ergot dopamine agonist (ropinirole, pramipexole, or rotigotine) to manage motor complications. (A)

    • Use apomorphine by subcutaneous infusion for severe motor complications where there are sufficient expertise and resources. (D)

    • In patients with motor fluctuations use catechol-O-methyl transferase inhibitors or intermittent subcutaneous apomorphine to reduce “off” time (that is, symptoms that recur at the end of a dose cycle as the medication effect wears off). (A)

    Neurosurgery can reduce motor fluctuations and dyskinesia, but the selection of appropriate patients is outside the scope of this guideline.

    Intraduodenal levodopa is expensive but may be appropriate in selected patients with advanced motor complications, after other options have been explored. It is not approved by the Scottish Medicines Consortium (which provides advice to Scottish NHS Boards and their area drug and therapeutics committees about all newly licensed medicines).

    Daytime sleepiness

    Up to a half of patients with Parkinson’s disease experience excessive daytime sleepiness.13 14 15

    • Exclude reversible causes of excessive daytime sleepiness—such as depression, poor sleep hygiene, and drugs associated with altered sleep pattern. (GPP)

    • Do not use modafinil or melatonin to reduce excessive daytime sleepiness in people with Parkinson’s disease. (A)

    Dementia

    Dementia is present in at least a third of patients with late Parkinson’s disease.16

    • Withdraw non-parkinsonian drugs with potential adverse effects on cognitive function (such as tricyclic antidepressants). (GPP)

    • Withdraw sequentially and gradually anticholinergic agents, amantadine, selegiline, and dopamine agonists. (GPP)

    • Exclude other causes of cognitive impairment or psychosis, particularly delirium, before adding a specific drug treatment for dementia. (GPP)

    Consider treating patients with mild to moderate dementia (score 10-24 on the mini-mental state examination) and Parkinson’s disease with the cholinesterase inhibitor rivastigmine, although the magnitude of benefit is modest and tremor may be exacerbated and vomiting increased. 9 17 18 19 In the absence of a submission from the holder of the marketing authorisation, the Scottish Medicines Consortium does not recommend rivastigmine for use in the NHS in Scotland for the treatment of mild to moderately severe dementia in patients with idiopathic Parkinson’s disease.

    Psychosis

    • Exclude other treatable causes of psychosis before using antipsychotic drugs. (GPP)

    • Treat with low dose clozapine, monitoring blood tests for leucopenia or agranulocytosis weekly, and with supervision by a registered specialist. (A)

    • If weekly monitoring of blood is not possible, treat with low dose quetiapine instead. (B)

    Overcoming barriers

    Ten to fifteen per cent of patients diagnosed with Parkinson’s disease are managed in primary care, which is associated with a higher rate of diagnostic error than for patients seen in clinics specialising in movement disorders or Parkinson’s disease.20 If hospital referrals are to be increased, with long term follow-up in hospital clinics, reorganisation of services will be needed.

    Psychosis is a key neuropsychiatric feature of Parkinson’s disease and is associated with substantial disability. Clozapine is recommended as effective treatment but can be prescribed only by a specifically licensed physician (usually psychiatrist), and its use in patients with Parkinson’s disease in the United Kingdom is currently minimal. Parkinson’s disease services need better links with psychiatry services for this problem to be tackled.

    Useful resources

    • Parkinson’s Disease Society, Scottish Office (www.parkinsons.org.uk/scotland)—Offers support and information services for people with Parkinson’s disease, professionals, carers, and volunteers; also has a telephone helpline (0808 800 0303) or email pds.scotland{at}parkinsons.org.uk

    • Younger Parkinson’s Network (www.parkinsons.org.uk/advice/younger-people.aspx)—Section of the Parkinson’s Disease Society, Scottish Office , that offers support for younger patients (aged under 60)

    • National Tremor Foundation (www.tremor.org.uk)—Provides help, support, and advice to those of all ages with all forms of tremor; also has a telephone helpline (0800 3288046)

    Further information on the guidance

    Evidence of inconsistent practice that prompted this guideline

    Evidence exists of inaccurate diagnosis of Parkinson’s disease, particularly in community based studies.20 The value of specialist clinics and of diagnostic tests (such as neuroimaging, olfactory testing) was unclear and therefore required assessment for this guideline.

    Many different therapeutic options exist for Parkinson’s disease, and doctors are uncertain about when to start treatment and how to manage evolving motor complications.21 In addition, doctors are increasingly recognising the non-motor features of Parkinson’s disease. It was therefore important to examine evidence for drug treatment options for these clinical features and complications.

    What’s new in the guidance

    This guideline considered studies of new therapeutic options for Parkinson’s disease (including levodopa based infusion) and new data on the timing of initial treatment; it also examined the treatment complications of impulse control (such as pathological gambling). As the field of genetics in Parkinson’s disease is also progressing steadily we evaluated current knowledge on the role of such testing in routine practice.

    Several monogenic causes of Parkinson’s disease have been identified. Between 15% and 25% of patients with Parkinson’s disease have a family history of Parkinson’s disease.22 No evidence of benefit exists for routine testing of affected individuals or of asymptomatic family members. No discriminating clinical features exist to permit targeted gene testing for specific genes. Interpretation of gene test results is affected by variable penetrance and variable disease expression. Individual case management is unchanged by positive identification of genetic parkinsonism; no disease modifying strategies are available for asymptomatic identified family members.

    A narrative review of the qualitative literature identified key themes of concern to patients with Parkinson’s disease and their carers:

    • Communication throughout disease progression

    • Attitudes to drug treatment

    • Information needs in relation to multifaceted areas

    • Family carers’ needs

    • Non-motor symptoms

    • Importance of multidisciplinary team working.

    The review highlighted the importance that health professionals and client groups attribute to multidisciplinary team working, involving allied and other health professionals (such as physiotherapists, occupational therapists, and speech and language therapists), in managing Parkinson’s disease. A multidisciplinary team approach is the preferred choice of both patients and professionals for “best practice” but does not have qualitative research to support this preference. Further work in this area is needed.

    Guideline development

    SIGN guidelines are developed by multidisciplinary guideline development groups with representation from across Scotland. This guideline development group comprised representatives from primary care, neurology, medicine for the elderly, pharmacy, neuropsychology, nursing, and patient representatives.

    The development of the guideline followed established SIGN methodology (www.sign.ac.uk/methodology/index.html). The guideline’s recommendations are based on a systematic review of the evidence on management. We used an explicit search strategy including databases and websites and supplemented by material identified by individual members of the development group.2 This guideline also includes a narrative review of qualitative studies that aimed to identify areas of interest or concern to patients with Parkinson’s disease and which are represented in the published literature.

    The guideline was issued in January 2010 and will be considered for review after three years. Any updates to the guideline in the interim period will be noted on the SIGN website (www.sign.ac.uk).

    Future research areas

    The guideline development group was not able to identify sufficient evidence to answer all of the key questions asked in this guideline. The following areas for further research have been identified:

    • Identification of disease modifying treatments for Parkinson’s disease

    • Identification of more sensitive and specific investigations for diagnosing Parkinson’s disease

    • Characterisation of the monogenic forms of parkinsonism in more detail, specifically with regard to genetic counselling for families

    • Investigation of whether some monogenic forms of parkinsonism are distinct from what is considered to be idiopathic Parkinson’s disease

    • Identification of more effective treatments for motor complications and for cognitive, psychiatric, and other non-motor symptoms

    • Comparison of effectiveness and safety of rasagiline and selegiline in early and advanced Parkinson’s disease

    • Examination of the impact of age on efficacy of drugs used in Parkinson’s disease

    • Identification of better strategies for prognostic modelling to help inform patients and their carers

    • Identification of the most efficient and cost effective model of delivering health care to patients in the UK

    Notes

    Cite this as: BMJ 2010;340:b5614

    Footnotes

    • This is one of a series of BMJ summaries of new guidelines, which are based on the best available evidence; they highlight important recommendations for clinical practice, especially where uncertainty or controversy exists.

    • The members of the Guideline Development Group were Donald Grosset (chair), consultant neurologist, Southern General Hospital, Glasgow; Graeme MacPhee (secretary), consultant in medicine for the elderly, Southern General Hospital, Glasgow; Juliet Brown, information officer, SIGN; Carl Counsell, consultant neurologist, University of Aberdeen; Richard Davenport, consultant neurologist, Western General Hospital, Edinburgh; Phillip Dry, patient representative, Greenock; Alan Dunbar, patient representative, Edinburgh; Jonathan Evans, professor of applied neuropsychology, Gartnavel Hospital, Glasgow, Alison Foster, senior pharmacist, Ayr Hospital, Ayr; Duncan Gray, associate specialist in care of the elderly, Raigmore Hospital, Inverness; Conor Maguire, consultant in medicine for the elderly, Royal Victoria and Western General Hospitals, Edinburgh; Moray Nairn, programme manager, SIGN; Neil Prentice, senior lecturer in old age psychiatry, Murray Royal Hospital, Perth; Edwin Robertson, general practitioner, Alexandria; Stuart Rochow, consultant in medicine for the elderly, Woodend Hospital, Aberdeen; Shona Scott, Parkinsons’s disease nurse specialist, Royal Alexandra Hospital, Paisley; Andrew Sim, Scotland manager, Parkinson’s Disease Society; Graeme Simpson, consultant in geriatric medicine, Royal Alexandra Hospital, Paisley; David Stewart, consultant in medicine for the elderly, Victoria Infirmary, Glasgow; Carol Vennard, Parkinsons’s disease nurse specialist, Southern General Hospital, Glasgow.

    • Contributors: All authors contributed to reviewing the evidence and writing and correcting the article.

    • Funding: No funding was received for writing this summary.

    • Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare that (1) No authors have support from any company for the submitted work; (2) DGG has received honorariums for talks from Boehringer-Ingelheim (BI), GE Healthcare, GlaxoSmithKline (GSK), Teva, and Union Chimique Belge (UCB); has been reimbursed for conference attendance from Teva and UCB; and has received grant support for research staff from GSK and GE Healthcare. GM has participated in advisory boards for BI, GSK, Teva, and Solvay Pharmaceuticals; has received speaker fees from BI, GSK, Orion, and Solvay; and has received travel grants from BI and UCB Pharma. MN has no relationships with any company that might have an interest in the submitted work in the previous three years; (3) their spouses, partners, or children have no financial relationships that may be relevant to the submitted work; and (4) DGG chaired the SIGN guideline development group on diagnosis and pharmacological management of Parkinson’s disease. GM and MN have no non-financial interests that may be relevant to the submitted work.

    • Provenance and peer review: Commissioned; not externally peer reviewed.

    References