Parkinson s disease and primary care

Neurology 427 Parkinson s disease and primary care The publication of the 2006 NICE guidelines for Parkinson s disease may seem to have taken much of the management of patients with Parkinson s disease out of the hands of the GP and put them solely in the care of hospital specialists. However, GP input remains relevant at all stages of the illness. This article aims to highlight where the GP fits into the increasing panel of health professionals caring for patients and their families. Dr Sara Evans* ST5 Geriatric Medicine, Royal United Hospital, Bath Dr Dorothy Robertson Consultant Geriatric Medicine. The Older People s Unit, Royal United Hospital, Bath * email dorothy.robertson@nhs.net Parkinson s disease (PD) is a progressive neurodegenerative condition that should be considered in anyone presenting with tremor, stiffness, slowness, balance problems and/or gait disorders. The motor features of Parkinson s disease result from loss of dopaminergic neurons in the substantia nigra, and need to be distinguished from other causes of parkinsonism such as cerebrovascular disease, dopamine-blocking drug therapy and rarer neurodegenerative conditions. Although the mean age at presentation is 65 years, one in 20 of all newly diagnosed patients are under the age of 40. 1 An average general practice list of 6000 people would expect to have between six and 11 patients with PD. 2 The starting point for diagnosis is the high index of suspicion from the GP, as early symptoms may be subtle and non-specific, particularly in the absence of tremor. One of the main thrusts of the 2006 National Institute for Health and Clinical Excellence (NICE) guidelines is for patients with suspected PD to be referred untreated to a specialist with expertise in the differential diagnosis of this condition, with a target time of six weeks from referral to assessment. 3 This recommendation is based on studies examining the accuracy of diagnosis in different settings. 4 6 Misdiagnosis rates ranged from about 47% of community-diagnosed cases to 25% of cases diagnosed in secondary care without an expert, and only 6 8% of those diagnosed by an expert in movement disorders. NICE also recommends that patients remain under specialist care with review of diagnosis if atypical features develop. The clinical nature of the diagnosis may lead to patients feeling short changed by the lack of structural imaging ( c o m p u t e d t o m o g r a p h y o r m a g n e t i c r e s o n a n c e imaging), but this is only useful for excluding other pathologies, such as vascular parkinsonism. Distinguishing tremor-predominant PD from other tremor syndromes can be tricky and a DaTSCAN (radioisotope scan of dopamine transporters) may then be useful. However, it does not discriminate between PD and the other neurodegenerative p a r k i n s o n i s m s, s u c h a s progressive supranuclear palsy. 5 Drug treatment Drug treatment for PD remains symptomatic, and the NICE recommendation to refer patients untreated reflects the increasing complexity of choice. The decision of what to use and when is individual, and explaining the advantages and disadvantages takes time. Early treatment by the GP can also mask relevant signs and symptoms. Treatment options for early and later PD are listed in Tables 1 and 2. Dopamine agonists tend August 2010 Midlife and Beyond GM

428 Neurology Table 1: Options for treatment in early PD First-choice option Symptom control Motor complications Levodopa/PDI* +++ Dopamine agonists ++ Other adverse events Monoamine oxidase B (MAOB) inhibitors + Anticholinergics Lack of evidence Lack of evidence Lack of evidence β-blockers Lack of evidence Lack of evidence Lack of evidence Amantadine Lack of evidence Lack of evidence Lack of evidence +++ Good degree symptom control; ++ Moderate symptom control; + Limited symptom control; Increased risk; Reduced risk; *levodopa combined with peripheral decarboxylase inhibitor Table 2: Options for treatment in later PD (usually levodopa) Dopamine agonists Catechol-O-methyl transferase (COMT) inhibitors MAOB inhibitors Amantadine Duodopa Tables adapted from the NICE guidance for PD Oral or transdermal patch Apomorphine via intermittent injection or s/c infusion Can reduce dose fluctuations. Consider combination product Stalevo to aid compliance (levodopa/carbidopa/ entacapone) Can reduce dose fluctuations Used to reduce dyskinesia Intraduodenal infusion of levodopa/carbidopa gel to be the first-line choice for younger patients without comorbidity, as they are then less prone to subsequent on/ off fluctuations. However, the side-effect profile of dopamine agonists makes them less suitable for older, frail patients, who are also less likely to develop long-term complications from levodopa therapy. Neuroprotection is still an elusive goal for PD drug research, and vitamins, such as vitamin E and co-enzyme Q10, have not been shown to be effective. 1 Anticholinergic medicines are best avoided in PD due to the effects on cognitive function. Surgery for PD, in the form of deep brain stimulation (DBS), is an option for the management of younger patients who have complex PD; however, referral for this form of surgery should definitely be in the hands of the specialist. Monitoring Changes to drugs used to treat the motor symptoms of PD will mainly take place in secondary care, but many aspects of monitoring and follow-up are best done in partnership with primary care. NICE advocates access to a Parkinson s disease nurse specialist (PDNS), to co-ordinate care so that patients see the right person at the right time. Patients with PD should have ready access to other services including physiotherapy, occupational therapy, speech and language therapy, and social services. 1 Primary care also plays a pivotal role in ensuring that the needs of carers are assessed GM Midlife and Beyond August 2010

Neurology 429 Table 3: Adverse effects of PD medication and how to manage Common to all dopaminergic medication Nausea and vomiting Postural hypotension Somnolence Bad dreams Hallucinations/confusion On/off fluctuations and dyskinesia Individual to dopamine agonists Advise to take food, prescribe domperidone Review medication list. Discontinue other hypotensive agents if possible. Consider fludrocortisone. Specialist advice on reducing PD medicines /+/- midodrine Risk assessment if driving. Medication reduction. Consider change of agent if dopamine agonist seek advice Reduce/stop bedtime PD medication Exclude intercurrent illnesses such as urinary tract infection. Discontinue anticholinergic medicines. Reduce dose and seek specialist advice Seek specialist advice Compulsive behaviour such as pathological gambling or hypersexuality Peripheral oedema Ergot dopamine agonists only. Risk of pulmonary, cardiac and retroperitoneal fibrosis (pergolide, cabergoline, bromocriptine Individual to catechol-o-methyltransferase (COMT) inhibitors Reduce dose and seek advice Seek advice if significant as will need dose reduction/ withdrawal. Check for other causes Yearly monitoring (chest X-ray, echocardiogram and renal function) Red/orange colour to urine Diarrhoea, usually after 1 2 months of treatment Liver failure Individual to MAOB inhibitors Serotonin syndrome Harmless, may stain if incontinent Seek advice. Medication will need to be withdrawn. Settles promptly if due to a COMT inhibitor Tolcapone only requires stringent liver function test monitoring Caution when prescribing with SSRI antidepressants and reviewed throughout disease progression. GPs are well placed to monitor and assist with compliance, and be alert to sideeffects. T a b l e 3 l i s t s t h e dopaminergic side-effects that are common to all PD drugs as well as those problems that are more specific to individual agents. Medication reviews are particularly important, and marrying up the timings of non- PD and PD drugs whenever possible can greatly reduce the burden of these complex drug regimens. Medication must not be stopped abruptly due to the risk of neuroleptic malignant syndrome, and drug holidays are no longer advocated. 1,2 Neuroleptic malignant syndrome consists of pyrexia (>38 oc ), muscle rigidity, autonomic instability and delirium. It is most often seen as a side-effect of dopamine August 2010 Midlife and Beyond GM

430 Neurology -blocking medication, but can also present after the abrupt withdrawal of dopamine or dopamine agonists. Non-motor symptoms The recognition of non-motor symptoms (NMS) in PD is crucial, due to their impact on morbidity. The GP may be the first to be consulted as the patient and carer may not recognise that the symptoms are related to PD. Neuropsychiatric symptoms Impulse control disorders have recently gained notoriety through news reports in the mainstream media. These can manifest as a variety of compulsive behaviours such as gambling, excess shopping and hypersexuality, usually associated with dopamine agonist therapy. Depression occurs in almost half of all patients with PD 2 but we lack an evidence base to guide treatment. There have been few randomised controlled trials that compare treatment classes. Menza et al showed a benefit of nortriptyline over paroxetine for the treatment of depression in patients with both PD and depression. 7 Mirtazapine and venlafaxine are reasonable options as noradrenergic function is reduced more than serotoninergic function in PD depression. Dopaminergic treatment itself can improve mood. 8 Care should be taken when prescribing selective serotonin reuptake inhibitors (SSRIs) concomitantly with monoamine oxidase inhibitors (MAOIs) due to the risk of the serotonin syndrome. PD patients are prone to psychosis and hallucinations, especially in the context of cognitive impairment, concomitant systemic illness or high doses of dopaminergic therapy. The hallucinations are typically visual, and may be tolerated when mild, though a gradual reduction of dopaminergic medication is required if troublesome. Atypical antipsychotics may also be needed, with specialist guidance. Typical antipsychotics are contraindicated due to extrapyramidal side-effects. Cognitive impairment is frequent in PD; up to 80% of patients may develop dementia at some point. 9 Parkinson s disease dementia (PDD) and dementia with Lewy bodies (DLB) can be seen as two ends of a spectrum, dependent on the time of onset of memory impairment. Patients who develop cognitive problems within one year of the onset of motor symptoms are classified as DLB. These conditions are characterised by severe executive dysfunction, with visuospatial i m p a i r m e n t, f l u c t u a t i n g cognitive function, visual hallucinations and delusions. The history is more important than the mini-mental state examination score, which lacks sensitivity for subcortical memory problems. Rivastigmine is currently the only drug licensed for treatment of PDD or DLB. 1 Sleep disorders Sleep disturbance in PD e n c o m p a s s e s d a y t i m e somnolence, rapid eye movement (REM) sleep behaviour disorder (RBD), restless legs syndrome (RLS) and nocturnal akinesia. All PD patients should have a full sleep history taken. In RBD, absence of skeletal muscle atonia during REM sleep causes people to act out their dreams, often violently, and clonazepam may be useful. RLS responds to low-dose dopamine agonists or controlled-release levodopa; ferritin levels should be checked and corrected if low. Bedtime doses of controlledrelease levodopa or dopamine agonists improve nocturnal akinesia, but can provoke bad dreams. Daytime somnolence is a common complaint in PD, due to both the illness and its treatment; a risk assessment is needed if driving. Sedation is especially problematic with certain dopamine agonists, which may be reduced under specialist advice. Modafinil can be considered if patients are difficult to manage, again under specialist advice. 2 Autonomic dysfunction Orthostatic hypotension is common in PD due to the disease and its drug treatment, 10 and comorbidity and over-enthusiastic treatment of hypertension can aggravate the problem. PD patients who fall need assessment for autonomic problems, 11 and all PD patients should have a standing blood pressure measured before instigating or increasing antihypertensive treatment. Increased salt and fluid intake, raising the head of the bed, and the use of fludrocortisone may all be helpful. Midodrine is a specialist, second-line option, though currently unlicensed in the UK. GM Midlife and Beyond August 2010

Neurology 431 Bladder dysfunction affects up to 75% of individuals 2 and management depends on whether the predominant problem is impaired bladder filling (detrusor instability), i m p a i r e d e m p t y i n g (obstructive or neurological) or a combination of the two. Assessment should include physical examination, urinalysis, and monitoring of urinary frequency and volume. Simple measures, such as avoiding c a f f e i n e a n d i n c r e a s i n g daytime fluids, are important. Anticholinergics that cross the blood brain barrier should be avoided; trospium, solifenacin and darifenacin are preferred in the context of PD. Sexual dysfunction is also common, and can be assessed and treated in the same way as for other patients, although hypotensive agents should be prescribed with care. Other problems Unintended weight loss is common in PD; patients may lose as much as 12 kg. 12 Moderate or severe dyskinesia is a risk factor for weight loss, although other medical causes need to be excluded. Swallowing difficulties usually develop in advanced disease, and can lead to aspiration pneumonia, malnutrition and dehydration. A history of coughing with liquids should prompt speech and language therapy referral. The Madopar dispersible preparation is useful when swallow is impaired, or in the acutely unwell patient requiring a nasogastric tube. Rotigotine, a transdermal dopamine agonist preparation, is another option in patients needing to be nil by mouth. The usual side-effect cautions for dopamine agonists apply. Drooling results from reduced swallow rate combined with impaired posture and lip closure rather than excessive saliva, 12 and again referral to speech and language therapy services is beneficial. Hyoscine patches should be avoided or used with great caution as they may provoke hallucinations. Constipation affects up to 60% of patients with PD. 13 Management includes increasing dietary fibre and fluid intake, increasing exercise where possible, and the use of laxatives and stool softeners. Up to 50% of PD patients complain of pain, 2 which is often sensory or neuropathic. It may be related to dose fluctuations, dystonias or feelings of restlessness. Pain occurring at the end of a dose or during the night responds best to changes in PD drugs. Neuropathic pain is more complex to deal with. There are no firm management guidelines, but a stepwise approach, as for other forms of chronic pain, seems sensible. End-of-life issues Parkinson s disease is a progressive disease, though the speed of decline can vary hugely. The principles of palliative care are relevant throughout the course of the disease, the goals being symptom control and the achievement of the best quality of life for patients and their carers. The palliative phase in PD may be years rather than months, and it is helpful for patients and carers to be aware of this and have the opportunity to talk with members of the team looking after them. The GP, who may have cared for the patient and carer for many years, may be a more obvious point of contact for the patient than the hospital team. Realistic goals need to be agreed with the patient, carers and extended multidisciplinary team, including specialist palliative care services, who can be involved in the short or long term. Drugs are commonly reduced in the latter stages of the disease, as the balance between benefit and adverse effects starts to shift. Specific end-of-life issues are also important, such as views on where the patient would like to die, and what treatment they would like in their final days. The National Council for Palliative Care is exploring specific needs for PD patients. 13 Conclusion PD remains a complex and difficult disease to manage, in both primary and secondary care. The NHS Clinical Knowledge Summary (http://www.cks. library.nhs.uk/parkinsons_ disease) is a useful online resource. The Parkinson s UK website provides information for patients as well as professionals (www.parkinsons.org.uk), and its Professional s Guide to Parkinson s Disease (updated in 2007) can be strongly recommended as a practice resource. PD information support workers are employed in August 2010 Midlife and Beyond GM

432 Neurology many areas by Parkinson s UK, and they support patients by providing information and advising about benefit applications and how to deal with social services. Primary care remains central to the support of patients and carers, and GPs should not interpret the NICE guidelines as excluding them from PD patient management. We have no conflict of interest. References 1. The Professional s guide to Parkinson s disease. Parkinson s UK. www.parkinsons.org.uk Novemeber 2007 2. Dodel RC, Eggert KM, Singer MS, et al. Costs of drug treatment in Parkinson s disease. Movement Disorders 1998; 13: 249 254 3. Parkinson s disease: National clinical guidelines for diagnosis and management in primary and secondary care. National Collaborating Centre for Chronic Conditions. Royal College of Physicians. 2006 http://guidance. nice.org.uk/cg35 (accessed 9 August 2010) 4. Meara J, Bhowmick BK and Hobson P. Accuracy of diagnosis in patients with presumed Parkinson s disease. Age Ageing 1999; 28: 99 102 5. Jankovic J, Rajput AH, McDermott MP, Perl DP. The evolution of diagnosis in early Parkinson s disease. Arch Neurol 2000; 57: 369 372 6. Lees AJ, Katzenschlager R, Head J, Ben-Shlomo Y. Ten-year follow-up of three different initial treatments in de-novo PD: a randomized trial. Neurology 2001; 57: 1687 1694 7. Menza M, Dobkin RD, Marin H et al. A controlled trial of antidepressants in patients with Parkinson disease and depression. Neurology 2009; 72: 886 92 8. Shabnam G, Th C, Kho D et al. Therapies for depression in Parkinson s disease. The Cochrane Database of Systematic Reviews 2003; 2: CD003465 9. Aarsland D, Anderson K, L JP et al. Prevalence and characteristics of dementia in Parkinson s disease: an 8-year prospective study. Arch Neurol 2003; 60: 387 392 10. Falls: assessment and prevention of falls in older people. National Institute of Health and Clinical Excellence, 2004, CG21 11. Allcock LM, UllyartL. Kenny RA, Burn DJ. Frequency of orthostatic hypotension in a communityacquired cohort of patients with Parkinson s disease. J Neurol Neurosurg Psychiatry 2004; 75: 1470 1 12. Edwards LL, Pfeiffer RF, Quigley EMM et al. Gastrointestinal symptoms in Parkinson s disease. Movement Disorders 1991; 6: 151 156 13. NCPC survey of end of life care in Parkinson s Disease. www. ncpc.org.uk/policy/pdsurvey.html (accessed 15 July 2010) Box: Long acting dopamine agonists By Dawn Powell, Assistant Editor, GM Cabergoline: in previous years, it was the only long-acting (once-daily) dopamine agonist available. Concerns about the rare ergoline-specific side-effects (eg, heart valve fibrosis) associated with ergot-derived dopamine agonists, such as cabergoline, has limited its use. Rotigotine: Applied as a once-daily transdermal patch, it delivers continuous dopaminergic stimulation over 24 hours. It is indicated as monotherapy for patients with early idiopathic Parkinson s disease or as an adjunct to levodopa for patients with late-stage idiopathic Parkininson s disease. It may be suitable for patients who have difficultly swallowing and it does not interact with food or absorption. Ropinirole prolonged release: a once-daily formulation of ropinirole. It has similar side-effects to the immediate-release version of the drug. It can be used as monotherapy or an adjunct to levodopa in patients with idiopathic Parkinson s disease who are adequately controlled on ropinirole immediate release. Pramipexole prolonged release: a once-daily formulation of pramipexole, it is licensed as initial monotherapy or an adjunct to levodopa. As with ropinirole prolonged release, its side-effect profile is similar to that of the immediate release version. GM Midlife and Beyond August 2010