This article is focused on the management of Parkinson's disease. See the separate Parkinsonism and Parkinson's Disease article for further discussion of Parkinson's disease.
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 to involve the carers as much as the patient will allow.
Aims are to communicate information about the disease, help the patient accept the diagnosis, reduce distress and minimise symptoms and, ultimately, 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.
The National Institute for Health and Care Excellence (NICE) recommends using the UK Parkinson's Disease Society (PDS) Brain Bank Criteria for diagnosis.
- Arrange nursing assessment.
- Consider carer support - health and social care assessment.
- Driving - the patient should inform DVLA and insurers.
Non-pharmacological management of motor and non-motor symptoms includes:
- Parkinson's disease nurse specialists.
- Physiotherapy and physical activity.
- Occupational therapy.
- Speech and language therapy.
- Nutritional support.
Aims to establish a care package and lines of communication, 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. NICE suggests review every 6-12 months.
- Assess disability and cognition regularly, both by the patient self-reporting (eg, time how long it takes the patient to walk 20 yards; whether the patient can dress alone; whether he or she can turn over in bed) and by objectively rating motor symptoms (as in the Unified Parkinson's Disease Rating Scale).
- Don't focus solely on motor symptoms - consider other common problems such as sleep disturbance, depression, dementia and psychosis.
- Multidisciplinary management is essential. Ideally, all patients should have access to:
- Nurses with a special interest in Parkinson's disease who can monitor the clinical condition and adjust medication, as well as providing ongoing support for both 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 a handbrake.
- Occupational therapy - give advice and help on 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 the 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 Parkinson's disease may occur.
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 Duodopa® pump treatment in patients with severe motor complication resistant to oral medications. Duodopa® is a formulation of levodopa and carbidopa which is infused into the intestine via a percutaneous endoscopic gastrostomy (PEG) tube. This may provide smoother plasma levodopa levels than oral levodopa, leading to fewer motor fluctuations.
- 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.
- Thalamic stimulation is an alternative for patients with severe tremor who are unsuitable for STN stimulation.
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.
- Referrals may be needed to social services to increase the care package.
- Decide with the patient and family whether referral for a hospice, nursing home or for home palliative care is appropriate.
- Treat any symptoms (eg, pain, anxiety) appropriately and consider withdrawal or reduction of dopaminergic drugs.
There is no universal first-choice drug - this depends on the patient's age, clinical symptoms, lifestyle and personal preferences.
Early untreated Parkinson's disease:
- The choice of drug depends on the impact of improving motor disability (better with levodopa) compared with the risk of motor complications (more common in younger patients) and neuropsychiatric complications (more common in older and cognitively impaired patients; greater with agonists). Options include the following:
- Monoamine-oxidase-B inhibitors (MAO-BIs) - selegiline, rasagiline.
- Oral or transdermal dopamine agonist. Pramipexole, ropinirole and rotigotine are effective. Initial treatment with an agonist is recommended in younger patients.
- Levodopa is the most effective symptomatic drug. The use of controlled-release formulations or adding entacapone is not effective in the delay of motor complications.
- Amantadine or an anticholinergic.
- Ergot derivatives are not recommended as first-line medication because of the risk of fibrotic reactions.
Adjustment of initial therapy in patients without motor complications:
- Patients not on dopaminergic therapy:
- if a patient has started on an MAO-BI, anticholinergic, amantadine or a combination of these, a stage will come when adding levodopa or a dopamine agonist will be required.
- Patients on dopaminergic therapy:
- If on dopamine agonist therapy: increase the dose, switch between agonists, or add levodopa.
- If on levodopa: increase the dose, add an agonist, or add a catechol-O-methyltransferase (COMT) inhibitor.
- Patients with disabling tremor:
- If significant tremor persists: the options are anticholinergics, clozapine, beta-blockers (propranolol) or deep brain stimulation.
Initial drug treatments
- Levodopa should be offered to people in the early stages of Parkinson's disease whose motor symptoms impact on their quality of life.
- A choice of dopamine agonists, levodopa or MAO-BIs should be considered for people in the early stages of Parkinson's disease whose motor symptoms do not impact on their quality of life.
- Levodopa is the most effective drug in the treatment of Parkinson's disease. Virtually all patients respond to it and treatment is associated with reduced morbidity:
- It is given with a peripheral dopa-decarboxylase inhibitor, which prevents peripheral conversion to dopamine. Sinemet® and Madopar® are the main preparations.
- It is usually well tolerated and adverse effects (nausea and dizziness) are quite rare and mild.
- There is no evidence that using modified-release levodopa initially delays onset of motor complications.
- Clinicians should be aware that prolonged levodopa use may be associated with weight loss.
- Dopamine agonists:
- They are effective in treating motor features of Parkinson's disease and can be used in early disease. In the long term they are associated with fewer dyskinesia and motor fluctuations compared with levodopa and may therefore be more appropriate for use in younger patients.
- Acute adverse effects are similar to levodopa but more common and severe and are associated with increased treatment withdrawal and poorer motor scores. These occur at the start of treatment and abate over several days to weeks.
- They are less effective than levodopa, and levodopa is eventually required.
- Prolonged monotherapy (longer than one 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 .
- Non-ergot-derived agonists are preferred (pramipexole and ropinirole).
- Ergot-derived drugs (bromocriptine, cabergoline, lisuride and pergolide) should not be offered as first-line treatment for Parkinson's disease.
- An ergot-derived dopamine agonist should only be used as an adjunct to levodopa for people with Parkinson's disease who have developed dyskinesia or motor fluctuations despite optimal levodopa therapy and whose symptoms are not adequately controlled with a non-ergot-derived dopamine agonist.
- Early treatment with selegiline alone can delay the need for levodopa therapy.
- One study suggested that addition of selegiline to a levodopa/decarboxylase inhibitor combination was more effective when introduced at 5 years than 10 years from the onset of the disease.
- An orally disintegrating formulation increases bioavailability and can be administered at lower doses than conventional selegiline, with similar clinical effect. It also leads to less variable blood concentrations and produces significantly fewer methamfetamine metabolites. It may be especially useful for patients who report adverse events after initial treatment with conventional selegiline or for patients who have swallowing difficulties.
- Rasagiline is a new MAO-BI. Studies suggest it has a protective effect against neurodegeneration and may exert more disease-modifying effects.
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). They are best managed by a specialist.
A choice of dopamine agonists, MAO-B inhibitors or COMT inhibitors should be considered as an adjunct to levodopa for people with Parkinson's disease who have developed dyskinesia or motor fluctuations despite optimal levodopa therapy.
Amantadine should be considered if dyskinesia is not adequately managed by modifying existing therapy. Anticholinergics should not be offered to people with Parkinson's disease who have developed dyskinesia and/or motor fluctuations.
- 'Wearing off' phenomenon - several strategies are available:
- Add in or adjust the dose of dopamine agonist.
- Smaller, more frequent doses of levodopa.
- Prolonged-release levodopa 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 levodopa 30 minutes before food.
- COMT inhibitors (eg, entacapone) can be used to prolong the action of levodopa and increase the 'on time', reduce the levodopa dose and modestly improve motor impairment and disability.
- '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 the levodopa dose and modestly improve motor impairment and disability.
- Fewer doses of levodopa with intermittent injections or subcutaneous infusion of apomorphine.
- Liquid forms of levodopa (enable more close titration of the 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 make it 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 levodopa.
- Surgery may be indicated.
- At the beginning or end of a dose:
- Try soluble levodopa before meals.
- Add a COMT inhibitor.
Patients at higher risk of falling must be referred for rehabilitation, including assessment for physiotherapy and occupational therapy, as early as possible, because anti-Parkinsonian drugs and surgery do not improve gait and posture in Parkinson's disease.
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 selective serotonin reuptake inhibitors (SSRIs) can be used.
- Use tricyclic antidepressants if the sleep pattern is disturbed. Nortriptyline has the lowest anticholinergic effects and so may have the fewest side-effects.
- SSRIs can be helpful if apathy is a predominant feature (but should not be used with selegiline).
- Psychotherapy and support groups are helpful (both for the patient and for carers).
- Cholinesterase inhibitors have been shown to be effective in patients with Parkinson's disease and dementia, with a positive impact on global assessment, cognitive function, behavioural disturbance and activities of daily living rating scales.
- Dopamine agonists have been linked to the development of compulsive or disinhibited behaviours, including pathological gambling, hypersexuality and compulsive eating and shopping, which can have a major impact on the lives of those affected. In rare cases, this may also be observed in some patients on levodopa.
- Patients and their families/carers should be made aware of this potential side-effect and significant behavioural changes should be monitored.
- A patient's drug regime should be reviewed by a Parkinson's disease specialist if compulsive behaviour is observed.
- People with Parkinson's disease who have daytime sleepiness and/or sudden onset of sleep should not drive and should consider any occupation hazards.
- Modafinil can be used to treat excessive daytime sleepiness, only if a detailed sleep history has excluded reversible pharmacological and physical causes.
Rapid eye movement sleep behaviour disorder
- Identify and manage restless legs syndrome and rapid eye movement sleep behaviour disorder (RBD) in people with Parkinson's disease and sleep disturbance.
- Consider clonazepam or melatonin to treat RBD if a medicines review has addressed any possible pharmacological causes.
- Consider levodopa or oral dopamine agonists to treat nocturnal akinesia.
- Consider rotigotine if levodopa and/or oral dopamine agonists are not effective.
- Review existing medicines to address possible pharmacological causes, including antihypertensives (including diuretics), dopaminergics, anticholinergics and antidepressants. Consider treatment with midodrine.
- If midodrine is contra-indicated, not tolerated or not effective, consider fludrocortisone.
Psychotic symptoms (hallucinations and delusions)
- Do not treat hallucinations and delusions if they are well tolerated.
- Reduce the dosage of any Parkinson's disease medicines that might have triggered hallucinations or delusions.
- Consider quetiapine to treat hallucinations and delusions. If standard treatment is not effective, offer clozapine. Lower doses of quetiapine and clozapine are needed than in other indications.
- Other antipsychotic medicines (eg, phenothiazines and butyrophenones) can worsen the motor features of Parkinson's disease.
Drooling of saliva
- Only consider pharmacological management if non-pharmacological management (eg, speech and language therapy) is not available or has not been effective.
- Consider glycopyrronium bromide. If treatment for drooling of saliva with glycopyrronium bromide is not effective, not tolerated or contra-indicated (eg, if cognitive impairment, hallucinations or delusions, or a history of adverse effects following anticholinergic treatment), consider referral to a specialist service for botulinum toxin.
- Only consider anticholinergic medicines other than glycopyrronium bromide to manage drooling of saliva in people with Parkinson's disease if their risk of cognitive adverse effects is thought to be minimal. Use topical preparations if possible (eg, atropine) to reduce the risk of adverse events.
Acute akinesia (Parkinson's crisis)
- A rare but life-threatening complication of Parkinson's disease, with a sudden worsening of motor symptoms and severe akinesia.
- Triggers include infections, surgery, gastrointestinal disease and changes in medication.
- Acute akinesia is difficult to treat and often needs hospital admission.
Adjuvant therapy for more advanced Parkinson's disease
- A choice of dopamine agonists, MAO-BIs or COMT inhibitors should be offered as an adjunct to levodopa for people with Parkinson's disease who have developed dyskinesia or motor fluctuations despite optimal levodopa therapy.
- COMT inhibitors:
- Reversibly inhibit the peripheral breakdown of levodopa 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 a combination drug (levodopa carbidopa entacapone) because of poor patient compliance. One study found that early addition of entacapone to combined therapy produced more benefit than if it were introduced at a later stage (after five years). Tolcapone should only be used if entacapone fails (needs two-weekly LFTs for the first year).
- Antimuscarinic drugs (orphenadrine, procyclidine and trihexyphenidyl) - evidence for efficacy is poor:
- 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 should be considered if dyskinesia is not adequately managed by modifying existing therapy.
- 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.
- Modified-release levodopa can also help with symptom control in later stages.
- For patients who are not candidates for or decline deep brain stimulation (see below), levodopa-carbidopa intestinal gel may be considered. This gel is pumped into the jejunum, via percutaneous tube insertion. It has been approved for the treatment of motor fluctuations in Parkinson disease.
Deep brain stimulation should be considered for people with advanced Parkinson's disease whose symptoms are not adequately controlled by best medical therapy.
- Electrodes are placed in the basal ganglia and attached to an internal stimulator, which is placed subcutaneously below the clavicle.
- May be used to provide unilateral or bilateral stimulation.
- Well-established deep brain stimulation targets include the subthalamic nucleus, the globus pallidus pars interna and, to a lesser degree, the ventral intermediate nucleus of the thalamus. Studies of alternative targets are ongoing. The subthalamus is currently the preferred target for stimulation. It may reverse akinesia, rigidity and tremor.
- Complications include intracerebral haemorrhage and confusion.
- NICE has 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.
Further reading and references
Parkinson's disease; NICE CKS, February 2016 (UK access only)
Parkinson’s disease in adults; NICE guideline (July 2017)
Freitas ME, Fox SH; Nondopaminergic treatments for Parkinson's disease: current and future prospects. Neurodegener Dis Manag. 2016 Jun6(3):249-68. doi: 10.2217/nmt-2016-0005. Epub 2016 May 27.
Titova N, Martinez-Martin P, Katunina E, et al; Advanced Parkinson's or "complex phase" Parkinson's disease? Re-evaluation is needed. J Neural Transm (Vienna). 2017 Dec124(12):1529-1537. doi: 10.1007/s00702-017-1799-3. Epub 2017 Nov 7.
Aragon A, Ramaswamy B, Ferguson J et al; The Professional’s Guide to Parkinson's Disease, Parkinson's UK, 2009
Newman EJ, Breen K, Patterson J, et al; Accuracy of Parkinson's disease diagnosis in 610 general practice patients in the Mov Disord. 2009 Nov 4.
Parkinson’s disease in adults; NICE guideline (July 2017)
Assessing fitness to drive: guide for medical professionals; Driver and Vehicle Licensing Agency
Karlsborg M1, Korbo L, Regeur L, Glad A; Duodopa pump treatment in patients with advanced Parkinson's disease. Dan Med Bull. 2010 Jun57(6):A4155.
Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson’s disease; European Journal of Neurology (Jan 2013)
Bachmann CG, Zapf A, Brunner E, et al; Dopaminergic treatment is associated with decreased body weight in patients with Eur J Neurol. 2009 Aug16(8):895-901. Epub 2009 Apr 3.
Mizuno Y, Kondo T, Kuno S, et al; Early Addition of Selegiline to L-Dopa Treatment is Beneficial for Patients With Parkinson disease. Clin Neuropharmacol. 2009 Nov 21.
Lohle M, Storch A; Orally disintegrating selegiline for the treatment of Parkinson's disease. Expert Opin Pharmacother. 2008 Nov9(16):2881-91.
Olanow CW, Rascol O, Hauser R, et al; A double-blind, delayed-start trial of rasagiline in Parkinson's disease. N Engl J Med. 2009 Sep 24361(13):1268-78.
Clarke CE, Deane KH; Cabergoline for levodopa-induced complications in Parkinson's disease. Cochrane Database Syst Rev. 2001(1):CD001518.
Barbosa AF, Chen J, Freitag F, et al; Gait, posture and cognition in Parkinson's disease. Dement Neuropsychol. 2016 Oct-Dec10(4):280-286. doi: 10.1590/s1980-5764-2016dn1004005.
Rolinski M, Fox C, Maidment I, et al; Cholinesterase inhibitors for dementia with Lewy bodies, Parkinson's disease dementia and cognitive impairment in Parkinson's disease. Cochrane Database Syst Rev. 2012 Mar 143:CD006504. doi: 10.1002/14651858.CD006504.pub2.
Rizek P, Kumar N, Jog MS; An update on the diagnosis and treatment of Parkinson disease. CMAJ. 2016 Nov 1188(16):1157-1165. doi: 10.1503/cmaj.151179. Epub 2016 May 24.
Deep brain stimulation for Parkinson's disease; NICE Interventional Procedure Guidance, November 2003
Sveinbjornsdottir S; The clinical symptoms of Parkinson's disease. J Neurochem. 2016 Oct139 Suppl 1:318-324. doi: 10.1111/jnc.13691. Epub 2016 Jul 11.
Anderson D, Beecher G, Ba F; Deep Brain Stimulation in Parkinson's Disease: New and Emerging Targets for Refractory Motor and Nonmotor Symptoms. Parkinsons Dis. 20172017:5124328. doi: 10.1155/2017/5124328. Epub 2017 Jul 6.
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