Managing Parkinson's disease in the long term

GPs need a modern approach to treating Parkinson's disease, says Dr George Rhind.

Parkinson's disease is a chronic progressive neuro-degenerative condition which results from dopaminergic neuronal loss in the substantia nigra.

By the time that symptoms appear, 80 per cent of striatal dopamine has been lost. The trigger, or cause, has not been identified. The prevalence is approximately 160 per 100,000 of the population and the incidence approximately 20 per 100,000 per year.

Long-term management necessitates a multi-disciplinary approach and attempting to delay the onset of disabling illness through appropriate medical management.

The first important step is the correct diagnosis of the condition and possible differential diagnoses are given in the box below, although this is not exhaustive.

It is important for the GP to refer to a specialist in movement disorders (neurologist or geriatrician) for diagnosis and for initiation of treatment.

Unfortunately, older patients are referred less often to specialist services than younger patients and, as differential diagnosis is as complex and co-morbidities common, there is no justification for this.

All patients should have the benefit of referral for the condition to be managed jointly.

The education of patients in the condition is as important as assessment.

It is time-consuming, but patients benefit from access to a Parkinson's disease nurse specialist.

Physical therapists

Access to physical therapists is very important in the later stages.

The patient should be able to participate in the treatment and management decisions which will be taken over the longer term.

The diagnosis rests on various criteria, but the most important are finding two of the four cardinal features of the disease (see box below).

These must not be in the presence of drugs which can cause extra-pyramidal symptoms, such as metoclopramide, prochlorperazine or a major tranquilliser, even the newer atypical anti-psychotics. In this case the diagnosis may be drug-induced parkinsonism.

If there are pyramidal signs, cerebrovascular parkinsonism must be considered and a CT scan may be indicated to look for further evidence.

It is important that an individualised management plan is agreed with the patient to relieve symptoms, improve abilities, delay complications and minimise the potential side-effects.

Delaying therapy

Not starting therapy until a degree of disability emerges is an option and many patients prefer this route, but there is currently a debate as to whether this is the most appropriate way forward.

However, while neuro-protection (the ability of medication to preserve neuronal function and to prevent further neuronal loss) has not been clinically proven, delaying therapy remains the preferred option.

Levodopa was the earliest effective treatment and was first-line therapy for many years. However, the realisation that long-term use of levodopa produced the side-effects of dyskinesia, on/off phenomena and wearing off, led to the search for other initiating treatments.

The dopamine agonists (DAs) have proved effective in improving motor symptoms, improving quality of life to a similar degree to levodopa and with the advantage of delaying the above motor complications.

A number of these DAs can now be used as mono-therapy.

The non-ergot DAs, pramipexole and ropinirole, are preferred because of the lack of the side-effects of pulmonary fibrosis and retro-peritoneal fibrosis.

The ergot-derived DA, cabergoline, pergolide, bromocriptine and lisuride require monitoring of pulmonary function tests, chest X-ray and U&E as a minimum.

Side-effects

While the side-effects of levodopa are thought to be less frequent in older patients, it is still devastating for an older patient to be disabled by dyskinesia or on/off phenomena. A DA should also be considered in fit, older patients, despite the increased risk of side-effects.

In a study of patients initially treated with ropinirole, they developed a significantly lower incidence of dyskinesias than those initiated with levodopa (52.4 per cent versus 77.8 per cent). The onset of dyskinesia was also delayed (8.6 versus seven years).

Furthermore, there was no significant difference between those who commenced on the ropinirole (versus levodopa) in terms of control of motor symptoms or in activities of daily living at 10 years. By this time the majority of patients on ropinirole had also commenced levodopa, but the total dose was lower than in the levodopa group.

Anti-muscarinics, which have a beneficial effect on tremor, are now largely avoided in view of the recognition that their use is associated with cognitive impairment.

Levodopa is given with a dopa-decarboxylase inhibitor (DDCI), but entacapone, a COMT inhibitor, which reduces the degradation of levodopa in the peripheral system, can also be added to produce a smoother supply of levodopa to the brain and to prolong the action of the drug.

This combination of levodopa, DDCI and COMT inhibitor can be given as a single medication, in both the early and later stages.

Tolcapone is another COMT inhibitor that can be added to levodopa. MAOB inhibitors (MAOB-I) are once again being considered with a new drug rasagiline which is showing benefit in early and late disease. This has been licensed recently in the UK and is still being assessed.

Amantadine is now used more often for its role in reducing dyskinesias induced by levodopa. So, initial treatment should consider if a DA is appropriate, in which case therapy should be started with ropinirole or pramipexole.

Levodopa should be started if a quick response is required, or side-effects to a DA are likely, or a short treatment horizon is expected (very old age, other co-morbidities which may shorten survival). MAOB-I (rasagiline or selegiline) should be used for mild disability in appropriate patients.

As further therapy, increase DA dose, combine levodopa with the DA, add DA to levodopa, add entacapone to levodopa, or consider the role of MAOB-I and amantadine.

Throughout the process the patient will need to discuss changes in their condition, changes in therapy and their concerns about the future. Parkinson's disease nurses, physiotherapists, occupational therapists, speech and language therapists, dietitians, social workers and the voluntary sector (especially Parkinson's Disease Society) will all play a role.

Problems of depression and dementia may need to be addressed.

GPs need to develop a close relationship over the course of the disease.

Treatment is changing and initiation of therapy with levodopa will not be appropriate in a number of patients. Long-term management needs to be considered, rather than quick, symptomatic improvement. A multi-disciplinary approach is essential.

- Dr Rhind is a consultant physician, medicine for the elderly with a special interest in movement disorders at Dumfries and Galloway Royal Infirmary, Dumfries

THE ROLE OF THE GP IN MANAGING PARKINSON'S DISEASE

- Early referral of all patients suspected of Parkinson's disease and before initiation of therapy. Therapy can make the diagnosis even more difficult and, in the case of levodopa, may 'prime' the patients to side-effects.

- Regular reviews to discuss treatment, adverse effects and possible escalation of treatment.

- Contact with specialist service. To discuss further management and the appropriateness of interventions and to provide the additional knowledge regarding the patient and their medical, social and family history.

- To develop a long-term relationship with the patient and carers and continuity of care.

- Managing the additional features of the disease, such as constipation and depression, as well as co-morbidities.

- To provide a palliative care and terminal care service at or near the end of life when a close relationship will be ever more important.

CARDINAL FEATURES

- Tremor - coarse, usually unilateral, 4-6 Hertz, 'pill-rolling', usually worse at rest.

- Bradykinesia/hypokinesia - poor initiation of movement, reduced arm swing on walking, slower or disrupted rhythm on finger tapping, usually unilateral at onset.

- Rigidity - often cog-wheel in character, otherwise lead pipe.

- Postural instability - usually late. If early, must consider other diagnosis.

DIFFERENTIAL DIAGNOSES
- Essential tremor.
- Drug-induced Parkinsonism.
- Multiple system atrophy.
- Cerebrovascular Parkinsonism.
- Progressive supra-nuclear palsy.

REFERENCES

- The PD Consensus Working Group. Bhalia K, Brookes D et al. Hospital Medicine 1998; 59: 469-80

- Parkinson's Aware in Primary Care. The Primary Care Task Force for The Parkinson's Disease Society 2003.

- McMahon D. Evidence of ageism in Parkinson's Disease management by GPs. BMJ.com 17.03.2001 in rapid responses.

- Rascol O et al. Incidence of dyskinesias in a 10-year naturalistic follow-up of patients with early Parkinson's Disease (PD) initially receiving ropinirole or L-dopa. ICPD Berlin (2005).

- Parkinson's Disease Study Group. A controlled randomised, delayed start study of rasagiline in early Parkinson's Disease. Arch Neurol 2004: 61: 561-6.

CORRECTION

The author of the article on the role of CBT in depression (GP, 10 February, page 30) was Dr Lee David, not Dr David Lee.

Have you registered with us yet?

Register now to enjoy more articles and free email bulletins

Register

Already registered?

Sign in

Before commenting please read our rules for commenting on articles.

If you see a comment you find offensive, you can flag it as inappropriate. In the top right-hand corner of an individual comment, you will see 'flag as inappropriate'. Clicking this prompts us to review the comment. For further information see our rules for commenting on articles.

comments powered by Disqus