There is an misconception out there that the drugs only last for 5 or 6 years or so. This is not true, as medications continue to work for as long as they are taken. Due to the progressive nature of the condition the dosages will have to be increased every so often depending upon the level of progression.

Clinical features of Parkinson's disease

These can be divided into motor and non-motor phenomena:

Motor (5 S's) (due to dopamine deficiency)

-    Stiffness

-    Slowness

-    Shake/Tremor

-    Stooped posture

-    InStability

Non-motor (due to dopamine and other chemical deficiencies)

Some of the more important ones include:

-    Depression

-    Poor Memory

-    Urinary Problems

-    Constipation

-    Sexual Problems

-    Low Blood Pressure

-    Sleep Disturbance

When treating Parkinson's disease, physicians sometimes place too much emphasis on the motor symptoms at the expense of the non-motor ones, but it is very important to recognise and effectively treat these other phenomena. Their  relative impact upon the patients' and carers' quality of life can be just as deleterious if not more so occasionally, hence the need for a multidisciplinary team environment.

Judicious use of antidepressants for depression, laxatives, night-time sedatives etc. can often improve the patients' lot, more so than the 'traditional' medications, such as Sinemet, used to treat the slowness and stiffness.

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Treatment of Motor Symptoms

Guiding principles

This depends very much on the age and physical state of the patient. Weighing up the mildness of disease versus the adverse side-effect profile of many of the drugs, we often place people on nothing at all!

To illustrate, we can take the case history of a 'typical' patient:

 1

Mr. J.C. a 55 year old gentleman with no other medical problems. He presents with a six month history of tremor and slowness involving his right arm. After a thorough physical exam, he is given the diagnosis of Parkinson's disease.

What medication to prescribe? This will depend on:

1.    Age

2.    Level of disability.

There is no point getting out the 'big guns' such as Sinemet if the level of disability is slight, but if there are a lot of symptoms and a distinct threat to independence we can use such medication.

Current Possible Options:

1.  Nothing

2.  Eldepryl or Azilect

3.  Dopamine agonists (Mirapexin, and now also available in a one-a-day version,

     Requip (and Requip Modutab, its one-a-day version), Cabaser, Neupro (patch))

4.  Levodopa (Madopar, Sinemet,

     Stalevo)

5.  Symmetrel

 2

Mr. J.C. returns one year after this. He now has some minimal involvement of his right leg and has slowed down over the past year. He works as a builder and finds it difficult to work occasionally.

We decide to put him on a dopamine agonist called Requip. The dose can be gently increased over a number of years in response to changes in your condition.

 3 

Mr. J.C. gets a good response from Requip and continues working. The dose is gradually increased over the next 5 years or so to a maximum tolerated dose due to increasing right-sided symptoms.

He returns to us on a yearly basis.

 4

Mr. J.C., now some 6 years into his condition he states that he cannot keep up with others at work and that it is now taking him an hour to get ready in the mornings. On examination, he also has some involvement of his left side.

 5

Mr. J.C. receives an excellent response from Sinemet over the next 5 years or so, but returns 4 years after commencement of levodopa therapy to state that each dose is not lasting as long as before (wearing off effect).

This is very common and in fact is the norm. Usually, your physician has a number of options. He/she can:

1.  Increase the frequency of your  Sinemet e.g. to 4 or 5 times per day,

2.  Prescribe drugs that can make  the Sinemet last in your system for longer e.g. Comtess or Tasmar or the new drug Stalevo (which is a  combination of Sinemet and Comtess).

The dose of all these drugs can be increased slowly over the years to achieved maximum beneficial effects.

We decide to put him on Stalevo 100 three times daily.

 6

Mr. J.C. returns again some 7 years into his treatment with levodopa (12 years overall), with excess movements involving mainly his arms (dyskinesias).

In general, these are mild and easily treated, but unfortunately sometimes they can become very severe and disabling (hence the reluctance on our part to start using the drug until when absolutely needed). The reasons why they occur are poorly understood, but avoiding high dosages of drugs in the bloodstream seem to help them.

We decide to divide the individual dosages up into smaller ones so that J.C. is taking the same total amount in the day but more frequently, e.g. instead of 100 mg 3 times daily, 50mg six times daily.

Disabling dyskinesias unresponsive to medical therapy can be an indication for referral for surgery.

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Treatment of Tremor

Probably the most difficult symptom to treat in Parkinson's disease. Both Dopamine agonists and Levodopa therapy can help tremor.

Anticholinergics:

Only rarely do we use this group of drugs, e.g., Kemadrin, Akineton. They are good for tremor but have side-effects such as confusion, hallucinations, constipation, urinary problems and many others. They are avoided in general, but are used occasionally in the young and fit.

Severe unresponsive tremor that is physically disabling can be very much improved with surgery.

Extra Information: Side Effects

Nausea: try Motilium; persistent nausea, extra carbidopa might help*.

Neuropsychiatric problems - confusion, psychosis - “quite common in the elderly.” 

Dyskinesias:

 “You usually become dyskinetic at the peak, so reduce the dosage and increase the frequency so you don’t go up as high or down as low.”

“Amantadine (Symmetrel) is also useful... for refractory dyskinesia”, he said, and added that it was also “useful in early disease.”

Apomorphine:

Apomorphine is a “potent dopamine receptor stimulator”, which “could be as potent as levodopa”, but “must be given subcutaneously.” Because of this, its use is “confined to specialist medical clinics and therefore it is underused,” he said, and then added that a carer “can be trained to give injections” which are used intermittently to relieve severe offs.  It can also be delivered via continuous infusion to smooth out the response to levodopa, thus reducing dyskinesias and offs (small pump).

Overview:

- Accurate diagnosis

- Educate, Advise, Motivate

- Nutrition/Antioxidants

- Mental and Physical Exercise

- Pharmacotherapy ONLY when

  functionally impaired

- Start with dopamine agonists

  (younger), levodopa (older)                 

- Dyskinesias/Wearing Off

-       Stalevo

-       Reduce dose/Increase  frequency

-       Amantadine

-       Apomorphine.

AND IN CONCLUSION: Some Basic Principles

Gait/balance problems

    - refer for physiotherapy early

Constipation

    - levodopa not absorbed if   

      constipated  - TREAT!

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*(Brand name Lodosyn;  once only available in the USA from the manufacturer; now available in the USA on prescription, and here on a named patient basis.)

October 2004

The levodopa pump delivery system, Duodopa, is now licensed in Ireland, and one patient has been fitted with the device, which delivers levodopa directly into the duodenum, thus bypassing the stomach and leading to a more continuous supply of levodopa to the brain in the more advanced patient. More details to come.
August 2007