Considerations in the treatment of Parkinson's

disease - how it looks like from the doctor's

                       point of view

                    Dr. Gilad Yahalom

              The Movement Disorders Institue

                      Sheba Medical Center

                                                         part 1

Parkinson's disease (PD) is one of the only neurodegenerative disorders of which there is an effective treatment that alleviates symptoms and enables good quality of life for many years,

although it does not cure the patient .

As for the doctor, the decision what medication should be prescribed is not trivial. The basic instinct is to treat with the most potent and effective medication in order to improve the patient's motor function as much as possible. However, the doctor has to think for the long term and not only to see the best innediate benefit for the moment.

The most effective treatment in the short term is the levodopa derived medications (e.g. Dopicar, Sinemet, levopar, Stalevo). However, over time, its efficacy decreases, and adverse effects appear, including motor fluctuations in the form of "ON" and "OFF" states and involuntary movements (dyskinesias) "ON" state is when the dopaminergic drug is active and the patient feels its effect, and "OFF" state is when the effect of the treatment subsides. As the disease progresses, the OFF states is predominate and the ON states become shorter with a sense of partial effect. As the course further progresses, there appear dyskinesias which initially are not bothering. Sometimer  the patient does not recognize them and they seem from the eyes of the observer as restlessness, but at later stages the dyskinesias become bothersome and even painful. 

Due to the side effects mentioned abobe, the doctor tends to postpone the levodopa treament to more advanced stages, when the less poten medications are no longer effective.

Another component the doctor should into consideration in the decision which medication should be prescribed, is the age of the patient. Some medications can induce memory impairment, confusion and hallucination, particularly in elderly patient or patients with memory deficit.

If the patient is relatively young (less than age 70), who was diagnosed with PD, and the sympoms are not severe, there are several treatment options. For example, initiation of rasagiline (Azilect), a drug which inhibits the breakdown of dopamine, thereby increase the amount of active dopamine. This drug is not particulary potend, but with few side effects. There is also evidence that rasagiline slows down the course of the disease, at    least in the early years, so this is a good choice for first line treatment.

If rasagiline does not alleviate sympotms adequately, anther medication can be added. Amantadine increases dopamine realeas from the dopaminergic cell. It is still a drug with a weaker effect as compared to levodopa, but amantadine is a good alternative in early stages. It is also used in advanced stages at it can reduce dyskinesias. If the patient has tremor as a dominant symptom, anticholinergic agents (Dekinet, Artan, Partan, etc,). Could be a good option, but these drugs can cause memory impaiment, confusion and hallucinations, particularly in the elderly and in patients with pre-existant memory deficit. 

If the first line treatment mentioned above is not effective enough, or it the favoable offect of which subsidesas part of disease progression, treatment with dopaminergic agonists (ropinorole, pramipexole) is a good option. Dopaminergic agonists are relatively potend drugs, and less related yo yhe appearance of motor fluctuations and dyskinesia over time, as compared to the levodopa agents. Dopaminergic agonists activate the receptors that the dopamine normally activates.in PD, the lack of dopamine secondary to the loss of dopaminergic cell is compromised by the boost of synthetic agonists. The use of agonists though should be carefully considered in the elderly and in those with memory impairment due to possible side effects of worsening cognitive function, cofusion and  hallucination, especially in this population. Yet anther significant side effect, although not very common that can occur with the use of dopaminergic agonists, is impluse control diporder. People can spend their money without discretion, in some cases by abusive shopping tours, and in order situation by gambling. In addition, especially in  male, there is a strong sexual urge and sometimes uncontrollable, to the point of embarrassing situation with the partner or with women around. It is important to note that these effect are quite rare and quickly reversible  as soon as the patients and / or their caregivers identify the problem and contact the doctor to modify the treatments. The docyor can decide whetter to decrease the dose or to quit the treatment and predcribe another medication.                                    .