Parkinson’s treatment with medication

Treatment of Parkinson's disease with medication

Even if we are not yet able to tackle the root of the problem, there are many very good therapies available to alleviate symptoms – so-called symptomatic therapies. First and foremost, dopamine replacement drugs should be mentioned here:

Levodopa (Madopar®, Sinemet®, Carbidopa®/ Levodopa®), which is converted to dopamine in the body, and the dopamine agonists (Sifrol®, Requip®, Neupro®), which bind to dopamine receptors. This strategy of dopamine replacement has been used since the 1970s and is still successfully applied today.

The advantages are obvious: the simple intake of pills or capsules leads to an improvement in quality of life. In the case of levodopa, this is basically also a “natural” approach – similar to replacement therapy for diabetes, which is treated with insulin due to an insulin deficiency.

The dopamine medication replaces the dopamine that has been lost with the disease. The symptoms attributable to the dopamine deficiency improve accordingly.

Opportunities and risks

The extent of the response is variable and – like the disease itself – very individual. We know from experience that tremors are often more difficult to treat than slowness of movement and stiffness. This means that higher doses of medication are often required or, in rare cases, no satisfactory response can be achieved at all. In addition, motor complaints in the center of the body often respond less well than those in the periphery of the body. These are mainly speech disorders, swallowing disorders and balance disorders. The inadequate response can either be explained by the fact that the site where the dopamine should act is also disturbed due to the disease. Alternatively, it is also possible that these symptoms are not due to a dopamine deficiency at all.

On the other hand, dopamine medications often have a positive effect not only on motor function, but also on non-motor complaints in which dopamine deficiency plays a role. A good medication setting can also improve the psyche, sleep or the disturbed perception of pain. If this is the case, we know by implication that these complaints are at least partly due to the dopamine deficiency.

Which dose of a dopamine medication is the right one must be tried out or adjusted individually. There is no blood test that shows how much dopamine is missing. In this respect, there is no limit for too high or too low a dose that applies to all patients. The aim is to replace the amount of dopamine that is missing: too much dopamine increases the risk of side effects. If there is too little dopamine, quality of life is “given away” unnecessarily.

The main side effects of excessive doses are hyperactivity, hallucinations and impulse control disorders.

To put it simply: at this moment, the brain is flooded with too much “lubricant”. Instead of being under-mobile, you are over-mobile; instead of feeling listless, you feel excessively tense and driven.

The thoughts and feelings are so light and fast that this leads to misperceptions (hallucinations) and changes in behavior (impulse control disorders).

Thanks to intensive research, we now know that dopamine medication does not change the course of the disease. This means that they are neither harmful nor do they prevent the disease from progressing. It’s all about improving the quality of life.

The movement disorders

Even if the motor symptoms respond well to dopamine replacement medication, the benefit of drug therapy often diminishes over time. This happens for the following reasons:

1. The duration of the medication’s effect decreases over time. The positive effect wears off more quickly. These phases are referred to as “OFF phases” – in contrast to the good “ON phases”. The intervals between taking medication become shorter in order to have as many ON phases as possible.
2. When the drug starts to take effect in the brain, excessive movements, so-called dyskinesias, increasingly occur, which cannot be suppressed and are characterized by non-rhythmic “fidgeting” (as opposed to rhythmic trembling). These excess movements now represent “bad ON phases” and increasingly alternate with equally bad OFF phases. The good ON phases without excess movements are becoming rarer. We speak of a motor effect fluctuation. Over time, these fluctuations become stronger and more unpredictable. These fluctuations in effect occur when the patient’s own dopamine-producing cells dwindle as the disease progresses and their “buffering capacity” decreases. Suddenly the on and off flooding of the tablets, which themselves only have a limited duration of action, becomes noticeable: Once the dopamine has been used up, the patient becomes immobile or trembles more frequently. If too much dopamine enters the brain, excessive movements occur. We are talking here about a narrowing “therapeutic window”. In addition, the stomach becomes increasingly sluggish, as it is often also affected by Parkinson’s disease. As a result, although patients take their medication regularly, it sometimes remains in the stomach for a long time before it reaches the small intestine, where it is absorbed into the bloodstream and reaches the brain. A protein-rich diet and a change in the intestinal structure can also have a negative effect on absorption into the blood.

All this makes drug treatment increasingly difficult and unreliable. These fluctuations in effect often lead to a considerable deterioration in quality of life. Patients can no longer plan their day well, as they never know if and when they will be well, under- or over-mobile. Patients with severe tremors can no longer perform fine motor tasks well and may become more withdrawn due to the tremors. In this case, the therapy must be adapted in order to maintain a motor condition that is as stable and good as possible. Medication is usually used to try to achieve more stability by taking the tablets more frequently (and therefore with shorter intervals between them) or by combining different preparations.