List of drugs used to treat Parkinson’s disease
For those who have developed Parkinson’s disease, the number of “dopaminergic neurons” that make a neurotransmitter called dopamine in the brain is decreasing, which causes various symptoms. Therefore, the main idea of the therapeutic drug is to supplement dopamine first. The table below lists the classifications of therapeutic agents. It also shows a simple effect in parentheses.
| Levodopa, levodopa-containing drug | Levodopa (precursor of dopamine: supplemented with dopamine) Levodopa / carbidopa (suppression of peripheral metabolism of levodopa) Levodopa / benserazide (same as above) Levodopa / carbidopa / entacapone |
| Peripheral COMT inhibitor (suppression of levodopa metabolism in the periphery) | Entacapone |
| Dopamine agonist (similar action to dopamine) Ergot system | Cabergoline Bromocriptine Pergolide |
| Dopamine agonist (similar to dopamine) Non-ergot system | Talipexole Pramipexole Ropinirole Rotigotine Apomorphine |
| Dopamine release promoter (increase dopamine) | Amantadine |
| MAO-B inhibitor (extends the efficacy of dopamine) | Safinamide selegiline rasagiline |
| Anticholinergic drug (When the action of dopamine decreases, acetylcholine increases relatively, so the action due to it decreases) | Trihexyphenidyl piperiden pyroheptin mazaticol |
| Noradrenaline precursor (Dopamine is also a precursor of noradrenaline, so it compensates for the decrease) | Droxidopa |
| Adenosine A2A receptor antagonist (improves movement disorders by non-dopaminergic mechanism) | Istradefylline |
| Dopamine metabolism activator (multi-action such as enhancement of dopamine release, MAO-B inhibitory action, neuroprotective action) | Zonisamide |
Explain the medicines used for each symptom
Symptoms of Parkinson’s disease can be broadly divided into motor and non-motor symptoms.
①: Exercise symptoms are mainly akinesia, tremor, and muscle rigidity (stiffness), and posture maintenance disorder (unbalanced), forward leaning posture, and freezing legs (cannot start walking) may also appear. I have. In other words, it can be said that the motor symptom of Parkinson’s disease is “immobility.”
(2): It is said that most people develop non-motor symptoms, and there are a wide range of disorders such as sleep disorders, mental / behavioral / cognitive disorders, independence neuropathy, and sensory disorders. It is said that this is because the effects of neurodegeneration spread not only to the dopamine nervous system but also to other nervous systems (acetylcholine system, noradrenaline system, serotonin system).
In addition to the symptoms of Parkinson’s disease, treatment-induced motor complications (dyskinesia, dystonia, wear-off, etc.) may also occur.
Below, we will introduce the therapeutic agents and treatment policies for motor and non-motor symptoms, as well as motor complications, as specified in the Parkinson’s Disease Practice Guidelines 2018.
Motor symptoms
According to the treatment algorithm of the guideline, “immobility” due to Parkinson’s disease is first treated with levodopa, dopamine agonists, and MAO₋B inhibitors (depending on complications, age, and severity). And if the symptoms still do not heal, we will continue to use or change other antiparkinsonian drugs. We would like to introduce the following three motor symptoms, as effective therapeutic agents and treatment policies have been reported.
[Tremor]
- Levodopa-containing drug
- Dopamine agonist
- Entacapone
- Anticholinergic drug
- MAO-B inhibitor
- Istradefylline
- Zonisamide
- Β blocker, αβ blocker
- Primidone
- Clonazepam
[Freezing feet]
: If there is no wear-off (described later) → Increase the dose of anti-Parkinson’s disease drug
: There is a wear-off, and the freezing feet
: Appears when the therapeutic drug is working → Droxidopa
: Appears when wearing off → Eliminates wearing off
In addition to the above, some reports have shown that levodopa or dopamine agonists can be improved by reducing the dose, and that Istradefylline and amantadine were effective. Please consult with.
[Posture retention disorder (including forward leaning posture, etc.)]
Postural retention disorders may involve a variety of factors, and there is less evidence regarding treatment. However, if symptoms progress after adding a new drug, it is said that discontinuation of the drug may improve the symptoms.
Non-motor symptoms
There are many cases where the evidence is not sufficient for the treatment of non-motor symptoms, and there are many aspects that rely on empirical treatment. The guidelines summarize the research results as follows.
[Daytime hypersomnia]
: Improvement of night sleep + weight loss of dopamine agonist
[Night sleeplessness]
: Eszopiclone, rotigotine, etc.
[REM sleep behavior disorder]
: Clonazepam
: Rivastigmine, Memantine (not covered by insurance)
[Restless legs syndrome]
: Dopamine agonist
: Gabapentin, pregabalin (not covered by insurance)
[Depressive symptoms]
: Depressive symptoms during wear-off (described later) → Eliminate wear-off
: No wear-off → Pramipexole or antidepressant
[Hallucinations / delusions]
: If it occurs after the drug is added → Discontinuation of the target drug
: Consider reducing or discontinuing medications other than levodopa
(First consider anticholinergic drugs, amantadine, selegiline, then dopamine agonists, and finally discontinue isstradefylline, zonisamide, and entacapone)
: Donepezil, rivastigmine
: Clozapine, quetiapine (not covered by insurance)
[Complications with dementia]
Discontinue anticholinergic drugs and focus on levodopa
Consider the use of donepezil, rivastigmine, memantine
Exercise complications
Describes the symptoms that may occur with the drug and how to deal with them.
[Wearing off]
I mentioned that Parkinson’s disease drugs treat the symptoms of “immobility”, but when the drug is no longer effective, the symptoms will reappear. This is called wear-off (meaning “wears” in English). If a wear-off appears,
: Extends the duration of action of levodopa, suppresses metabolism
: Extends the effectiveness of dopamine
: Consider long-acting dopamine agonists
: Consider administration of istradefylline
[On / Off]
Unlike wearing-off, it means that the symptoms fluctuate as if they were switched on and off, despite the duration of the drug’s effect. This phenomenon is unpredictable and unexplained, and the treatment strategy is not clear. but,
: Selegiline
: There is also a report that it was effective to perform treatment according to wear-off.
[Dyskinesia (involuntary movement)]
: I mentioned that Parkinson’s disease treatments improve the symptoms of “immobility”, but when the amount of dopamine in the brain is adjusted by the drug, “uncontrollable body movements” (dyskinesia) appear along with it. You may. When dyskinesias appear, they often try the following:
: Reduced dose of levodopa
: Reduce daily dose of levodopa and supplement with dopamine agonist
: Dyskinesia-induced drug dose reduction / discontinuation (Istradefylline, MAO-B inhibitor, entacapone)
: Consider administration of amantadine, which has anti-dyskinesia effect
: Dystonia (abnormal muscle tone)
: Symptoms when wearing off → Eliminate wearing off
: Symptoms of the time when the therapeutic drug is effective → Follow the treatment policy of dyskinesia
Is it okay to use Parkinson’s disease medicine together?
First used as a remedy, levodopa has tremendous effect and is quick to work. However, since the duration of the effect is short, wearing-off is likely to appear when used alone. Also, even if you are using a drug with a long duration of action, you may combine it with other drugs due to the appearance of motor complications caused by the therapeutic drug. In other words, Parkinson’s disease is often treated with multiple drugs.
Regarding the concomitant use, caution is required when concomitantly using drugs other than antiparkinson’s disease drugs, such as when treating non-motor symptoms (hallucination, depressive symptoms, etc.). As mentioned above, there are many aspects that rely on empirical treatment and various drugs are used. Therefore, it is advisable to ask the prescribing doctor or pharmacist from time to time whether adverse events (contraindications or side effects) may occur with the combined use of the drug.
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