Which are the best medications for Parkinson's disease? (Click)

In part 1 of this series, we talked about the "THE BIG ONE" of Parkinson's medications - levodopa. We also talked about levodopa's friend: Entacapone.

In this part we will talk about 3 other very useful medications. The last part (part 3) will discuss medications that are infrequently used for Parkinson's disease.

The lawyer: Amantadine

(Brand names in India: Amantrel, Parkitidin)

How does Amantadine act?

Well, Amantadine is a bit of a wonderful medication. While it can decrease the symptoms of Parkinson's disease, it works best when it is given to support the action of levodopa. In other words: Just like Entacapone, Amantadine is a friend of Levodopa.

While Entacapone can sometimes increase the side-effects of levdopa, Amantadine is the friend who smoothens out your rough edges, makes you a better person. Amantadine decreases some side-effects of levodopa and makes it more wonderful.

Levodopa's two friends: Entacapone & Amantadine.

No one quite understands how Amantadine works for Parkinson's disease. It was originally designed to kill the influenza virus. However, doctors accidentally discovered that it makes Parkinson's disease better as well.

It has one, fantastic and unique effect in Parkinson's disease that is described below.

Use/Advantages:

    1. Treatment of "Dyskinesias": Some patients with Parkinson's disease start getting bothersome movements of the hands, legs and neck after a few years of treatment. I want you to really understand what these movements are like. So with all respect, just for making you visualize these movements properly, please allow me describe these movements in the best way I am able to: these movements are different than the tremor of Parkinson's disease - they are almost dance-like movements, somewhat similar to the way Michael Jackson dances on stage.The latin word for dance is chorea, and therefore these movements are called chorei-form movements. Since that word is very complicated, they are also called "Dyskinesias". These movements are often time-linked to levodopa, so that they are maximum in intensity 30 min - 1 hour after taking levodopa.

      Dyskinesias are dance-like movements.

      Amantadine has one fantastic effect - it decreases these movements tremendously. For patients who have not been able to take enough levodopa because of these movements, it enables intake of an adequate quantity of levodopa, so that they can have a much better quality of life.

    2. It may smoothen-out the effect of levodopa, and can help in relieving "Predictable wearing OFF" to some degree. But, other stratergies such as entacapone, long-acting medications etc are much more useful for this purpose.
    3. Rarely, it can be given as the only medication for Parkinson's disease. But when used by itself, its effectiveness is limited.

Disadvantages:

  1. Most people don't have any side-effects from Amantadine. Some people can have mild swelling or slight purplish discoloration of the feet.
  2. Since it is an anti-viral, it can decrease the effectiveness of some viral vaccines. If a live viral vaccine (e.g. Hepatitis B vaccine) is to be given, Amantadine should be stopped 2 weeks prior and 2 days after the vaccine is administered.

    Amantadine can decrease the effectiveness of some vaccines.

Bottom-line:

It is used to control troublesome dance-like movements caused by high doses of levodopa. Although it is only modestly effective by itself, it is extremely good at smoothing out the rough edges of our superstar (levodopa), hence the sorbiquet - The lawyer of levodopa.

The imitators: Dopamine Agonists: Pramipexole, Ropinirole

(Brand names in India: Pramipex, Pramipex ER, Ropark, Ropark XL)

How do dopamine agonists work?

These chemicals look just like dopamine itself. They attach themselves to the same sites that Dopamine usually attaches itself. This mimicry causes some of the same effects in the brain as dopamine, and relieves some of the symptoms of Parkinson's disease.

Pramipexole (and Ropinirole) looks like Dopamine.

Use/Advantages:

  1. "Extended release" / 24 hour preparations: The main advantage is that these medications have "extended release preparations" that gradually dissolve in the stomach so that they keep gradually entering the blood and then the brain for the entire day. Therefore the effects of a single tablet taken in the morning can last for 24 hours. This is, of course, very convenient! But even more importantly in patients who have Predictable-wearing-OFF or other motor fluctuations with levodopa, these long acting medications can maintain good movement thoughtout the day, to "smoothen out the day".

    The effect of a single tablet of "Extended Release" Pramipexole (or Ropinirole) can last for 24 hours.

  2. They may produce less dyskinesias than levodopa. They may therefore be used to start treatment in younger patients (e.g. below 45) or may be added to the treatment of a person who cannot tolerate high doses of levodopa due to dyskinesias.

Disadvantages:

  1. These medications are not as strong as levodopa. When given in smaller doses, they may not relieve all the symptoms of Parkinson's disease.
  2. When given in higher doses they can produce troublesome side-effects including excessive day-time sleepiness, impulse control problems such as gambling and rarely, sleep disturbances & hallucinations. In particular, the excessive sleepiness during the day often limits their use - restricting their use to smaller doses.

    Rarely, dopamine Imitators can cause Impulse Control Disorders including gambling, excessive spending or excessive eating. But the most common side-effect is sleepiness.

Bottom-line:

While good in theory, it is difficult to use these medications in practice. They are sometimes used for the treatment of very young patients with Parkinson's disease. Also, the fact that 24 hour preparations are available make these medications useful in certain niche situations such as predictable-wearing OFF.

The new kid on the block: Safinamide.

How does Safinamide act?

Safinamide acts just like Rasagiline and Selegiline. It inhibits an enzyme called MAO, which prevents the destruction of dopamine and keeps it in the body for a longer period of time.

It seems to be the less harmful brother of the older brothers Karamazov (Rasagiline & Selegiline), but only time will tell.

This is 2019: Safinamide was released only 4 years ago. No one is perfectly sure how useful it will be.

Uses/Advantages:

  1. Since it is a very new medication, its uses are still being worked out. However, it seems to be effective in late-stage Parkinson's disease. Addition of Safinamide again seems to smoothen-out the effect of levodopa, so that patients experience less fluctuations in their functioning throughout the day.

Disadvantages:

The side-effects of Safinamide seem to be the same as Rasagiline/Selegiline, but they occur less commonly.

  1. Sometimes it can cause high blood pressure, and slightly affect the liver.
  2. More importantly, it can interact with a large number of medications. Although it is probably safer than other similar medications (Rasagiline, Selegiline), you should avoid the following medications while taking it:
    • Some antidepressants including SSRIs (e.g. fluoxetine) and TCAs (e.g. amitriptyline, nortriptyline, amoxapine)
    • Stimulants such as Amphetamine & Methlyphenidate
    • Painkillers that contain opioids
    • Some muscle relaxants such as cyclobenzaprine
    • A few other medications such as the antibiotic linezolid.
    • Possibly, fermented and pickled food e.g. fermented cheeses – although safinamide has not been shown to interact with these things like its brothers rasagiline & selegiline, these are probably best avoided. These can cause a very uncomfortable, and occasionally serious condition called “Cheese reaction” due to accumulation of a chemical called tyramine in the body. The affected person has severe flushing of the skin, his/her heart starts beating faster, and he/she has a marked increase in BP. This can last hours – certainly not a good thing to go through!
Which are the best medications for Parkinson's disease? (Click)