Medication

OverviewLevodopa/Carbidopa (Syndopa)Dopa agonistsDopaminergics (Amantadine)AnticholinergicsMono Amine Oxidase Type (MAO-B) InhibitorsCOMT InhibitorsOn time and off timeWearing off and Parkinson’s

There are a variety of medications that are used to treat the symptoms of Parkinson’s. However each PwP requires individualized care and treatment. Most of the commercially available medications control Parkinson’s symptoms by increasing levels of dopamine (cursor – a neurotransmitter/ chemical that helps in sending messages) in the brain.

It is imperative to work with one’s healthcare team to find a treatment regimen that works best. The choice of drug depends on the symptoms, presence of other medical problems and age at presentation. It is also advisable that one should never change or stop taking any medication without consulting the doctor/neurologist.

The main aim of drug treatment in Parkinson’s is;

  • To increase the level of dopamine that reaches the brain,
  • Stimulate the parts of the brain where dopamine works, or
  • Block the action of other chemicals that affect dopamine, such as acetylcholine.

Drug treatment in Parkinson’s is prescribed to suit the individual, both in terms of the dosage, the form of the medication (e.g. slow release) and the times the drugs are taken. A combination of different medications is often required to provide the most effective symptom control.

Treatment is generally started with low doses of a drug; this dose is then gradually increased until the required control over the symptoms is achieved. This gradual introduction helps avoid side effects. Nonetheless, some drugs may have unavoidable side effects. Thus it is important to have a thorough consultation with the doctor so as to be aware of and prepared to cope with the same.

The dose and timing of medications may need to be adjusted over time as one’s symptoms change (or side effects occur). Accordingly, one’s doctor will probably want to check one’s response to the medication.

To know more about how one reacts to medication, you can visit our sections –

  • On and Off time  
  • Wearing off and Parkinson’s


PLEASE NOTE :
No two people with Parkinson’s are exactly the same, and each will have a different combination of symptoms and medication. The drugs mentioned here and some of the information related to them may change from time to time.

A quick glance at the drugs/medication available for the management of PD.

  • Levodopa
  • Dopamine agonists
  • Amantadine/ Dopaminergics
  • Anticholinergics
  • Mono Amine Oxidase Inhibitors (MAO-B inhibitors)
  • COMT inhibitors

Levodopa therapy is a principal and most effective medical treatment for Parkinson’s which was introduced in the late 1960s. It successfully provides relief from the main symptoms of the condition and dramatically enhances the life of people with Parkinson’s disease by improving motor function, mobility and enabling participation in everyday activities.

Levodopa is converted to dopamine in the body, which then replenishes the deficiency of dopamine in the brain. Levodopa when given by itself produces nausea and vomiting. Hence it is combined with carbidopa to prevent this side effect.  The addition of carbidopa also prevents its conversion to dopamine in the bloodstream allowing more levodopa availability in the brain.

Levodopa is usually given as a tablet or capsule. The well known Levodopa/carbidopa formulation is Syndopa, Sinemet, Tidomet & Madopar (levodopa + benserazide).

Controlled release preparations of levodopa are recognized by the letters HBS or CR after the drug name. These preparations release the drug over a four to six hour period and may result in more even levels of levodopa in the blood. They may be used when a person with Parkinson’s is experiencing wearing off of the dose of standard levodopa. They can also be taken before going to bed to reduce stiffness and immobility during the night.

Although levodopa remains very effective, with increased dosages and long term treatment people may often experience side effects including dyskinesias (involuntary movements) and on-off fluctuations.

What are the side effects?

  • Nausea and vomiting
  • Reduced appetite
  • A feeling of lightheadedness
  • Fall in blood pressure
  • Dry mouth
  • Dyskinesias (link to dyskinesias)

If one is experiencing any of the above side effects, it’s advisable to consult one’s doctor.

Caution:
Levodopa is also known to interact with other medications like antacids, anti-seizure drugs and drugs that lower blood pressure.

Levodopa and protein interaction

Failure to respond to levodopa may suggest that the condition is not typical Parkinson’s, but a Parkinson’s like condition and further medical assessments may be required.

Dopamine agonists stimulate the dopamine receptors rather than replacing dopamine. Dopamine receptor agonists are drugs that have a structure very similar to dopamine. Because of this similarity, they are able to mimic the action of dopamine rather than replenish the inadequate supply of dopamine in the way levodopa does. They can be taken alone or in combination with levodopa.

Dopamine Agonists include –

  • Ropinirole (Roparl)
  • Pramipexole (like- Pramipex, Pramirol),
  • Rotigotine transdermal system – (on cursor – A drug that is administered via skin patches that is changed every 24 hours)
  • Piribidil ( Trivistal LA)

These drugs are usually started at a low dose and increased slowly to reduce any possible side effects. Dopamine agonists are best taken with meals.

Several clinical studies have shown that dopamine agonists can be an effective treatment for several years when used alone and the likelihood of developing dyskinesias is reduced while people remain on a dopamine agonist alone or in combination with a low dose of levodopa. Thus, enabling the clinician to save levodopa for the later management of Parkinson’s.

What are the possible side effects?

  • Nausea and vomiting
  • Confusion and hallucinations (cursor explaining what is hallucination)
  • Dizziness or lightheadedness
  • Daytime sleepiness
  • Dry mouth
  • Swelling of the ankles
  • Compulsive behaviors (such as uncontrolled shopping, gambling, eating, sexual urges)

If one is experiencing any of the above side effects, it’s advisable to consult one’s doctor.

Caution
Dopa agonists may have interaction with other medications. It is advisable to talk to one’s doctor about the same.

Amantadine is known to promote the release of dopamine and to allow it to stay longer at its site of action. It has been known to produce mild relief that is used in the early stages of Parkinson’s to help with tremor. Amantadine may have a stimulatory effect and can help some people with tiredness or fatigue. It may sometimes help reduce dyskinesias.

Common Amantadine preparations include –Amantrel and Parkitidine

What are the possible side effects?

  • Nausea
  • Insomnia
  • Ankle swelling
  • Dizziness or lightheadedness
  • Skin rash especially in the legs
  • Reduced sensation in feet (inability to feel the ground)
  • Dry mouth
  • Bowel and bladder problems

If one is experiencing any of the above side effects, it’s advisable to consult one’s doctor.

Anticholinergics block the action of acetylcholine, a neurotransmitter that seems to work in balance with dopamine. Because dopamine is in short supply in the brains of people with Parkinson’s, this balance is upset. Blocking acetylcholine restores this balance and helps diminish some of the symptoms of Parkinson’s.

Common Anticholinergic preparations include; Pacitane, Kemadrine, Bexol

Anticholinergics are an older form of medication that are rarely used now although they are sometimes prescribed on their own to treat younger people in the early stages of Parkinson’s who have mild symptoms. They are most effective on tremor. They also may be used to reduce saliva production in people who experience drooling.

They should not be given to older people (above age 60) because there is an increased risk of confusion.

What are the possible side effects?

They can also cause dry mouth, urinary retention, constipation and blurring of vision.

If one is experiencing any of the above side effects, it’s advisable to consult one’s doctor.

Caution

If you have glaucoma you should consult your doctor before taking this drug.

Monoamine oxidase type B inhibitors (MAO-B Inhibitors) inhibit or slow down the metabolism of dopamine, by blocking the enzyme MAO-B; the enzyme that normally breaks down dopamine in the brain.

This activity of MAO-B inhibitors prolongs the potential action of dopamine by increasing the level of natural dopamine (derived from natural levodopa) when used as a treatment in itself.

When used in combination with levodopa medication, it increases the level of levodopa-derived dopamine within the brain, thus making the dose last longer or reduce the amount required. Hence it is now agreed that it produces modest improvements in early stages of Parkinson’s and acts as an adjunct to dopaminergic therapy during the later stages.

MAO-B Inhibitors include Selegiline (like- Selgin, Eldepryl)

What are the possible side effects?

  • Mild nausea
  • Dry mouth
  • Insomnia (for this reason, it is advisable to take the medication as a morning dose)
  • Lightheadedness
  • Confusion (can occur in elderly persons with PD)
  • Hallucinations (can occur in elderly persons with PD)

If one is experiencing any of the above side effects, it’s advisable to consult one’s doctor.

Caution

MAO B inhibitors may have possible interactions with antidepressants and with cold and cough preparations containing dextromethorphan.

These medications have no effect on symptoms of Parkinson’s on their own and are only effective when used in combination with levodopa.

COMT inhibitors work by blocking an enzyme called catechol-O-methyl transferase (COMT) which breaks down levodopa.

As a result they slow the destruction of levodopa in the body allowing more levodopa to pass into the brain to be converted into dopamine. This can improve and lengthen the response to each levodopa dose, thus increasing the amount of time when the symptoms of Parkinson’s disease are well controlled.

These drugs are particularly effective in people who are experiencing on-off fluctuations. (cursor on on-off fluctuations- This refers to the period when people can no longer rely on the smooth and even symptom control that their drugs once gave them which usually occurs after 3-5 years) When used with levodopa, they can reduce the daily off time and increase the on time. In many cases, the levodopa dose and dosing frequency can also be reduced. COMT Inhibitors are also available in combination with Levodopa- Carbidopa.

COMT Inhibitors include; Entacapone (Entacom, Adcapone)

What are the possible side effects?

  • Confusion
  • Hallucinations
  • May increase some levodopa related side effects like dyskinesias
  • Reddish brown discoloration of urine
  • Abdominal pain and diarrhea

If one is experiencing any of the above side effects, it’s advisable to consult one’s doctor.  An increase in side effects after starting a COMT inhibitor should be discussed with the doctor, reducing the levadopa dose can often help in this situation.

Caution

Be aware that other drugs, for Parkinson’s or other conditions, can affect the action of these drugs. Most Parkinson’s drugs can be taken with COMT inhibitors, except Apomorphine.

Please Note
Regular blood tests to monitor liver function are necessary when taking Tolcapone, a type of COMT inhibitor.

When individuals with Parkinson’s start with medications they usually notice that their symptoms reduce for several hours. Movement becomes better, tremor may reduce altogether and walking improves. This is termed as ON time.

OFF time refers to periods in the day when the medication’s effects have reduced and the symptoms may be back altogether. During OFF times, PwPs may experience muscle stiffness, tremor, slowed movements problems with walking – the full range of classic Parkinson’s symptoms. OFF time includes early morning akinesia and lack of movement experienced before taking the first morning dose of medicine. Typically PwPs cycle between their ON and OFF periods three to five times every day, though there may be individual experiences.

It should be kept in mind that this may vary with each individual as each person may react differently to the medication. Also, during the course of the condition, you may observe some fluctuations in your on/off time, which is when you should consult a neurologist.

When a Parkinson’s patient starts treatment with levodopa, the effects are typically dramatic. The bradykinesia (slowness), rigidity and tremor are greatly improved & the person may be almost unaware of his problems. This “levodopa honeymoon” period usually lasts 2 to 5 years. During this time the patient usually does not feel any wearing off of the medication.

As Parkinson’s progresses, PwPs often develop fluctuations in response to medications.  Many PwPs eventually begin to experience a decrease in mobility or an increase in the tremor between doses. Their level of motor function begins to fluctuate. The effects of medication will start to ‘wear off’ earlier than expected, resulting in re-emergence of symptoms. This phenomenon is called as ‘wearing off’.

Wearing off may occur subtly; for example, when a person awakens in the morning and finds that the symptoms of the disease are particularly prominent. He may also experience a return of symptoms prior to the next scheduled dose of medication (end-of-dose motor fluctuations). Some patients experience more abrupt, rapid swings of on/off which may be very unpredictable. They compare their on-off periods to a light switch. When they are ‘on’, their symptoms are very well controlled. When they are ‘off’, however, the Parkinson symptoms are very noticeable.

These fluctuations may be sudden and quite disabling for both the patient and their caregiver.

How do I cope with wearing offs?

The PwP who experiences daily fluctuations in motor performance requires a thorough and accurate assessment of motor function for proper dose adjustment.

  • Wearing-off periods can be improved with appropriate changes in the medication regimen. If one begins to observe a change in one’s response to medications, a fluctuating on/ off period or an earlier return of symptoms, it would be advisable to consult a neurologist.
  • The motor diary is one method of assessing motor function. The patient is asked to record the level of motor function each hour during several 24-hour periods. The physician will then seek to determine a pattern evolving in the person’s motor performance, analyze this performance in relation to medication and adjust the dosage or timing of the medication accordingly. In this way, the physician can best optimize treatment in order to help each patient function at his or her best possible level.


Note
– You could keep a note of your on and off times by means of a diary. Click here to download a Medication Diary for Parkinson’s