MEDICATION EXPLANATIONS – PROS AND CONS

Your neurologist is the best person to advise you about which medication is likely to give you the greatest benefits.  If you choose to use Western medication as part of your journey to better health, seek advice from your chosen neurologist, and be prepared to ask a lot of questions, and keep on asking until you get answers that satisfy you.  Then spend time in considering how YOU feel about their advice.

The information on Western medication contained in these classes is gleaned from respected and commonly used drug guides, medical journals, other medical books as shown, and my experience in clinic since 1998.

The first/primary name shown for each drug is the generic name used by manufacturers, followed by common brand names in brackets. The chemical name, in each case, is long and complicated, so I have refrained from quoting it. The brand names for these drugs may be different in each country and may change from time to time as manufacturers change packaging or marketing policies. There are details of most of the drugs quoted available on the Internet, but more accurate information can be obtained from drug guides available to your doctors and pharmacists.

There are a number of medicines now available to help you control Parkinson’s disease symptoms while you are working to reverse the disease process. These include drugs containing Levodopa (a dopamine precursor), anticholinergic drugs, dopamine agonists, MAO-B inhibitors and COMT inhibitors.

Prior to 1967, the only medications available were amantadine and some anticholinergic drugs. The introduction of levodopa drugs in the 1960’s brought a revolution in the treatment of Parkinson’s disease.  For the first time, many people diagnosed with this distressing disorder were able to gain real relief from many of their symptoms and resume “normal” life for a significant period. Levodopa is the precursor to dopamine and is normally produced in our gut and brain, then converted into dopamine through a fairly complex process.  It is thought (though not yet fully proven) that the levodopa contained in commonly prescribed levodopa drugs is converted to dopamine and utilised in our brain in a similar way to naturally produced levodopa. There are differences and some advantages and disadvantages related to levodopa medication as detailed later.

It is important to note that all medication commonly prescribed for the symptoms of Parkinson’s disease focus, directly or indirectly, on the supply of dopamine to the brain. As discussed in earlier classes, this is not always the most helpful way of treating diagnosed Parkinson’s disease.

AMANTADINE HYDROCHLORIDE (Symmetrel)

The way amantadine works is still not really understood, but it is thought it may enhance dopamine receptor activity and/or slow the reuptake of dopamine in the brain.  In animal studies, Amantadine seemed to increase the release of dopamine in the brain and it is conjectured (but not proven) that it may also do this in the human brain and/or increase release of norepinephrine (noradrenaline).

Amantadine is also used as an anti-viral drug against influenza A but the mechanism of action of this usage is also not really understood, and there is a significant rate of viral resistance to the drug.

There are significant adverse side effects associated with amantadine, including depression, anxiety and confusion, plus many physical discomforts.

ANTICHOLINERGIC DRUGS reduce the amount of available acetylcholine, thus increasing, in relative terms, the amount of dopamine available. This type of drug is used in many aspects of Western Medicine, including cosmetic surgery (Botox), bladder dysfunction (Tolterodine tartrate and Oxybutynin hydrochloride) and Parkinson’s disease.

Common anticholinergic drugs used in Parkinson’s treatment include Benzhexol hydrochloride (Artane), Biperiden hydrochloride (Akineton), Benztropine mesylate (Cogentin and Benztrop).

Again, there is a long list of possible adverse side effects associated with these drugs. Very commonly, patients experience dry mouth, blurred vision, dizziness, mild nausea or nervousness. Others include hallucinations, delusions, agitation and paranoia, plus many physical discomforts.

LEVODOPA DRUGS

The levodopa drugs used in the USA, Canada and Australia are Carbidopa/Levodopa (Sinemet, Atamet, Larodopa, Apo-levocarb, Nu-levocarb, Kinson) and Benserazide hydrochloride/Levodopa (Madopar).  Carbidopa and Benserazide hydrochloride are decarboxylase inhibitors that reduce the amount of levodopa absorbed before crossing into the brain.  Before these decarboxylase inhibitors were added, much of the levodopa taken orally was absorbed into tissue and converted to dopamine before reaching the brain, exacerbating the adverse effects of nausea, and necessitating much higher, more frequent doses to gain reasonable benefit. The decarboxylase inhibitors also prevent reversal of therapeutic effect by Pyridoxine hydrochloride (vitamin B6), which was a challenge prior to their addition to levodopa medications.

In my opinion, levodopa medications are the most, and possibly the only, useful Western drugs for the temporary relief of Parkinson’s disease symptoms. While we understand that dopamine is only one of 40+ neurotransmitters deficient when we exhibit symptoms of Parkinson’s disease, replacement therapy for dopamine does have significant benefits for many people. The drugs must be prescribed/taken cautiously and safety therapies put in place.

A very large study of Parkinson’s disease treatments in 2014 showed that levodopa drugs are still the most effective (and safest) pharmaceutical treatment for long-term control of Parkinson’s disease symptoms (Lancet 2014: 384: 1196-205).

DOPAMINE AGONISTS

Your neurologist may also suggest you start your treatment by taking a dopamine agonist only. Common dopamine agonists are Bromocriptine (Parlodel or Kripton), Pergolide (Permax) and Cabergoline (Cabaser).  These drugs do not supply extra dopamine, but are thought to stimulate dopamine receptors to accept more of the available dopamine. While there are some theoretical advantages in beginning your treatment this way, my experience indicates that the most effective drug treatment is Carbidopa/Levodopa or Benserazide/Levodopa.

Bromocriptine has been shown to exert its effect directly on post-synaptic dopamine receptors in the striatum nigra, but there is no solid research indicating benefit for newly diagnosed patients with Parkinson’s disease. Pergolide has been shown to exert a greater effect on postsynaptic dopamine receptors than Bromocriptine, although there is still no certainty of this direct effect from solid research evidence. Pergolide has not been researched as a stand-alone therapy for Parkinson’s disease either for newly diagnosed, or more advanced patients. There is also a note of caution from the manufacturer about using it in conjunction with Benserazide/Levodopa (Madopar).

Cabergoline seems to have the greatest degree of evidence to support its efficacy in treating those diagnosed with Parkinson’s disease, both newly diagnosed and more advanced. It is used primarily as a first, stand-alone therapy, titrated to a stable level, then levodopa drugs may be added as needed.

Trial evidence looks very encouraging, but clinical experience has shown a somewhat different picture. Those presenting at my clinic taking Cabergoline as their sole therapy, showed rapid onset of adverse effects such as postural hypotension (dropping blood pressure when arising from a chair or bed), depression and, worryingly, pathological gambling. A number of clients gambled away significant savings before any attention was given to this side effect. Most had not even bought lottery tickets before the drug was prescribed. The trials, and clinical practice, have also shown that patients taking Cabergoline will generally require additional levodopa drugs earlier than those taking low-dose levodopa.

All Dopamine Agonists have the potential to create adverse effects such as depression, postural hypotension, dyskinesia, fibrotic disorders and cardiac valve dysfunction. There are many other potential adverse effect including a 3.8% incidence of death in those taking Cabergoline (0% in the placebo group!).

Those taking Dopamine Agonists should ask their doctor about driving or operating machinery, as they may fall asleep suddenly, or find their reflexes are slower than normal.

MONOAMINE OXIDASE INHIBITORS

Selegiline (Elderpryl, Selgene) is a monoamine oxidase B (MAOB) inhibitor that reduces the rate of breakdown of dopamine in the brain, thus making relatively more dopamine available. Your neurologist may prescribe one of these drugs in conjunction with levodopa to keep the dose of levodopa required to a minimum.

Selegiline has been well tested and has been shown to be quite effective at sparing levodopa medication – that is, levodopa dosage may be reduced if Selegiline is used in conjunction. When used as a sole therapy, Selegiline appears to delay the need for levodopa therapy.

Humans express two main types of Monoamine oxidase – A and B. MAOA’s are primarily found in the intestine, while MAOB’s are predominant in the brain. Selegiline is “selective” for MAOB’s (i.e. it mainly inhibits MAOB’s) up to moderate doses. At some unknown level of administration, it becomes “non-selective” and inhibits MAOA’s as well, which can lead to some rather nasty adverse effects.

Selegiline is probably the least toxic of the non-levodopa therapies, but requires caution and strict supervision, as it can create nasty adverse side effects such as depression, confusion, aggression and many physical discomforts.

Rasagiline (Azilect) is a relatively new MAOB inhibitor trialled for the treatment of Parkinson’s disease. Its mechanism of action is not fully understood, and it is only assumed that it is a selective MAOB inhibitor. It is not known to what extent it may also inhibit MAOA. There are a significant number of psychological and physical adverse effects associated with Rasagiline.

Those taking Rasagiline are wise to eat a diet low in tyramine (an amide found in aged and/or fermented foods, especially protein) as the combination may cause dangerous adverse effects including hypertensive crisis that may be very dangerous.

MAOI’s may increase the potency of levodopa medication (as they “spare” dopamine in the brain), so adverse effects may occur sooner or more frequently, necessitating a reduction in levodopa dosage.

If you are taking Selegiline or Rasagiline, DO NOT take antidepressants (MAOI’s or SSRI’s) without making sure that your doctor is aware of possible interactions and synergistic adverse effects, and making sure that it is safe to take both, and that you will be adequately supervised.

COMT INHIBITORS

COMT inhibitors block the action of another chemical (catechol-O-methyl transferase) that breaks down dopamine in the brain.  Tolecapone (Tasmar) was the first drug of this type released, but was withdrawn in Australia and used with caution elsewhere from 1998 after reports of three deaths from hepatitis following use of the drug.  Another COMT inhibitor, Entacapone (Comtan), was released shortly after and is commonly prescribed in conjunction with levodopa drugs.

Entacapone has not been assessed for, and is not recommended as a sole therapy. It is intended to assist those on levodopa medication suffering from significant motor fluctuations and the on/off phenomena. It is thought to increase the bioavailability of levodopa (the amount available for our brain to use) by 5-10% over taking levodopa drugs alone.

As a consequence of its action, the adverse effects of levodopa may be enhanced and so dosage may need to be reduced. The most dangerous effect is a possible increase in somnolence (sleepiness) and sudden onset sleep, which makes it dangerous to drive or operate machinery

SUMMARY

My experience since 1998 indicates that levodopa drugs are still the most effective in reducing the symptoms of Parkinson’s disease.  Dopamine agonists, MAO B inhibitors and COMT inhibitors help some people, but their effect is incremental and there are many people who do not benefit from these additional drugs. Amantadine and anticholinergic drugs usually create more discomfort than the potential benefits are worth.

USING WESTERN MEDICATION

IMPORTANT: If you are considering the use of any Western medication to ease your symptoms, ask your doctor or specialist for the FULL description from his/her major drug guide. I have found that information sheets generally handed out to patients do not contain full precautionary notes, nor full lists of possible adverse effects and/or interactions with other drugs, herbs and supplements. Drug guides, available to health practitioners and pharmacists, contain full descriptions of actions, indication, precautions and adverse effects. You need this information if you are to make an informed choice about whether or not to take Western medication. If your doctor will not or cannot provide this, ask your pharmacist or find another doctor. Do not take any drug unless you have fully informed yourself.

WHAT DRUGS SHOULD I TAKE?

Earlier in this class, we discussed the actions of, and evidence for the drugs commonly available to ease your Parkinson’s disease symptoms. There are some important points to note:

1. Do not stop taking prescribed drugs without seeking advice from a skilled health practitioner.
2. Do not stop taking prescribed drugs when you begin this Recovery Program.
3. Never stop taking prescribed drugs suddenly or quickly unless they are creating a life-threatening situation, or seriously damaging your health.
4. Always reduce prescribed drug intake very slowly to allow your body to become used to the reduced drug support.
5. This Parkinson’s Recovery Program can work for a long time while you are taking prescribed drugs. When your body has become strong/healthy enough, you may reduce your drug intake slowly under supervision.

As stated earlier, I believe the levodopa drugs to be the most useful and least potentially toxic of all those drugs offered. There have been some excited media released about “new, break-through drug therapies” for Parkinson’s disease over recent years (e.g. Stalevo), but, when analysed, we find that the “new drugs” are simply old drugs repackaged (Stalevo = Sinemet + Comtan) or a new type of an old style of drug (Azilect is simply another MAO B inhibitor with not much evidence).

If you are taking a number of drugs (Polypharmacy), either for Parkinson’s disease or a number of health conditions, don’t worry. As you move towards good health, you will be able to, very slowly, reduce the dose and/or frequency of many.

One of the Australians who has recovered was on 11 different drugs when he began the program. These ranged from Parkinson’s disease drugs, anti- hypertensives, anti-nausea to antidepressants. Today, he has no Parkinson’s disease symptoms, and takes only two low-dose drugs for mild hypertension and sleep. The reduction in his drug load took over five years, and there were no adverse effects from reducing doses and/or ceasing drugs under supervision.

You can do this too, but don’t be impatient. First, let’s manage the drugs you have, gain wellness, confidence and strength, then slowly reduce the drug load.

PRESERVING THE USEFULNESS OF L’DOPA

When taking any levodopa drug (Kinson, Madopar, Atamet, Larodopa, Apo-levocarb, Nu-levocarb or Sinemet) it is very important to protect yourself against long-term damage caused by the breakdown of dopamine in the brain.  If protective measures are taken, your levodopa drugs will be more effective for a longer period, and you may be able to stay on a lower dose than otherwise.

When l’dopa is converted to dopamine in the brain, the dopamine is utilised and broken down to a number of different chemical compounds; a few of these metabolites (breakdown products) may be harmful to brain cells.  Some metabolites such as 6 hydroxy-dopa, other quinones and free radicals are thought to both damage cells and slow the conversion of l’dopa to dopamine.  Our best protection against these effects is consumption of therapeutic doses of vitamin C and Folinic Acid (or 5-methyltetrahydrofolate), and hydrating our cells.  Vitamin B complex will also be helpful in protecting cell integrity, assisting cell division and reducing our stress response levels.

A very important metabolite of dopamine use is homocysteine. Homocysteine is a normally produced chemical in our body as we produce and utilise l’dopa naturally. However, when we are healthy, we mop up homocysteine using Folinic Acid, vitamin C and other elements, all of which are in short supply when we manifest the symptoms of Parkinson’s disease. The homocysteine is changed into methionine and used to create other useful chemicals. However, when in excess – that is, when we lack the Folinic Acid, vitamin C, etc required to change it -, homocysteine is implicated in a number of degenerative processes including heart disease and neurological disorders. 

We can slow this process down by reducing the amount of homocysteine hanging around quite easily.

If you are taking any l’dopa drug, always take the following supplements:

Folinic acid                  800-1000 mcg daily with food

Or Folate (5-methyltetrahydroifolate) 1000 mcg (1 mg) daily with food)

Vitamin C                    at least 2000 mg twice daily, increasing to bowel tolerance (class 6)

Vitamin B complex     1 high potency tablet daily.

You may find it more convenient to take one of the “anti homocysteine” preparations available from some naturopaths and health food stores.  Most Anti-Homocysteine Factor preparations contain Foliinic Acid, plus synergistic elements to increase its effectiveness, including vitamin B6.  I suggest that you also take vitamin C as noted above if you use a preparation like this.

Prior to the packaging of levodopa with a decarboxylase inhibitor, vitamin B6 (pyridoxine hydrochloride) inhibited the absorption and utilisation of the drug.  However, studies have shown that it is now quite safe to take vitamin B6 with Levodopa drugs as there is no change in absorption rates.

DOSAGE

When prescribing levodopa drugs, most neurologists ask you to start with a small dose (50 mg or 100 mg) two or three times daily, increasing the dose by 50 or 100 mg each few days or each week until a reasonable reduction in symptoms is achieved.  Most will say nothing about taking Foliinic Acid, vitamin C or any other supplement.

In my experience, it is better to stay on a very low dose (50 mg three times daily) for six to eight weeks before increasing the dose.  Little, if any, benefit will be felt for the first three or four weeks but, after that, there will most likely be a gradual increase in benefit.  You may find that you can maintain this low dose for many months, or need only a very small increase in the amount taken.

Increases in dosage should also be maintained for at least four weeks before any change.  Changes in Parkinson’s disease symptoms happen very slowly, and our response to both Western and Complementary medicine is no different – it happens slowly.

The disadvantage of using a low dose of levodopa over a long period is that symptom relief will take much longer to happen.  But the advantage is that you can stay on a low dose for much longer, thus reducing the adverse effects of the drug, decreasing the need for other drugs to be taken in conjunction with your levodopa, and giving your body a much greater chance of reversing your symptoms.

TIME OF DOSE

Your doctor may insist on you taking your dose of levodopa at a set time each day without variation.  You may find, however, that your response to the medication, and your need for the next dose, varies from day to day.  This can occur with changes in activity, stress levels, foods eaten and even weather conditions.

You may decide to spend some extra time in bed on weekends, or perhaps you are on holidays and starting your day more slowly.  At these times, you may decide to take your first dose for the day a little later.  Your need for the second and third dose may vary by one or two hours, and you are the best judge of this.

I suggest that you, initially, take your levodopa strictly to the timetable set out by your doctor.  Observe closely how long it takes for each dose to have a beneficial effect, how long it lasts, and the signs that your medication is wearing off (your Journal will be very helpful for this).  Once you understand your individual response, you are in the best position to judge when you need another dose to support you through the next few hours.

A number of my patients enjoy using their medication in this way.  On busy days, they may take their medicine each four to five hours.  On easier days, the first dose may last up to six hours, the second dose for the rest of the afternoon and, if they are not doing much in the evening, they may decide not to take the third dose.  This works well for them and preserves the usefulness of the medication over a longer period.

VARYING THE DOSE

Many patients also find that they can vary the dose taken a little to allow for variations in activity and stress levels.  For instance, you may normally take 50 mg three times daily.  On Tuesdays, however, you have a particularly busy day and experience some extra stress during business hours.  So, each Tuesday, you take 100 mg for your second dose just to give you that extra support during the stressful period. On the other hand, Saturday is a really easy day when you just potter around the garden, feeling peaceful. So you may only need 25 mg for the second dose and, maybe, the third dose also.

It works!  Many people with Parkinson’s disease have taken control of their medication and are using it in a way that best suits their individual needs.

L’dopa medication may be of assistance in relieving your Parkinson’s disease symptoms.  However, it will not slow the degeneration causing your symptoms, nor help you reverse your symptoms.  Make use of this medicine to give you the level of support you need to help you function in the most normal way possible, while utilising the lowest possible dose to preserve its usefulness over a longer period.

Always inform your doctor of any decisions you make about your medication. Many will support your right to make these decisions. If your doctor is not supportive, or becomes abusive (and, unfortunately, some are abusive), find another doctor. There are wonderful supportive and understanding General Practitioners and neurologists around; it is up to us to find them.

Beyond

There is strength in silence

There is strength in patience

There is strength in wisdom

There is strength in peace

There is strength in unconditional love

There is strength in going beyond the convention and resisting the temptation to blindly follow what they say you must do

There is strength in following your heart and the guidance of God for what you know is true

There is strength in all these things for they are the very things that bond us to one another and set us free

And with them there is great strength in you and me

Jill Marjama-Lyons, M.D. – Neurologist, Florida, USA

References

• MIMS Annual 2018: published MIMS Australia, St. Leonards, NSW, Australia. (MIMS is a major Australian drug reference guide available to all health practitioners)

• MARJAMA-LYONS Jill, M.D.; “What Your Doctor May Not Tell You About Parkinson’s Disease”;  Warner Books, New York, USA; 2003

• COLEMAN John ND; “Stop Parkin’ and Start Livin’ – reversing the symptoms of Parkinson’s disease”; Michelle Anderson Publishing, Melbourne, Australia, 2005.