Starting Parkinson’s drugs—research explained
There are no hard and fast rules when it comes to starting medication for Parkinson’s. So, in this blog, we explore some of the frequently asked questions and round-up the current evidence behind the answers.
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Quick summary if you’re in hurry
- Are very effective for controlling the main movement symptoms and can also be helpful for some of the non-movement symptoms.
- Can have side effects — both in the shorter and longer term. Not everyone will experience severe problems, and medication can usually be adjusted to minimise them.
- Do not suddenly ‘stop working’, but it becomes more challenging to manage symptoms and minimise side effects as the condition progresses.
But we still don’t know for sure…
- Whether Parkinson’s drugs have any effect — positive, negative or neutral — on the underlying rate of the progression of Parkinson’s.
- If any particular type of medication is ‘best’ in the initial stages or in the long term.
A quick introduction to Parkinson’s drugs
Symptoms appear when dopamine levels — a chemical messenger in your brain — become too low in the part of the brain responsible for controlling movement.
This is because dopamine producing brain cells have been damaged or lost.
As dopamine levels in your brain fall, movement slows down and becomes harder to coordinate leading to symptoms like slowness, stiffness and tremor.
Most drug treatments for Parkinson’s aim restore dopamine levels by:
- increasing the amount of dopamine in the brain
- acting as a substitute for dopamine by stimulating the parts of the brain where dopamine works, or
- blocking the action of other factors (enzymes) that break down dopamine
There are many things to consider when deciding to start taking medication, so in this blog we take a look at five of the most commonly discussed issues on the Parkinson’s UK forum and look at the emerging research evidence.
1. Controlling symptoms
“Will the meds make me feel better. Less tremor, less stiff and less tired?”
Since the first trials using levodopa in the early 1960s, the research evidence has shown that boosting dopamine levels in the brain is effective for improving movement symptoms including tremor, stiffness and slowness.
Today there is a range of medication available for Parkinson’s and there is good research evidence to show that for most people, these treatments are helpful for improving symptoms — particularly in the earlier stages of the condition.
More recently, research has suggested that Parkinson’s medications may also be helpful for improving some of the other (non-movement) symptoms including depression, anxiety, sleep difficulties and others.
However, many symptoms which are unresponsive to dopamine-based drug therapies and much more research is needed to develop better approaches to managing these other symptoms.
Take home message: The research evidence shows that medication is very effective for controlling movement symptoms and may also be helpful for some of the non-movement symptoms.
2. Side effects
“At the moment I have chosen to not take meds as I think my fear of the possible side effects is out weighing the inconvenience of the tremors and discomfort.”
According to a study published in 2014 the most common reason people with Parkinson’s are reluctant to start medication is fear of side effects. Two that people worry about most are dyskinesia and impulsive and compulsive behaviours.
Dyskinesias are involuntary muscle movements that can’t be controlled, including twitches, jerks, twisting or writhing movements, and restlessness.
- Research shows that around half (40 to 50 per cent) of all people with Parkinson’s will experience them after five years of taking levodopa.
- A review of 29 trials shows that dyskinesias are less common with dopamine agonists than with levodopa but other side effects (including dizziness, constipation and hallucinations) are more common.
- Researchers are developing new treatments that aim to reduce and prevent dyskinesias.
As well as helping to control movement, balance and walking, dopamine also plays a big role in the part of the brain that controls reward and motivation.
Impulsive and compulsive disorders are harmful activities that are driven or motivated by an instant reward, including gambling, hypersexuality, compulsive shopping or eating.
- The largest study conducted to date found impulsive or compulsive disorders in 13.6% of people with Parkinson’s - which is 2–3 times higher than the general population.
- The study also found they were more common in individuals treated with a dopamine agonist than in those on other Parkinson’s medications.
- Several studies have shown that impulsive and compulsive behaviours are more common in those who are diagnosed at an early age.
- Read more in our blog: Impulsive behaviour — too much of a good thing?
Dyskinesias and impulsive and compulsive behaviours, may arise in part because parts of the brain that are unaffected in the condition are overstimulated by dopamine therapy. So in both cases, reviewing and adjusting medication can be one of the most effective approaches for controlling them.
Take home message: Parkinson’s drugs can have side effects which can be serious. Not everyone will experience severe problems, and medication can be adjusted to minimise them.
3. Long-term effectiveness
“I’ve heard levodopa only has a life span of 5–10 years then it stops working…”
For a long time, the prevailing view was that Parkinson’s medications have a limited period for which they are effective, sometimes referred to as the ‘honeymoon’ period.
However, research has shown that dopamine-based therapies, and in particular levodopa, continue to be very important throughout the course of Parkinson’s. But as the underlying condition progresses, it becomes more challenging to maintain dopamine levels in the brain in the ‘sweet spot’ where there is enough dopamine to relieve symptoms but not too much so it causes side effects. And walking this tightrope becomes more complicated.
Most people who live with Parkinson’s and take medication will at some stage start to experience motor fluctuations — periods of the day when medication doesn’t work properly and symptoms worsen (off times), which alternate with periods of good control (on time).
The good news is that in recent years there has been a lot of research to develop new forms of Parkinson’s medications that provide longer acting effects and help to reduce ‘off times’.
More than 50% in the general Parkinson’s disease population develop motor complications within 5 years of diagnosis. However, they remain mild in the vast majority and are reversible in a substantial proportion of patients.
Take home message: Parkinson’s medication does not suddenly ‘stop working’, but it does become more challenging to control symptoms and minimise side effects over time.
4. Effect on Parkinson’s progression
“Do you think starting the meds accelerates Parkinson’s? I’m in two minds…”
There has been a longstanding concern that levodopa — the main drug used to treat Parkinson’s — might be toxic and actually contribute to the damage and loss of dopamine-producing brain cells.
- In the 1990s, research using brain cells grown in the lab suggested that levodopa may generate toxic chemicals called ‘free radicals’ and increase a damaging process called ‘oxidative stress’ inside brain cells.
- However, experiments in animal models of Parkinson’s suggested levodopa is not toxic in animals and may even have beneficial effects in helping damaged cells to recover.
- The most comprehensive study carried out in people so far found that levodopa does not slow the progression of Parkinson’s but does have a long- lasting beneficial effect on symptoms.
- There is currently another major clinical trial underway — the LEAP study — which aims to understand whether early treatment with levodopa is beneficial.
Take home message: Despite many research studies in cells, animals and people, we still don’t know whether Parkinson’s drugs have an effect — positive, negative or neutral — on the underlying rate of the progression of Parkinson’s.
5. What to start with?
“There seems to be quite a number of different medications that are used... I guess it’s a case of ‘suck it and see’. It just seems to be whatever suits you best as an individual?”
There is now a range of different Parkinson’s medications to choose from, but what does research suggest is best to start on?
In an attempt to answer this question, a large UK study called PD MED compared the effectiveness of the 3 main types of medication — levodopa, dopamine agonists and monoamine oxidase type B inhibitors (MAOBI) — in 1620 people.
The initial results (published in 2014) showed that after 3 years, levodopa had slight benefits in terms of symptom control and quality of life compared to the other two, and there was no meaningful difference between MAOBI and dopamine agonists.
This important study will continue to follow the progress of participants up until the end of 2019 so that we can understand the longer term effects of these different drug treatments.
Take home message: The best comparative study suggests that there is not much to choose between the different classes of Parkinson’s medication in terms of symptom control and quality of life in the early stages. We still need better evidence on longer term effectiveness.
Further information and support
If you have further questions, there’s more information available on the Parkinson’s UK website.
This blog is not meant as health advice. You should always consult a qualified health professional or specialist before making any changes to your medications or lifestyle.
