Parkinson's disease

Dopamine receptor agonists: medication for Parkinson’s disease

The main alternatives to levodopa in treating Parkinson’s disease are the dopamine receptor agonists (dopamine agonists). These drugs act directly on the dopamine receptors in the brain, taking the place of the dopamine which the brain cells can no longer produce. They may be used alone or together with levodopa. When used alone, the overall improvement in motor performance is usually less than when combined with levodopa.

Dopamine agonists have the advantage of causing fewer long term motor complications. When they are used together with levodopa, less levodopa is needed which also diminishes the risk of developing side effects, particularly dyskinesia. Dyskinesia is the name given to involuntary movements that can mean that people's bodies distort or their arms or legs jerk uncontrollably. In the past, dyskinesia was almost inevitable after prolonged use of levodopa. 'On/off' effects are much less marked with the dopamine agonists than with levodopa so that symptoms are less likely to appear if a dose is taken a bit late.
 
A range of dopamine agonists are available and most come as tablets or capsules of various strengths, although some come as patches or injections. People may need to experiment with their doctor to find what works best for them. Patches are handy for some people, but Kevin found the dose from a patch was not enough for him. Brian found it helpful to have his injection delivered by a pump, to help keep a stable level of the drug in his system. He could give himself a booster dose if he needed a bit more to help get him through an event e.g. a party.
 
The dopamine agonists are not without their own side effects, both in the short and long term, so their use must be carefully monitored.
 
Since the introduction of dopamine agonists it has been commonly (though not universally) believed that it was wise to start medication with this group of drugs in order to delay the use of levodopa as long as possible. Using a dopamine agonist might not control symptoms quite so well as levodopa, but many neurologists preder to use it as the first treatment in the early stages, particularly for people with young-onset Parkinson’s disease in whom prolonged use of levodopa might result in dyskinesia later.

Geraldine was on ropinirole for five years. She was aware this was not always the first drug to be chosen.

Geraldine was on ropinirole for five years. She was aware this was not always the first drug to be chosen.

Age at interview: 60
Sex: Female
Age at diagnosis: 42
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For the first five years of having it I only took Ropinirole which is a Dopa agonist as most people who have the disease know. It is thought, the school of thought that my consultant came from, that if you can stay off taking the Sinemet, (Levodopa) as long as possible then it’s the best thing to do. Others say get in there straight away because it builds it up. You know, you pays your money and you takes your choice, no one really knows. So I had to believe what my doctor told me and I did did manage on Sinemet or Ropinirole or requip as it’s trade name for five years and I took the brand new job.
Dopamine agonists should be introduced gradually, starting with very tiny doses and building up to an effective dose over weeks or even months. People did not notice the sudden and amazing effects observed on first taking levodopa (see Levodopa). The PD symptoms did not improve immediately and often side effects such as nausea and excessive daytime sleepiness were distressing.

Kevin's symptoms improved so much after 3 months that he began to doubt that he had PD and stopped the medication. 2 years later he needs larger doses.

Kevin's symptoms improved so much after 3 months that he began to doubt that he had PD and stopped the medication. 2 years later he needs larger doses.

Age at interview: 58
Sex: Male
Age at diagnosis: 56
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I started off on pramipexole, which is a Dopamine agonist and I’ve found it hard to get over the sick feeling from the drugs and I felt really sick. So that was changed to Ropinirole. Requip is the commercial name, and I, I stayed with them for about three or four months and got up to four milligrams, five milligrams. And I, I decided that although a lot of symptoms disappeared I was starting to, because I think because I felt better, I was starting to question whether I was ill in the first place. So I decided to stop taking the drugs, and slowly and gradually a lot of the symptoms started creeping back in, especially this feeling of slowness. It’s like you’re in slow motion. So I decided that I had to go back onto drugs again. This is, in the meantime I’ve been seeing the neurologist quite, quite regularly, every few months. I didn’t just do it off my own back, obviously. And we decided to try patches and I think that’s a drug called Rotigitine. Very expensive, they don’t normally like giving them out I don’t think. But I requested the patches and I tried the patches and they were really good. But you can only take up to about eight milligrams a day. They’re 24 hour patches but I felt that, I felt they weren’t strong enough. I could go one step further.

 

But although they go up to sixty milligrams for use with, in conjunction with other drugs, on its own, the patches, the Rotigotine, you can only take up to eight milligrams. So in conjunction with the neurologist again, we decided to put me back on to Ropinirole which is where I was about a year ago. I’m currently on five milligrams of Ropinirole, Requip. It’s not a hundred percent, it’s not perfect but, they eradicate a, a lot of the symptoms. I feel a lot better. Still got problems with my handwriting and the rhythm of cleaning the teeth.

Natalia experienced 6 weeks of depression when she went on pramipexole (Mirapexin) but eventually felt benefits from it.

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Natalia experienced 6 weeks of depression when she went on pramipexole (Mirapexin) but eventually felt benefits from it.

Age at interview: 63
Sex: Female
Age at diagnosis: 55
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He put me on Mirapexin and you start off with minute doses. And it was absolutely awful when I started, because I started getting side effects, which I hadn’t had before, sort of twitches and whatnot. And I think it, I can’t remember now, but I think it’s something like six weeks until you get up to the full dose. And those were awful six weeks. I think I took a month off work actually. I can’t remember very well. It’s funny how the, your mind seems to shut down on unpleasant things, I’ve noticed. But I just used to sit, I was very depressed. I thought I would never get depressed because I’ve got various reserves. And I know that with Parkinson’s you can get depression. I thought I never would, but for, for one month I was extremely depressed. And I’d just come down, get dressed, come downstairs, sit in the sitting room, not be able to read the paper, not be able to look at television. I’d just sit all day. And I didn’t even want people to come and see me, because I felt I had nothing to talk about except myself, which was very boring. But anyway that lasted for a month, I think until the medicine started kicking in and I started feeling more normal. And it has made me feel much, much better. It has helped me, helped me carry on with my normal life.

Ann appreciates the need to keep the dose of pramipexole as low as possible but it has had to be increased over time.

Ann appreciates the need to keep the dose of pramipexole as low as possible but it has had to be increased over time.

Age at interview: 68
Sex: Male
Age at diagnosis: 66
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What I’m unsure about in the medication is that I don’t want to increase too much. I’ve got it in the back of my mind that I need to go up slowly. And when I realised a few months ago that I needed to increase the medication, I went up, with the doctor’s agreement, to the smallest possible increase. But then three months later I needed another small increase. And now another two months later, I feel that I still need another increase. And I, I’m going to see the consultant this week and hope that she will increase it and talk me through what medication I ought to be on.

 

What difference do you notice when you increase it?

 

My hands are able to move, my right hand particularly is able to move more freely. Simple things like ironing or washing the floor, the right hand doesn’t work sometimes. Holding a knife, trying to chop things, it doesn’t work, it hasn’t got the strength in it now. When I go out walking I seem to fall over my feet a bit. I used to be a, a big walker. I’m not walking as much as I should, not as much as I used to, and I think I ought to make more effort to get out and walk more. But the medication makes me, stops me having all these feelings, especially in my hands. It’s a very difficult thing to explain why you need more medication. Just suddenly things aren’t working as well as they ought to.
The main reason for keeping the dose of medication as low as possible is that the higher the dose, the greater the side effects. Nausea is common and can usually be counteracted with a drug called domperidone. Brian found that since he has been on apomorphine he sometimes vomits unexpectedly without feeling nausea. For more information on apomorphine see Parkinson’s UK.

Fiona's husband could not tolerate the nausea when he was on ropinirole.

Fiona's husband could not tolerate the nausea when he was on ropinirole.

Age at interview: 46
Sex: Female
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The consultant did prescribe Ropinirole and, it hasn’t suited my husband, as he started taking it he got extreme nausea with it and our GP’s been fantastic very good he did prescribe something to combat that, but it still didn’t help and unfortunately, after some time it, he wasn’t feeling any benefit our GP said to reduce the dose and come off that and they would try something else. But, but unfortunately as my husband’s done that his symptoms have got worse, his co-ordination, his balance, he’s very stiff, and he just, so we’re just waiting at the moment to go back to the consultant to look at his medication and start trying something else.
Sleepiness is the other symptom which most of the people taking dopamine agonists mention. Some people complained of feeling generally sleepy most of the time though not necessarily falling asleep. Angela was once prescribed too high a dose of ropinirole and said it turned her into a ‘zombie’. Back on a lower dose she still found herself falling asleep in the theatre if she went out in the evening. Others said they would fall asleep suddenly and unexpectedly.

If the dose of Mirapexin pramipexole was too high Humphrey felt that it would be dangerous to drive because of falling asleep.

If the dose of Mirapexin pramipexole was too high Humphrey felt that it would be dangerous to drive because of falling asleep.

Age at interview: 57
Sex: Male
Age at diagnosis: 54
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I take three of those a day, one just, you know, the last one I take last thing at night as a sort of sleeping pill. If I forget to take it then I do notice the difference, I sleep better after it definitely. I take care not to take it before driving because it’s fairly quick acting and fairly soporific. And when I was on a larger, I’ve gone down on the dose, I’ve reduced the dose of this because, with my consultant’s permission, when I was on a larger dose I was falling asleep at the wheel of the car. And falling asleep in this sort of situation, I would have been [snore] off, you know, I mean I was literally falling asleep while, while talking to people and hearing myself talk rubbish. Microsleeps. They, microsleeps are, are, are a hazard. Yes, I do get them a little bit, a little bit now, not much, but I would say they were the only unwanted side effect that I get. The rest is fine.

John had made a record of his feelings about Ropinirole which had been added to the Sinemet he was taking initially.

John had made a record of his feelings about Ropinirole which had been added to the Sinemet he was taking initially.

Age at interview: 75
Sex: Male
Age at diagnosis: 67
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John' And then November a year later. November 2005, a new prescription was imposed, prescribed Ropinirole. I seem to remember saying that it didn’t make much difference if any.

 

Julie' It made you sleepy.

 

John' Oh, sleepiness, you’re quite right. So that brings us to the 27th February of ‘06. We have no comment there have we. Oh yes I have a little essay or set of points by myself headed, ‘Conditions changed since increasing Ropinirole dosage’. Firstly very noticeable increase in sleepiness, especially when in front of television. This is a comment on the programmes we get. This is a new phenomenon. Similarly when reading at any time which is absolutely abnormal for me. I always read in bed to all hours. But now I can do about three quarters of an hour. Increasing dizziness, especially when I get out of bed in the morning. This did not happen before taking the larger doses of Ropinirole. Walking is not as unsteady as it used to be. Of course the notes about the effect of Ropinirole mentioned account of the above symptoms, but why should we put up with them? What beneficial effects of Ropinirole, if any? Do we need such large doses? 9 mgs a day? I would be more comfortable on 4 mgs maximum. But actually nowadays I do take three times three millgrammes.

Philip can predict when he will need to sleep after each dose of pramipexole and can arrange his life to fit in with this.

Philip can predict when he will need to sleep after each dose of pramipexole and can arrange his life to fit in with this.

Age at interview: 58
Sex: Male
Age at diagnosis: 54
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Yes. I try to take the pills, because I know which pill does it. Exactly which pill does the damage. So what I try to do is some work first thing in the morning. Then at about 10 o’clock I take a pill and I go and try to do something but almost invariably you know… fully or flat out. But it only lasts about an hour. And again I do it in the evening because I have to take this particular pill three times. I do it in the evening. Again having tried to do something during course of the day constructive. And you feel very much better knowing perfectly well that you are going to take the pill and you are going to zonk out for an hour or around an hour. Then of course it’s brilliant at night. You take the pill and then you go to sleep.
Some people found that although their dopamine agonist made them sleepy they also suffered insomnia at night; several people described waking around 4am, often hungry and restless, sometimes using the time to catch up on work on their computer.
 
One group of dopamine agonists (cabergoline and pergolide) are derived from ergot and have been associated with fibrotic (scarring) reactions affecting the lungs and the heart. These drugs are still occasionally used but require careful monitoring. Andrew who had two Deep Brain Stimulation operations and was still having severe problems with walking and talking was put on cabergoline 7 years ago; it has helped him and he has had no problems with it.

Brian was put on pergolide by a GP who was not aware that he had had rheumatic fever as a child.

Brian was put on pergolide by a GP who was not aware that he had had rheumatic fever as a child.

Age at interview: 77
Sex: Male
Age at diagnosis: 63
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After a time one needs more than the Co-beneldopa or Madopar which I was taking. And it was suggested by these specialist that I should take one of three drugs in end and I went to see my doctor to choose one of them and my doctor wasn’t there. I had a locum, he didn’t really know my history. And he chose Pergolide mesilate in quite a large dose. Well it was wonderful, it loosened me up. The only thing was, I couldn’t go to sleep really, I’ve had difficulty going to sleep and that my, my voice as you can tell became rather soft. And lacked resonance.

 

But after two or three years of this, my, my heart started to misbehave a little. It, it would miss beats, or beat irregularly. I’d had rheumatic fever as a boy and during that time when I was in bed for five months I, could hear every beat of my heart without taking my pulse. It was a very disturbing experience. And some, something came back, my heart would miss a beat, and then jump, trying to catch up with itself. Then it was decided that they’d better take me off the pergolide. I actually collapsed.
Very worrying, though rare, side effects of dopamine agonists appear as neuropsychiatric disturbances.

Bob had a psychotic reaction and had to be taken off his medication.

Bob had a psychotic reaction and had to be taken off his medication.

Age at interview: 55
Sex: Male
Age at diagnosis: 51
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Unfortunately, last year I was taking a certain type of medication to treat Parkinson’s. It’s what they call, it’s from a group of medicines called dopamine agonists and sometimes with Parkinson’s, medication has to be tried out to find out if you can cope with it in the right way, as with any condition. Unfortunately with dopamine agonists I did suffer, maybe based on what had happened before, but I suffered a psychotic reaction which was quite severe. And a few things happened, but I ended up having to, I had to go to hospital and I was I was in a ward, a special ward in hospital for five weeks being treated for the psychotic episode. During that time I actually came off Parkinsonian treatment completely and it would appear that the problem in my case was the fact that I didn’t actually get on with this group of, this group of medicines. So since that incident, I’ve now been prescribed a different type of medication which, which does work for me and it works quite well.

Alun finds his compulsive symptoms harder to explain than his Parkinson's but was relieved to find someone who had also experienced this.

Alun finds his compulsive symptoms harder to explain than his Parkinson's but was relieved to find someone who had also experienced this.

Age at interview: 58
Sex: Male
Age at diagnosis: 49
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So this last year’s been the hardest part?

 

Oh yes, undoubtedly, because of not just physical problems, but mental problems as well. Feeling depressed, feeling compelled to do things. Feeling low, it’s been very difficult. Because although people associate Parkinson’s with physical problems the mental problems are more difficult to deal with, because like you can rationalise why you’re walking along funnily. But thoughts that you have or compulsions that you have, you can’t understand where they’re coming from.

 

So it’s much more difficult to deal with and there’s not been much research or much help given to coping with these problems and it’s partially the drugs. Like I was a compulsive person anyway because I had the book of lists one, book of lists two. Book of lists three, book of lists four, and I bought every CD by Eric Clapton. And so I’ve always been a bit compulsive like that, but this has sort of magnified it in different areas.

 

I’ve spoken to my specialist about it, which was a bit embarrassing because there was a student pharmacist and a student doctor in the room at the same time. And I had to explain what the problem was. He suggested I come off some drugs but that has actually made me worse, not in the compulsive disorder but physically worse. The best person who gave me the most support was a friend who’s husband’s got Parkinson’s who went through the same problems that I’ve had, and she told me in great detail what had happened and I didn’t feel so bad after that. So it was somebody who had cared with somebody with Parkinson’s rather than somebody in the medical profession. Because somebody who cares for somebody with Parkinson’s sees it twenty-four seven, whereas doctors don’t.
All current information about dopamine agonists mentions possible side effects such as; hallucinations, confusion, pathological gambling, increased libido and hypersexuality as possible side effects. Some also mention other behavioural changes such as an increase in appetite or binge eating, and the urge to buy or shop. The possibility that one of these problems might occur is not regarded as a reason for avoiding these drugs, which are valuable in the long-term management of Parkinson’s disease. But they should not be forgotten. David who developed problems on two different dopamine agonists expressed concern that he himself had little insight into his problem at the time. Helen’s compulsive gambling had occurred while she was using rotigotine patches and disappeared as soon as she was changed back to Sinemet. Gina’s occurred when she was on ropinirole (see Mental disturbances: depression, hallucinations and compulsive behaviour). Parkinsons UK have more information about Parkinson’s drugs and impulsive and compulsive behaviour.

Last reviewed May 2017.
Last updated May 2017.

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