Medication for Parkinson’s disease: levodopa

Levodopa is a substance which can improve some of the difficulties with movement experienced by people who have Parkinson’s disease. Discovered in the 1960’s, levodopa is an amino acid which is converted in the brain to dopamine. Dopamine is one of several neuro-transmitters used by nerve cells in the brain and elsewhere in the body to send signals to each other.

People with Parkinson’s disease don’t produce enough dopamine. When it became possible to manufacture levodopa, remarkable improvements were observed in people with Parkinson’s disease. But it was also soon realised that the use of levodopa rather than dopamine over many years carried risks of severe and disabling side effects. Since the 1960s many advances have modified the effects of levodopa but it continues to be the main drug in the treatment of Parkinson’s disease.

Other drugs, called dopamine receptor agonists, mimic the effects of dopamine, and may also be used, either alone or in together with levodopa.
Levodopa is now combined with another drug, a dopa-decarboxylase inhibitor. This prevents levodopa being changed into dopamine before it reaches the brain and allows lower doses of levodopa to be used than if it was used on its own. This helps to reduce some of the unpleasant side effects such as nausea, vomiting and blood pressure changes which are common when blood levels of levodopa are high. Two dopa-decarboxylase inhibitor drugs are in common use; benserazide and carbidopa, and these combined with levodopa make co-beneldopa and co-careldopa. Levodopa is also combined with entacapone, a COMT inhibitor – see Other medications for Parkinson’s disease and how to manage medication.
Levodopa is sometimes used to diagnose Parkinson’s disease when the cause of symptoms is uncertain. A patient is given levodopa and, if a noticeable improvement occurs, this confirms the diagnosis.

Helens tremor was investigated for three years before a trial of levodopa confirmed the…

Age at interview 39

Gender Female

Age at diagnosis 33

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I think after about two years or three years they did try me on Sinemet and it did stop which was one of the things they thought, Oh, maybe it is thatAnd then they offered me another brain scan just to see if the dopamine was present in the brain and it wasn’t or it was very limited so that’s pretty much when they decided that’s probably what it was.But and I don’t think you can ever be told categorically you’ve got it can you.I just think the medication works to take your symptoms away so then they assume perhaps that’s what it is.

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When Tom was put on levodopa he thought it wonderful because his symptoms went away. He didn’t…

Age at interview 40

Gender Male

Age at diagnosis 27

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I first suspected there was something wrong when I was travelling and I was writing a postcard to a friend of mine in, in Australia whose name is Anthony Diecopolis. And, and I got to the Anthony Diec and I couldn’t finish the opolis. And it’s very strange my hand had sort of gone into a sort of spasm and it just wouldn’t, wouldn’t finish writing the, the word. And so that’s a bit strange.

And so I went when, when I went to the doctor and said, What on earth’s going on And I had since then I’d also developed this slight tremor in my right hand. He said, Well it’s probably, a central tremor or trapped nerve or something like tha. And anyway, then it got a bit worse and then I was, I was recommended to go to a neurologist. And the neurologist had a look at me and gave me some pills. And he said, Come back and tell me if these wor.

This is about, about sort of, nine months after my, my not being able to finish the, the postcard. And, and he said, Take these pill. And the pills worked. Magically the tremors stopped and I thought this is wonderful. And so I went back to the neurologist and I said, Yes everything’s fine now. The pills have, the pills have worked And far from looking happy about this he looked rather, rather grave and he said, I think you’d better go to another neurologist

And so I went to another neurologist and he said. He did loads of tests, you know, and doing all this, and the usual things that become very natural to me now. All the sort of tapping the foot and banging the hands on the table and stuff. And, and he said, You have something that is within the, falls within the parameters of Parkinson’s diseas. And I thought, Parkinson’s disease, it can’t be Parkinson’s disease, that. And you know I’d associated Parkinson’s disease with elderly people as most people would and I was twenty-seven at the time.

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Several people whose symptoms were not seriously problematic when they were diagnosed could delay starting on medication for months, even years. The use of dopamine over many years can cause problems so these people understood that it was wise to delay taking medication, especially if they had been diagnosed with Parkinson’s disease when they were younger, and could expect to have many years of medication ahead of them.
Eighteen months after Rafa was diagnosed, his neurologist said he was glad he had not ‘condemned him to taking medication.’ When Joe was first diagnosed 17 years ago he was told it was sensible to delay starting medication. Later he understood that ‘Levodopa which is such a marvellous medicine, brings with it, after years of use, its own problems’ but he thinks this wasn’t made clear to him at the time.

David explains why he was not put on levodopa at first.

Age at interview 54

Gender Male

Age at diagnosis 48

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Well, the levodopa which is undoubtedly the best drug for symptom control but not necessarily the best drug for each individual simply because it’s believed at the moment that levodopa may have a have a limited life as it were in individuals. And that and that and it’s best to leave it until absolutely necessary before you start using levodopa. it’s possible that each individual may only have something between five and say fifteen years until levodopa stops working for them. But there’s some debate as to whether that’s actually the case or not or whether it’s quite a complicated issue. It may be because people don’t get put on to levodopa until they’re older and therefore are getting towards the end of the Parkinson’s regime as it were. But for people like me who are younger may have twenty or thirty years to go yet. It might not actually be the case that levodopa runs out but anyway it’s believed that that’s the that may be the case that the effectiveness runs out. So they tend not to use it unless it’s necessary.

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Some people experienced sensational improvements when they began to use levodopa. When Brian was put on Madopar he found that his life was almost back to normal, he could write and drive and walk. Three years later it was no longer controlling his symptoms and a dopamine agonist was added. Rachel noticed immediate improvement when she was put on Madopar 6 years ago, when she was 70, and she has remained on this, with only minor increases in her requirements and without any problems.

Humphrey was not given levodopa at first. When he was, Mari noticed a surprising improvement in…

Age at interview 60

Gender Female

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I think because he got it so young, and because he himself knew that the benefit of keeping as slowly as possible your progress through that ladder of drugs. I think he left it quite a long time in each case before he moved on. And so we did see quite a lot of loss in each stage and then the drug would come in and make you quite perky for a bit but then, of course, you lose the effects of the drug. And actually I think one of the things about being finally put on to dopamine was it almost made him too perky. I think it would have been sensible to warn him not to stretch muscles and tendons that he hadn’t been using properly for a long time. And it, you know, he had some trouble with the leg because he’d said, Oh whoopee. I can, you know, run for trains again Or something stupid but that’s the sort of person he was. So I think that that is one of one of the issues that we half understood. it’s easier to understand it with hindsight.

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Geraldine had been on a dopamine agonist for 7 years but as her symptoms got worse she agreed to…

Age at interview 60

Gender Female

Age at diagnosis 42

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I said to the doctor, he never pushed me, but I said, I think it’s time I took levodopa because I’m not coping on this And I started on levodopa I can remember it was at Easter and I took a week of it and suddenly this hand which had been increasingly becoming like a crabs claw like that, then I used to walk with a limp and my hand was bent like this all the time suddenly started moving. I remember thinking, My hands are moving, you know Now this was the levodopa and it just sort of released my body from what felt like a tighter and tighter and tighter constriction. It felt like my body was shutting in on me without the levodopa at that stage. But unfortunately the feeling didn’t last very long. And I thought, I’m going feel better. I’m going to be better Unfortunately, you’re never going to be better but the levodopa worked pretty instantly with me and I was fine.

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Jean has been on Sinemet since her diagnosis 8 years ago. The rocket which helps her so well is…

Age at interview 72

Gender Female

Age at diagnosis 64

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Well, when I first started taking the tablets it was very good for me really. Because from I couldn’t sort of, couldn’t pick up say that vest, I couldn’t pick that up and fold it, I couldn’t do that. In actual fact it’s just starting to go again. So that’s after all them years. So I’ve got to say after ten years this has just crept back in. So I, when I see him he’ll probably change me tablets. And it was like you’d been born again. That was the feeling you got. It was so nice that you could sort of go upstairs, come down and you could walk out. But you, as I say you can’t walk far because of the muscles. Then, they, they sort of do hurt you. But once I take them tablets, my husband calls them the rocket, once I take the rocket they work wonders.

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Not everybody reacted favourably to levodopa. Several people mentioned nausea, giddiness, constipation, suddenly falling asleep. Angela started on Sinemet as part of a trial of four different treatments, but her blood pressure fell and she felt disorientated, faint and excessively sleepy during the day, so she asked to be taken off it after a week.

Eddie developed breathing problems and was sure they were caused by the Sinemet he was taking, so…

Age at interview 83

Gender Male

Age at diagnosis 80

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I can’t remember exactly when the walking became affected. The doctor at the hospital was conscious of the fact that my walking wasn’t as good as it should be and he noticed it more than I did to start with. And the effect of the Sinemet plus, I think it was, the effect of that was it improved my walking and also my hand wasn’t shaking so much, so it was being effective. So in the first time it didn’t consciously affect my breathing but he wanted he wanted to increase the dosage because he didn’t think the dosage was strong enough to do the job properly so I had to take an extra tablet, sixty two point five. And when I started taking that that’s when I started suffering from the breathing problem.

Can you describe the breathing problem?

Yes, I would wake up in the night and you breathe through your nose normally and I reached the situation where breathing through my nose was very difficult and the worst thing I could do was sneeze because it increases the blood pressure and so I got the feeling with my nose being blocked up and the effect the effect was very unpleasant.

And so what was the next thing you do you did? You told I think you told me you went back to the doctor.

I stopped taking the Sinemet and.

Had the doctor told you that it was definitely caused by the Sinemet?

I had a after I went back to the hospital, the second appointment, but he didn’t seem too concerned about the breathing effect he was more concerned about the effect by not taking the Sinemet and doing harm to myself and so he suggested I should go back and have a second try. So I thought, Well, with respect to the medical profession the doctor I’m prepared to do that So I went back and I had and I had a second go but the effect was worse than the first time so I wrote a letter to the local doctor saying that I was I wasn’t prepared to to put up with horrific breathing problems. I would rather put up with the problem with my hand shaking than the breathing so he wrote me a letter back saying that he respected my viewpoint which I which I had a right to choose for myself.

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Some people who had been most impressed by the initial improvement after taking Sinemet were several years later having trouble with its side effects and by the reappearance of symptoms as each dose wore off. Geraldine believed that this was because her brain no longer produced any dopamine. So that if the dose she had taken wore off, there was no longer any ‘dopamine buffer’ to carry her through till the next dose reached the brain. Sinemet SR (slow release), which Geraldine takes at night is a ‘magic bullet’ protecting her from the crises she used to experience when her dopamine levels fell during the night.
Geraldine is extremely sensitive to Sinemet. She can get a huge ‘hit’ in an emergency from dissolving a tablet in water. ‘It feels like a great rush of hot fizzy fluid. It always goes to my outer extremities. I don’t think I have very good circulation and it sort of zings straight into my fingertips and my toes and they almost feel on fire. And I get very hot. I have big, huge sweat runs off me and I don’t sweat easily as a person normally. And it feels very like butterflies in your stomach, you know, that apprehension before you go on the stage to do something, that kind of thing. Excited almost, stimulated.’
Managing dopamine levels is very complicated. Some people find that when they take levodopa close to meals, especially meals containing protein, the desired levels are not reached – its ability to get into the blood is blocked.

For many years Geraldine found that finding a time when she could safely eat was almost impossible.

Age at interview 60

Gender Female

Age at diagnosis 42

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Doesn’t happen for everyone but it did for me, protein attacks levodopa. And if you don’t get your eating schedules right you in fact can undermine the effects of the drug totally. So for me it’s very complex where I am now because I I’m eighteen years into the disease. I’m actually better. I look better than I did at the beginning because I have learned how to manage the medication. But it’s very difficult because I take medication every two hours and I’m not supposed to eat for an hour before I take the medication or half an hour after I eat – take the medication dication. So that leaves me a one half hour eating slot every two hours. So you having a normal meals is not possible. I have to sort of graze my way through the day and that again has social implications because in my job, I worked for the government, I had to do a lot of social speaking and going to dinners and things. And, you know, I could never eat the food and I always was the one that was different.

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For Geraldine, Tom and David, large doses of dopamine produce unpleasant side effects which got worse over the years. To avoid these effects they needed to take smaller doses, but such doses tend not to help for more than 90-120 minutes, so they increasingly shorten the intervals between doses.

David develops dystonia if his levodopa levels are too high.

Age at interview 54

Gender Male

Age at diagnosis 48

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I do have some dystonia now butfor me fortunately at the moment it’s only in my feet now.I can’t move my toes without them being on the floor.

Loaded up I can’t just freely just put my feet up and twiddle my toes backwards and forwards otherwise my muscles go into spasm and my toes curl up and that’s a sort of dystonia, you know, where the muscles contract uncontrollably.So it’s not a big problem for me.I just avoid twiddling my toes I know it sounds silly.But something like when you wake up in the morning you lie in bed and stretch and you stretch all your muscles.I can’t do that with my feet.I can’t allow my feet to stretch uncontrollably otherwise the muscles will just go into spasm and my toes will either curl right up or go right down.

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He uses pill boxes with alarms on them to be sure to take his medication on time. This way he…

Age at interview 54

Gender Male

Age at diagnosis 48

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I think one of the reasons I’m successful at controlling my symptoms with this tablet is because I’m very strict about my drug regime. I take the tablets at exactly the right time, not five minutes later not five minutes earlier, at exactly the right time. I have two little pill boxes that have an alarm on them. One that is small enough to carry in my pocket outside and one that I use in the house. When it peeps, I take the tablet. Not a minute later, not a minute before. And I think just keeping a rigid control over the dose level helps me a lot. Because I know, I’ve seen other people go, Oh oh, I’ve gone fifteen minutes over my time Or something, you know, and they’ve started to run down, then you’ve got to take a tablet, then you’ve got to wait while it starts to work again and so you’re going through all these like peaks and troughs. By being rigid about when you take your tablet it helps to smooth out all these peaks and troughs. And each individual finds their own best time. It may be two hours and fifteen minutes, maybe two and a half hours or maybe slightly less I say each individual over time will find out what’s the best works for them. And so I found I think that’s a very important part of the drug treatment is time and doses, and being careful about that.

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Tom goes through many states with each dose of levodopa. Moments later he realised he had…

Age at interview 40

Gender Male

Age at diagnosis 27

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The pink tablets were L-dopa [levodopa] which is the gold standard for treatment of Parkinson’s and is, is the thing which, which, allow me to, to talk to you now because without them I wouldn’t be able to move. In fact they’re making me move rather too much as you can see, but that’s just a side effect which comes about, usually about, after about four or five years of taking them, and it, I don’t have it all the time but this morning I have it. It usually comes about one, particularly when you’re being interviewed actually if you have a bit more adrenaline than usual then you get more dyskinesia so probably find that after this interview I, it’ll settle down again but it, it’s just any sort of stress or adrenaline or.

Is it quite uncomfortable for you?

Yeah, yeah probably, it is a, it is at the moment it’s [sighs], it’s not that uncomfortable it’s more that I’d rather not be doing it in front of the camera, and, you know, and it’s not very pleasant to be sort of, you know, and people watching this thinking oh look at him waving all around’ and, and knowing that people are thinking that and [laughs] it’s just not very nice, but it doesn’t bother me that much.

To what extent is it related to stress? And to what extent is it related to when you last took the L-dopa or how much?

Yes it is very much related to that, and usually the worse it gets, it’ll get worse at the end of the period of the dose so that it gets worse and then it’ll disappear completely, and then it’ll fade away into tremor if I didn’t take the next load, lot of pills, and then the tremor will get awful and then if I didn’t take any pills after that then I would eventually become frozen, so. So it’s almost like too much movement, normal movement, tremor, no movement.

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Most people with Parkinson’s are familiar with the concept of ‘on/off’, though not all describe what happens in the same way. In ‘Parkinson’s disease and problems with movement‘, Karen described bad days when for some reason her medication seemed not to work and everything is difficult, or when she has severe dyskinesia (involuntary movements that can mean that people’s bodies distort or their arms or legs jerk uncontrollably). On other days everything works well and she can do all she wants to do.

Neil used to keep a record of on and off times to tell the neurologist at his hospital appointment.

Age at interview 48

Gender Male

Age at diagnosis 35

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Good days are brilliant. I can do, well, touch wood, I’ve had this week, I think, I used to keep a diary before we go to hospital every half hour, was it good that half hour. And I’ve been keeping a secret diary the last week or so in what they call on’ when you’re good, and off when you’re bad. And I usually get up about 7 oclock. Go to bed about half-11, 12. So what’s that about 13,14 [hours], something like that. In all that time I was only off for about two hours, which is good. But then that was at night-time just before I was going to bed. So I used to sit down and watch telly and so, it’s good.

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If Sharon forgets to take her medication she soon goes off.

Age at interview 57

Gender Female

Age at diagnosis 49

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And there is a bit where if I can’t find my tablets in my handbag, instantly, because each, the tablets only cover four hours, at the end of that four hours the symptoms come back pretty fast. And so I’ve got to be able to get my tablets. So I’ve always got two or three people who are holding a few of my tablets so that I’ve, just to stop me panicking. And when I go away on holiday the first thing the girlfriend takes from me is a bottle of my tablets, so that I’ve got a bottle and she’s got a bottle. Because then I can relax.

So, at the end of the four hours, what starts happening?

I begin, at the end of the four hours, when the tablets start to wear off, I begin to ache, the muscles in my left shoulder begin to tense. My left hand starts to shake. My right knee starts to shake. My right leg starts to shake. My voice gets worse. I become unsteady. Sometimes, if I leave it for too long I can’t get the tablets out of the pod. I just give it to somebody and they know it’s one pink, one green. Otherwise there are tablets all over the floor. And that’s happened in more than one supermarket.

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Sometimes Geraldine will go off soon after a dose of Sinemet.

Age at interview 60

Gender Female

Age at diagnosis 42

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Sometimes when my medication isn’t working properly when I take my pill as I’ve just done five or ten minutes ago they knock me off rather than turn me on. So I was quite fluid I think when we started having lunch and now if you look my hand is it’s very hard for me to stop it shaking.

And it’s not Parkinsonian shaking, it’s a side effect of the medication that makes me ironically shake. And the bit of the half of me that’s not badly affected is now shaking too which it wouldn’t normally do so this seems a double whammy to me. And both stiff and shaky at the same time and my diaphragm is pulling me forward so my stomach bloats. And it means I just nearly choked on a piece of celery I was eating there because I can’t swallow without thinking about it. My voice goes very soft because I can’t volume control it. I can’t speak any louder than this now even if I wanted to. And my face feels very immobile and you know, trying to smile would be difficult. My eyelids sometimes get weighted down and I find it hard to open them again. And I have to think about everything I do so to try to get up, I’ll try to get up now and I can just about do it. But my balance is very – I won’t come too far, because I’m wired up to you. My balance is very unsteady and if I want to walk I can’t pick my feet up you see. I have to walk like this with little shuffly steps. And I was moving around quite normally wasn’t I ten minutes ago.

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Tom has days when he wakes up knowing that it will be a bad day, when the bout of exercise he does each morning on a rowing machine goes badly. But this is not the same as his ‘off’ periods. His ‘on’ periods are when his medication is just right, there is neither too much or too little levodopa circulating. He starts to go ‘off’ when the last dose of levodopa is running out. However his most dramatic symptoms may well occur after he has taken the next dose but before it has begun to kick in.

Toms offs are both dramatic and scary to anyone observing them though he knows he always comes…

Age at interview 40

Gender Male

Age at diagnosis 27

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Off and on are so unbelievably different they’re like sort of Jekyll and Hyde really, they’re, off is, my off can be so horrendous that I am unable to move, I’m totally unable to move, unable to move a single, and this is far worse than, than I would be at night. it’s, you know this can be this can be sort of well I. Unable to move a muscle and if I try and move a muscle I would, the tremor would be so awful that I would be literally flapping around like a, like you see those fish, you know, coming, coming out of the sea, you know, flapping around like that, you know, just awful, awful, awful. And, it’s, I mean it’s, I’m so used to it that it’s, it’s kind of, par for the course for me but when people see it for the first time, in fact I had someone interviewing me once who, who saw it and she, she wrote that she was about to call 999 but she was, she decided not to because I was kept on joking, making jokes about this so, so and actually I got asked on a plane once she, someone was, the stewardess went for my tongue because she thought I was having an epileptic fit, and that, that I mean it’s literally like, like being in an electric chair it’s kind of, you know, it’s that, it’s that violent.

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Several drugs introduced over the years can modify the fluctuations people experience with levodopa (see Other medications for Parkinson’s disease and how to manage medication).

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