The Epilim Scandal - Dr. Jim Morrow
Epilepsy Sparks Insights podcast transcript (listen to the audio podcast here).
PLEASE NOTE: Women and girls should not stop taking valproate without first discussing it with their doctor. What is written below or in the podcast is not medical advice.
Dr. Jim Morrow
Introduction
This week on the podcast we are talking about Sodium Valproate, aka Epilim, its feature in the UK Government's "Cumberlege Review", and why it has been called a "public health scandal" by some.
Sodium Valproate is a medicine commonly used to treat epilepsy (and bipolar actually) and has been around since the 1960s. It's a drug that I used to take years ago - but it didn't work for me personally.
You'll find it referred to mainly as Valproate in this podcast. I shall be talking with Dr. Jim Morrow, a former Neurologist from Ireland, with whom I did a live video interview a few weeks ago (check it out on my YouTube page if you haven't already!).
Welcome to the podcast Jim, tell us about yourself!
Meet Dr. Jim Morrow
My name is Jim Morrow, I have been a Consultant Neurologist, based in Belfast, I qualified back in the late 80s and got quite interested in neurology a few years later. I realised then that epilepsy was quite a “Cinderella” subject within neurology - yet it was probably one of the commonest diseases that neurologists should see. I say “should” see because they didn’t really see many people with epilepsy at that time. They tended to abrogate their care to general practice, General Physicians, etc.
So, I took myself off to Cardiff for 3 years and worked with Prof. Alan Richens who had set up one of the very first specialist epilepsy clinics in the UK. I was very impressed by the work there and I did a research project ( a doctorate) to compare the outcomes of patients with epilepsy who came to our specialist clinic against those patients that were seen - in fact by neurologists rather than GPs because neurologists at that time were probably the gold standard, though they weren’t specialists in epilepsy.
2. Access to a specialist Neurologist and an Epilepsy Nurse
JM: That research showed very clearly that the specialisation in epilepsy had big advantages for those patients. They had much better outcomes, many more became seizure-free, the use of drugs was better, there were far less side-effects. People felt generally more satisfied, they had more information to hand, etc.. So, I presented this work widely, and happily now I can say that this at least partially contributed to the fact that there are now very few areas within the UK that don’t have a specialist epilepsy clinic that people can access.
The only problem with the specialisation in epilepsy is that sometimes it’s quite difficult to “get in” to these clinics because they’re a victim of their own success. They have a large number of referrals and a small number of doctors to take those referrals. Happily, though, the specialist epilepsy clinics have evolved and now they have brought on board perhaps one of the best pieces of “equipment” (!) which is the specialist Epilepsy Nurse! These nurses are extremely well informed, they are extremely helpful, and much, much more accessible than our neurologists.
3. The importance of communication
TR: They (Epilepsy Nurses) don’t necessarily use long, “funny” words either! So they’re bilingual, right?!
JM: Are you implying that doctors don’t speak English properly?! :D We can speak a bit of Latin and a bit of Greek, you’re quite right.
TR: Yes, you’re multi-lingual!
JM: Yes, the trouble is, yes, we should speak English when we all too often speak medicine-language.
TR: Personally, every neurologist I’ve ever had has spoken my “language” but because I know that this is a really common issue - that many of us have (in understanding the “multi-syllable words” of that we aren’t familiar with); we created the Epilepsy Glossary; so that people can just see the translation.
JM: In my view, it (issues in communication from some neurologists) almost stem from the way in which we pick people to do medicine and become doctors. To get into medicine, you need (usually) A’s at A’Level in physics, chemistry, maths, and biology. I’m not sure those are the best subjects to make you a good communicator - which is what doctors have to be.
TR: Communication skills and empathy are valued much more nowadays.
JM: Well especially I think in neurology, where many of the diseases that we treat: we can’t cure! We can help and we can support and exactly as you say: empathy, communication, are far more important than the physical things that we can do for patients.
4. Awareness of epilepsy research
TR: I was going to say that that’s why that we as patients need to be much more aware of the amazing research that is going on out there, and how much we need more of it! Without research into new treatments, preventions, methods of care; we’re not going to get very far. Things take money. That’s how I think we can get more people into it (neurology). Would you agree?
JM: Oh, absolutely. Sometimes people don’t appreciate research because they’re looking at things that seem a bit obscure, or whatever, but as time goes on it can make a big impact on how we treat patients. Without research, we wouldn’t have many of the drugs that we have. Drugs have to go through various stages of research: to prove that in Phase 1 to see if they’re safe on animals, Phase 2 is really a short-term drug trial to show that they (the drugs) can actually have some effect, and Phase 3 is giving patients much longer doses of the drug so that you can see if the effect is maintained, but also any side-effects that come through - and that takes many years! But, it vitally important that we do that research otherwise we won’t see any new medications coming on the market. The same is true for other ways we treat patients as well. I think it’s incumbent upon us to prove that it (the drug) is actually beneficial.
TR: Now this leads me on to something else actually….
5. Epilim, the Cumberledge report, and the pregnancy register
TR: Some come on a lot later…and I think that you’ve got a story to tell us about that.
JM: Oh, absolutely. Sometimes people don’t appreciate research because they’re looking at things that seem a bit obscure, or whatever, but as Well yes. I mean, we are very good at picking up acute side effects, e.g. if a person takes a rash, or vomits after a drug, we pick that up very quickly, it’s fairly obvious, and doctors get to know about it because the GP will fill in what’s called a “Yellow Card”. A yellow card is linking a side-effect with a drug and the Committee on Safety of Medicines* put that together and then issue alerts that this drug is associated with this particular side effect. But, that’s only part of the story…
Drugs can have much longer-term effects and there’s been recent publicity about a review carried out by Baroness Cumberlege, looking at the longer-term effects of certain medicines. and medical devices. In particular: Vaginal Mesh, Primodos (which is a hormonal drug for pregnancy), and from our standpoint; looking at the longer-term effects of a drug called Sodium Valproate or Epilim - which is widely used in epilepsy.
I gave evidence to that report because a lot of what she presented in that report about epilim came from our work here in the UK.
It was called the UK & Ireland Epilepsy & Pregnancy Register. What got me interested was a lot of new anti-epileptic medications were coming on the market and they were being increasingly widely used because these drugs maybe caused less sedation, they had less other side effects, and they seemed to be effective for many people. But my question then arose: “Ok, I’ve got a young woman, I want to put her on this drug, she’s going to be on it for many years, what happens if she gets pregnant? Is it safe for that woman to take that drug during pregnancy? The drug companies came back and of course said “Oh, we know it’s safe, yeah, yeah, yeah” and I said “Well how do you know?” and they said, “Well, we test it on rats.”. And I thought, hmmm, ok, well that doesn’t really answer the question as far as I’m concerned!
So, we set up a research project, and it really wasn’t rocket science, it was a really, a very simple thing to do: we set up a register. Basically what we did was we asked GPs, neurologists, or the patients themselves; if they knew of a woman or they were the woman who got pregnant taking one of these drugs, or had epilepsy and in fact weren’t taking a drug at all; just let us know. And what we did was take the details of the drug that they were on and the dose, and then we asked that woman’s permission to contact her General Practitioner 3 months after the baby was born, just to find out if everything went alright or not, e.g. were there any problems with the baby, any problems during the birth, etc, and then later we worked with the University of Liverpool to actually follow the children up into the school-age years.
And it’s become quite a powerful tool. We’ve recruited women simply through a free-phone or we’ve got a website where you can download the forms, and what came out of it was: we had, as I say we’ve got very large numbers - we’ve got some 15,000 pregnancies in the register now, with 2-3,000 on most of the anti-epileptic drugs that are used, and that gives us a lot of good evidence.
And what came out for me was very reassuring at first, in that these new drugs that were coming on the market actually appeared to be safe in human pregnancies. But what really stuck out like a sore thumb, and really shocked me, was that one drug, sodium valproate (epilim) - which had been around since 1974**, really, as I said, stuck out like a sore thumb, because there were very many more major congenital malformations being associated with this drug. 10% of the children that were born had some kind of structural abnormality like spina bifida, cleft-palette, club foot. And when we followed them up, up to school-age, we found that up to 30% of the children, a third of the children exposed in-utero, during pregnancy, to this drug, had developmental delay, difficulty communicating with others, autism spectrum disorders and a third of these children seemed to be being affected by either structural abnormalities or these neurodevelopmental delay problems, and yet this drug had been around for 40/50 years, it was the second commonest drug used in the United Kingdom. So this drug, if you extrapolate, has clearly caused damage to many, many thousands of children over the years, and in fact, probably hundreds of thousands of times more children than Thalidomide ever did. It (thalidomide) was picked up very quickly because the abnormalities were unusual, whereas with valproate, were abnormalities that can occur, like spina bifida, cleft palate, For a doctor, you might have one woman who gets pregnant on valproate in your whole career, or if you’re a neurologist, maybe once every few years, so that once in a while a child will be born with spina bifida in your practice, but sure, that happens. We don’t necessarily relate it to the drug. And then, if a child has learning difficulties, it’s unlikely the school psychologist or whoever will relate it back to the drug that the woman took during pregnancy. So this is what Baroness Cumberlege was bringing to light: that there are these longer-term effects not only on the patient that takes the drug but on a potential baby that aren’t really being picked up by current monitoring systems.
TR: That’s a lot of people to be affected by something - and it’s not like catching a bug, it’s something that is going to be with that child for their lifetime.
In your opinion, how should the medical profession, the international as well as national bodies, and us as people affected by epilepsy: how should we react to this do you think?
JM: Well, I think that a high percentage of the medical profession, certainly those that specialise in epilepsy, are aware of this problem and have been aware of this problem for some years because I’ve been talking about it for a long time, presenting at international and national meetings, so they are aware, and nowadays, the flyer that comes with epilim does highlight that there is a potential risk here. But I think that Baroness Cumberlege herself has highlighted that this does suggest that there is a failure of the monitoring systems that we have to look at these long-term effects, and this needs to be addressed. We’ve offered ourselves to try and continue with our register and to help in any way we can. Our register though is a research project. It’s totally voluntary. Women do not have to register with us if they become pregnant. Because there’s a lot of interest in this, we do get about 30% of all UK pregnancies in women taking anti-epileptic drugs. But, if we got 100% we could get the answers for individual drugs for new drugs coming along much, much quicker, and maybe that is the way to go.
TR: Is it easy for people to connect with the person in charge of the study? How would one do this? And can you reassure us it’s not stressful as well?!
JM: Naw, it’s dead easy! The way is to connect is if you’re a woman who’s pregnant or if you have questions, we have a freephone - and you can look that up on our website which is www.epilepsyandpregnancy.co.uk (all one word). If you ring the freephone you will get through to a marvelous specialist epilepsy nurse called Beth Irwin, who has really run this register since its inception about 20 years ago, and she is probably the most knowledgeable specialist in epilepsy that exists and she’s also very approachable, very friendly, and I think that anybody who’s got any concerns would be delighted to talk to her and she will hopefully reassure them or be able to give advice or refer them on to somebody who can give them the appropriate advice.
TR: That’s wonderful that we have her to contact. What would you say to our listeners who aren’t from the UK; because we have a lot of people who are in the States, in Australia, in India, in countries in Africa, and lots of people don’t have access to epilepsy nurses, and they’re trying to learn more about epilepsy and the drugs - which are often even more limited than in other parts of the world. What should they do - to try and monitor their own health if they’re taking sodium valproate?
JM: Gosh, I don’t know the answer to that to be frank. In most developed countries they will probably be under a neurologist. But I agree with you, that in the developing world, yes, they may not have that access, the doctors may not always have the knowledge, and to get to see somebody may be quite difficult. Also, the range of drugs that people use will again be restricted.
Here in the UK there are people that say that we should not use Valproate - at all! and unfortunately, to my mind at least, it’s not going to happen. And the reason I say that is that I would prefer that we didn’t use valproate (particularly in young women), but for the foreseeable future, I think we’re going to have to. And the reason I say that is there are certain types of epilepsy for which Valproate is the only drug that works. And that leaves women with a stark choice: take this drug or have seizures.
TR: And seizures - depending upon the type that fancy raising their ugly heads - may have a more negative impact upon the mother and the unborn child, than the drug itself. But do you tell? We can’t, right?
JM: No. But what a woman needs to do is have her diagnosis reassessed. A lot of people with epilepsy grow out of it. Do they still need that drug? Or, do they have a different type of epilepsy (other than the ones that I’m talking about) in which valproate is not the only drug that works? And could we then change the drug to a safer one? So there are options. And even with valproate, there are options. What we find on our register is that the higher the dose of valproate, the greater the risk. So can we possibly reduce the dose? And another thing that came out - and I think that doctors perhaps aren’t so aware of this, is that if you combine valproate with other drugs like Lamotrigine, it does enable you to reduce the dose of valproate. Which again, reduces the risk to the baby. Now it’s kind of counterintuitive because if you talk to doctors they would prefer you to be on one drug rather than a combination, and particularly in pregnancy they’d prefer you to be on one drug rather than a combination, but there is this special circumstance where if that other drug allows you to reduce the dose of the valproate, then it may actually be a better thing to do than continue with the valproate at the higher dose.
TR: Also though, I guess we don’t know if that other drug will be useful or not, so…wouldn’t it be a bit trial-and-error-like?
JM: It will always be a bit of trial and error and if you start changing doses and adding things in, you may lose your driving license, so it has social, occupational, and other implications. So, it is not an easy decision for a woman to make. It’s an individual decision, you need to have somebody who is competent in advising and discussing these issues, like an epilepsy specialist nurse, or a neurologist.
TR: And we have an Epilepsy nurse organisation in the UK don’t we?
JM: Epilepsy Specialist Nurses Association.
TR: That’s it!
JM: And also, in Belfast, we set up one of the very first joint Epilepsy Obstetric clinics, so that I and my epilepsy specialist nurse Beth Irwin attended the obstetric clinics during the woman’s pregnancy, Becauseobstetricians mainly don’t have much of a clue about neurological disease in general (and epilepsy in particular), so we were there to advise them, but also to advise the women and make whatever adjustments needed to be made to the drugs. Because we talk about epilim - and a lot of women think that’s been highlighted so no epilepsy drug is safe, and in fact most of them, in fact, all of them are safe, except for valproate at the present time. There’s a question about Topirimate but it’s not resolved yet, but all the other drugs appear to be safe.
However, there are other things that happen that maybe obstetricians and GPs aren’t aware of such as Lamotrigine - and it’s safe in pregnancy, If you get pregnant on lamotrigine your blood levels of lamotrigine drop, so you could have seizure breakthrough. So that should be known about so that the dose of lamotrigine can be increased a little bit during pregnancy to counter that. It’s important to see someone who really knows about the subject and sees a lot of people with epilepsy.
6. Taking things forward
TR: What would be the recommendation for people who are interested in the Cumberlege report? How can they positively impact future decisions on sodium valproate?
JM: I think anybody with epilepsy needs to put pressure on their local MP to look at this report and to see what should be done in their area and what needs to be done is to provide sufficient numbers of neurologists, provide sufficient numbers of epilepsy specialist nurses, so that if the situation arises that a woman with epilepsy wants to become pregnant, they can get reassurance if they’re on one of the safe drugs, or options can be looked at it they’re on valproate.
I think that this is the time to do it because the report is out there. It’s been presented to government. And it’s a question of pushing them to do something about it, to implement this report and not just to say “well, sure but vaginal mesh and primoidos are sort of out and it’s just this other one with epilepsy. Sure we can take that on board but do little about it.”
TR: Now, we want to end on something positive (!), what drives you with your work?! Do tell! And what does your work involve now, because you’re not a full-time neurologist these days are you?
JM: No, I took early medical retirement, actually on medical grounds, because I ironically had a serious neurological condition myself which has left me with epilepsy! My colleagues actually had to look after me which was a bit scary! But I’m still very much involved in the work of the register and I’ve tried to amuse myself in other ways by writing crime fiction novels! Got a bit of neuroscience in it as well, which of course it has!
TR: Now if people want to find out more about you, where should they go?
JM: Get in contact with me through you!
7. Conclusion
TR: So, contact Jim through me it would appear! You can find me, Torie Robinson, through my website torierobinson.com, through epilepsysparks.com, or on Twitter, LinkedIn, Facebook, or Instagram.
I truly thank Dr. Jim Morrow for such a passionate talk and for educating so many of us regarding a drug that millions of us are taking.
Do know that sodium valproate is an effective anti-epileptic drug for many people but carries a significant risk for women having children. The drug is no longer prescribed to women of childbearing age unless they are on a Pregnancy Prevention Plan (PPP), due to the implementation of new guidelines based on recommendations from the European Medicines Agency.
If you have any questions regarding it, never just stop taking it (well, not unless you want to encourage a seizure… - NOT a great idea). As Jim Morrow said, for people with questions about epilim, contact your doctor, your epilepsy nurse, or your neurologist. Lots of other people are in a very similar boat to you!
I also sincerely thank Julia Cumberlege for the incredible length of time, energy, and passion invested in The Independent Medicines and Medical Devices Safety (First Do No Harm Review) (aka the Cumberlege report), as well as the all of the above by the families affected - who have worked like hell to ensure greater awareness of sodium valproate side effects, and to pressure the implementation of change.
Epilepsy Sparks Insights, my written articles, blog, and videos - allow me to help inform the world of some exciting work going on in the spheres of epilepsy, and provide a voice for the 65+ million people with epilepsy.
Now if you've found this podcast interesting, cool, or eyeopening; please check out my Patreon page at www.patreon.com/torierobinson and consider becoming a member - where you can gain sole access to weekly posts, early access to blogs, videos, and more.
Take care everyone. Education is power.
Oh, and have a happy new year!
For more information, see:
The Epilepsy & Pregnancy Register: epilepsyandpregnancy.co.uk
European Medicines Agency: https://www.ema.europa.eu/en/medicines/human/referrals/valproate-related-substances-0
UK Gov: https://www.gov.uk/guidance/valproate-use-by-women-and-girls#history
Note:
TR: Torie Robinson
JM: Jim Morrow
*Replaced by Commission on Human Medicines in 2005
**Sodium valproate has been on the market since 1973 (in the UK)
