The effect of antiepileptic drugs on thyroid function in children

The effect of antiepileptic drugs on thyroid function in children

Interactions between everything to do with thyroid (hormones, tests, etc.) and medicines has often been discussed here. I remember some specific mentions of the impact of anti-epileptics. This is just another abstract which identifies that there are potentially very significant interactions between anti-epileptics and thyroid.

Seizure. 2013 Sep 16. pii: S1059-1311(13)00253-7. doi: 10.1016/j.seizure.2013.09.006. [Epub ahead of print]

The effect of antiepileptic drugs on thyroid function in children.

Yılmaz U, Yılmaz TS, Akıncı G, Korkmaz HA, Tekgül H.


Department of Pediatric Neurology, Dr. Behçet Uz Children's Hospital, Izmir, Turkey. Electronic address:



Limited and conflicting data exist for the influence of antiepileptic drugs on thyroid function in children.


The aim of this study was to investigate the effects of phenobarbital, valproate, carbamazepine, oxcarbazepine, and levetiracetam monotherapy on thyroid function in daily clinical practice during a 12-month treatment period.


A total of 223 children (103 females and 120 males) with new onset and controlled epilepsy treated with valproate (n=129), phenobarbital (n=33), carbamazepine (n=36), oxcarbazepine (n=14), levetiracetam (n=11) were enrolled in the study. Serum free thyroxine (fT4) and thyroid-stimulating hormone (TSH) levels were measured before and at first, sixth and twelfth months of therapy.


At baseline, average fT4 and TSH concentrations were not different between the drug groups. Valproate-treated patients had decreased fT4 and increased TSH levels at months 1, 6, and 12. Carbamazepine-treated patients had decreased fT4 levels at months 1, 6, and 12 and increased TSH levels at months 1, and 6. Phenobarbital-treated patients had decreased fT4 levels at months 1, and 6, and increased TSH levels at months 6 and 12. Oxcarbazepine-treated patients had decreased fT4 levels at month 1. Levetiracetam-treated patients showed no significant change of fT4 and TSH at any times. The frequency of subclinical hypothyroidism at month 12 was 28% in valproate, 21.4% in oxcarbazepine, 18.2% in phenobarbital, 13.9% in carbamazepine, and 0% in levetiracetam groups.


Our data suggest that all antiepileptic drugs studied except levetiracetam had varying degrees of deleterious effects on thyroid function.

Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.


AED, Antiepileptic drugs, Children, Subclinical hypothyroidism, TSH, Thyroid function, antiepileptic drug, fT4, free thyroxine, thyroid stimulating hormone



[PubMed - as supplied by publisher]


Image: The anticonvulsant drugs sodium valproate, stiripentol, clobazam and midazolam. 29 October 2009 Author Colin

17 Replies

  • If I had an epileptic child I know which drug I would prefer. But which would the NHS prescribe as a first choice?

    That would be a very worrying report if I were epileptic or the parent of an epileptic child. You wonder how many parents have expressed concern over their child's wellbeing only to be told it is a side effect or it is caused by the epilepsy?

  • I don't know about children, but the first choice for adults was always carbamazapine because it was cheapest. My doctor was even happy to get me up to the highest possible dose before changing to something else when carbamazepine was clearly not working! Then, instead of changing my medication, I was prescribe phenytoin IN ADDITION to the high dose of carbamazepine. (Blood tests showed I was almost toxic but I felt most definitely toxic. It was horrible! It wasn't until I was referred to a psychiatrist in London (because the cheapest psychiatric drugs they could prescribe also weren't working) that I was switched to Epilim. He felt there was a connection between the epilepsy and psychiatric symptoms, which there were, and I did start making improvements on both counts. He also changed my psychiatric medication.

    Of course, full improvements weren't made until a year later when a very psychiatrist prescribed t3. Miraculous recovery. I don't think it's a surprise that I was diagnosed hypothyroid a couple of years later...

    The sad thing is, often the parent doesn't get a say in which drug is prescribed even when they do know the associated risks and ask :(

  • I knew you'd be along, Carolyn. As you say. Quite.


  • Yes, the mistreatment of my various conditions is a bit of a sore point. I have a lot of wasted years to make up for and I'm making sure I do it :D

    This is the trouble when you have the beginnings of hypothyroidism presenting as a psychiatric condition - you get treated like a hypochondriac and no-one listens when you tell them you are feeling worse on the medication you have been given.

    Carolyn x

  • I was treated like a hypochondriac and I don't even have a thyroid. To quote Paul Robinson, a case of missing the elephant in the room!

  • This is really interesting, ok I'm not a child but I am on both levothyroxine and carbamazepine and I knew they both didn't agree with each other. My bloods have just been checked and I'm waiting for the results but I feel that after 6 months of taking carbamazepine my thyroid levels have dropped. I have been on almost the same dosage of levo for 18yrs although I'm being told it won't be my thyroid levels that's causing my problems.

  • Do you have thyroid blood test results? If you don't, ask for them. Post them in a new question and someone will be able to advise you whether it is your thyroid or not. It probably is. Blood tests aren't always helpful in determining whether someone is on the right dose or even the right thyroid medication. Sometimes, as long as your results are in the normal range, the doctor says 'normal' but this level isn't necessarily right for you. You may find you feel a lot better on a higher dose of thyroxine.

    I felt horrid on carbamazepine but better on Epilim. It might be worth asking your doctor whether it is possible to change. Of course there are risks associated with switching epilepsy drugs in that you could start having seizures again so make sure you are referred back to a neurologist for this.

    I hope you find the answer so you can feel well again soon.

    Carolyn x

  • Another quick note: carbamazapine can affect absorption and increase metabolism of levothyroxine so you will likely need a higher dose than other people. People with a healthy thyroid will naturally compensate for this but if you are hypothyroid you need to compensate with a higher dose. Also TSH may not respond to these changes in the way you would expect.

  • Thanks. My problem is that I had a 2nd tt in May and my bloods were tested in June so the gp was reluctant to repeat so quickly but i forced them to take them , after being diagnosed with graves 19 yrs ago I know myself without the bloods that I have dropped. I felt like crap since being put on carbamazepine but I am waiting for an update from my neurologist as I have just had another scan to make a decision on whether I've to have surgery, I should say that I take carb for tn not epilepsy that may be caused by my aneurysm which is awkwardly placed. I am currently fighting fire with fire on where all my meds should be x

  • Oh gosh! What a complicated situation to be in! I hope they manage to sort it out successfully.

    Carolyn x

  • Thanks hopefully I'll get it all sorted sooner rather then later and get back to some sort of normality x

  • I was rather expecting some comments like yours. Just because this study is in children obviously doesn't mean it has no applicability to adults - though the effect may be greater of smaller or somewhat different in various ways.

    Hope the paper helps you to resolve your problems.


  • not sure if anyone else is aware of this, but, for women with epilepsy, especially catamenial (sp?) epilepsy (connected to the cycle/hormones), have a look at the help that natural progesterone (bio-identical) cream can give - as (and real research is behind on this, but agreeing with the experience of some - came across some being done in Australia - but there could be more), it can help balance out the female hormones - as some may know if you tend to be 'osetrogen dominant' that can 'interfere with the mission of T4 in thyroxine converting to T3' (as I think Dr. John Lee phrased it), and, other research shows that oestrogen is pro-seizure (can't think of the proper terminology, sorry), and progesterone is 'anti-seizure.'

    (Must be natural proesterone, though, not the synthetic progestin.)

    My daughter developed epilepsy at 13 at puberty (must have been the rush of hormones from the endocrine system messing things up), and seizures occured during her cycle when progesterone had it's low stages.

    Thyroid disease runs in our family in the females (my 83 year old mom is the latest to be finally diagnosed after being admitted to hospital with AF heart probs) ..

    My daughter has symptoms of thyroid disease (can't determine if hyper or hypo at the moment), especially after giving birth 2 years ago.

    Childbirth in 1990 was the final trigger for my Hashis.

    A good site for natural progesterone in the U.K. is Wellsprings (if it's not ok to add that bit please remove, Admin, but I spent a lot of time writing the rest - I'll edit if possible if you would like me to).

  • When you mention "thyroid disease runs in our family", "AF heart probs" and "can't determine if hyper or hypo" it sounds a bit like Thyroid Hormone Resistance. My mum had hypo symptoms and AF heart problems. My sisters all have fatigue and need to sleep a lot. My son had more extreme symptoms, including a large goitre and pain/fatigue akin to fibromyalgia. His Free T3 however was in the high normal range. I also have 2 female cousins who have developed similar problems.

    My son is now responding very well to a high daily dose of T3 (as recommended by Dr John Lowe in his book). My son has a very sympathetic NHS endocrinologist, who although unable to prescribe T3, does monitor his condition. He has also referred my son to a specialist team in Addenbrookes Hospital in Cambridge who are investigating rare thyroid conditions..

  • A friend of mine has been on carbamazapine for years - lots of weight gain. But, if it is stopped, the result is incredibly severe suicidal depression. You win some, you lose some.

  • I am glad that you posted that - clearly clinical decisions should NOT be made on the basis of a single research paper.

    Hoping that it might simply raise awareness, even 'click' in someone's mind as to what could be going on and, by so doing, initiate a discussion with doctors.


  • Carbamazepine is often used as a mood stabilizer, as are some of the other anticonvulsant drugs. That could explain your friend's unfortunate reaction :(

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