Anti-epileptic drugs

Anti-epileptic drugs

Questions from healthcare professionals

Q: Are you aware of any problems with the supply of tegretol liquid? I have heard that it is "long term unavailable".

A: We have contacted Novartis who confirm that they have stocks of tegretol liquid. If any pharmacy is experiencing problems in supply, they should contact Novartis who will supply them directly (rather than via a wholesaler).
November 2011

Q: Do you have any good reference material in relation to antiepileptic drugs and antibiotic drug interactions?

A: One source of information is Stockley's 'Drug Interactions' (often considered the gold standard). There is also a chapter in 'AntiEpileptic Drug Interactions A Clinical Guide' by Philip Patsalos.
October 2011

Q: Is there an increased risk of tonic clonic seizures for someone taking citalopram at increasing dosages?

A: There is a slight increase in risk but, if someone has epilepsy and is on anti-epileptic drugs, the risk of worsening the epilepsy is low. The reaction to any medication is obviously individual and any comment on risk is generalised.
September 2011

Q: Is there available a specific assessment tool that can be used in monitoring the side effects of anticonvulsant medication?

A: We are not aware of a specific assessment tool. However, it is important to be aware of the dose–related, chronic, idiosyncratic and teratogenic side-effects of anti-epileptic drugs. These are listed in the Summary of Product Characteristics, on the medicines guide website (at www.medicines.org.uk/guides/epilepsy) and on the Epilepsy Society website at http://www.epilepsysociety.org.uk/AboutEpilepsy/Treatment/Antiepilepticdrugsusedinadults
July 2011

Q: Is there any call to increase a person's AED's because they have put on weight even though they are seizure free (because of the risk of losing a driving licence and subsequently job & livelihood)?

A: In standard practice, AED dose increases are managed in terms of level of seizure control and are not usually dependent on weight (over the age of around 13 years). So changing dosage because of weight gain in adults is not standard. However, all approaches to managing seizures with medication needs to be tailored to the individual.
Answered by Epilepsy Society's medical team
June 2011

Q: Is it best to take Epilim Chrono once or twice day (that is, splitting the dose & taking twice a day)?

A: According to the patient information leaflet (http://www.medicines.org.uk/emc/medicine/10912/PIL/Epilim+Chrono/) Epilim chrono can be taken either once or twice a day. This will largely depend on the individual taking the medication, and their lifestyle. For example, some doctors will suggest taking it twice a day so that if one dose is forgotten it is less of a problem than missing an entire day's dose.
May 2011

Q: I work in addictions and at the present time we are detoxing individuals from drugs (primarily methadone, heroin and cocaine). Many individuals also use benzodiazepines (either prescribed or otherwise).  Individuals are detoxed using neuroelectrolysis therapy (medication free). Some individuals have had seizures during detox. Is there a way of identifying cause of seizures and knowing whether they could be due to the detox?

A: We are not familiar with neuroelectrolysis therapy and therefore do not know of any evidence of its efficacy in managing detoxification nor whether it may cause seizures. However, it is known that withdrawal of benzodiazepines may result in drug withdrawal seizures, and this would usually be managed with very gradual tapering and use of gradually reducing doses.
May 2011

Q: Is there any guidance on starting anti-depressants for a patient with depression who has epilepsy and takes anti-epileptic drugs? Seizure-recurrence is of prime concern.

A: Any initiation of drug treatment in patients with co-morbidities, or who is taking other medication, needs to be considered and tailored for each individual. However, the following paper may be of interest to you:
The pharmacological treatment of depression in adults with epilepsy. Mula M, Schmitz B, Sander JW. Expert Opin Pharmacother. 2008 Dec;9(18):3159-68.
January 2011

Q: I have a patient who refuses to take Epanutin capsules, or syrup because of the bitter taste. He is on a dose of 300mg. What are the alternatives?

A: There is no simple solution to this. An alternative may be to use 100mg phenytoin tablets which are plain white and not too large, although this would require three tablets per dose. One consideration is whether the individual has had recent blood level monitoring. It could be that if the blood levels are high and therefore could be making him feel unwell, this could be a reason for him refusing the medication. In this situation and medication review may be useful.
Answered by Epilepsy Society's pharmacy team.
January 2011

Q: How would you manage a lamotrigine rash in an older adult with Down's Syndrome and Alzheimer's disease associated with seizures?  Is it sufficient for the rash to be treated by steroids by the GP or should the drug be withdrawn and replaced?

A: If the rash is an allergic response to lamotrigine, it is important that lamotrigine is stopped and replaced with a suitable alternative anti-epileptic drug. However, any withdrawal from anti-epileptic drugs should be carefully managed with the input from an epilepsy specialist.
January 2011

Q: Can anti-epileptic drugs cause developmental delay in children with epilepsy?

A: Children with epilepsy can experience developmental delay because of the type of epilepsy they have: for example some childhood epilepsy syndromes are associated with developmental delay. The impact of anti-epileptic drugs varies from one drug to another, and from one individual to another. You can find a list of side effects of anti-epileptic drugs on the medicine guides website (opens a new window). However, it is important to note that a holistic view of an individual with epilepsy can be helpful in determining the cause of developmental issues, which may or may not be related to medical treatment. You can find out more about this issue in the paper on 'Drug treatment of paediatric epilepsy' within our library of articles on this website.
November 2010

Q: I have a patient who is 12 months old and has been diagnosed with tonic clonic seizures. She has been taking carbamazepine for the last two months but is still having seizures (about 1 every 10 days). There are no specific triggers. Can it be the case that a person takes anti-epileptic drugs yet continues to have seizures?

A: The aim of anti-epileptic drugs is to stop seizures from happening. Different anti-epileptic drugs work for different seizure types, so the type of seizures is important when starting treatment. Find out more about this on our website. If treatment has started but is not controlling the seizures, this could be for several reasons. For example, the drug chosen does not work for the type of seizure the individual has or the dose of drug is not sufficient for the individual. There are also individual patient factors that could mean that a drug is not suitable for that individual. In cases such as these, another anti-epileptic drug may be found to be more suitable, and there may be a degree of 'trial and error' to get the right drug at the right dose for any given individual. You can find out more about treatment with anti-epileptic drugs within the 'medical treatment of epilepsy' section of the library of articles on our website. 
November 2010

Q: What are the possible effects of withdrawing from anti-epileptic drugs, apart from seizure recurrence? Would the body crave the drugs?

A: We are not aware of any evidence that the body craves for anti-epileptic drugs during withdrawal, and most anti-epileptic drugs do not have withdrawal effects. Any change in the person's behaviour during withdrawal should be considered alongside the history of their seizures, as seizure recurrence can happen during withdrawal. In general, slow withdrawal from anti-epileptic drugs is preferable, to reduce the likelihood of seizure recurrence and withdrawal effects.
Answered by Epilepsy Society's medical team.
September 2010

Q: Are there any contra-indications between anti-epileptic drugs (AEDs) and medications available for excess salivation?

A: Some people take hyoscine hydrobromide in either tablet form (such as 'Kwells') or as patches (such as 'Scopoderm'). This works for some individuals although it may not work for everyone. It is also worth checking the contra-indications for each anti-epileptic drug (AED) that the individual is taking. Information on each AED can be found on the medicines guide website (opens a new window)
Answered by Epilepsy Society's pharmacy team.
August 2010

Q: What are the emc medicines guidelines?

A: eMC is the electronic Medicines Compendium, containing information about UK licensed medicines. This website contains the patient information leaflets for many medicines, including anti-epileptic drugs. Find out more directly from the website (opens a new window) 
April 2010

Q: Are there any new AEDs on the horizon?

A: Please see the article 'New Anti-epileptic Drugs' in the medical treatment of epilepsy section of this website.
April 2010

Q: Are you aware of any differences in bioavailability between different sites of manufacture of AEDs?

A: We have heard anecdotal reports of differences in bioavailability between the same drug manufactured at different sites (parallel imports). However, we are not aware of any 'proof' of this situation.
Answered by Epilepsy Society's pharmacy team.
February 2010

Q: How should the time zone difference be managed in terms of medication for epilepsy? For example, a patient going on a three-week holiday to Japan, which is around 10 hours ahead of GMT.

A: Whether to manage a change in time zone by adjusting the timing of taking medication depends on several factors, including the length of stay abroad and the time zone difference. For example for people who are going to areas with a 10 – 12 hour time difference and who take their medication twice a day, 12 hours apart, they may wish to continue to take their tablets as normal.
February 2010

Q: Are there any contraindications between anti-epileptic drugs and glucosamine or chondroitin?

A: As glucosamine and chondroitin are classified as food supplements, there is very little information available on drug interactions, and we are not aware of any relevant scientific study. However, common side effects of glucosamine and chondroitin include nausea, vomiting, diarrhoea and constipation, all of which could have an impact on the absorption of anti-epileptic drugs.
January 2010

Q: What research has been done specifically on the difference in therapeutic effect between brand and generic forms of lamotrigine?

A: You may find the following paper helpful: Clinical consequences of generic substitution of lamotrigine for patients with epilepsy (opens a new window) LeLorier J, Duh MS, Paradis PE, Lefebvre P, Weiner J, Manjunath R, Sheehy O. Neurology. 2008 May 27;70(22 Pt 2):2179-86
November 2009

Q: Are there any standard guidelines for recommending patients on long term AEDs to take vitamin D and calcium?

A: This is a subject that is still very much open to discussion although, in practice, some professionals encourage people to take vitamin D and calcium. This subject is mentioned in the paper 'Epilepsy and Women' (pdf), along with some references at the end of the paper.
September 2009

Q: How important is it that anti-epileptic drugs are taken at the same time each day? Can variations of up to 3 hours make a different to effective treatment and seizure control?

A: The importance of timing and intervals for taking anti-epileptic drugs depends on the pharmacological properties of the drug, and the individual taking it.

A useful reference for information is the following: ‘Anti-epileptic drugs — best practice guidelines for therapeutic drug monitoring: A position paper by the Subcommission on Therapeutic Drug Monitoring, ILAE Commission on Therapeutic Strategies’ (2008) by Patsalos PN, Berry DJ, Bourgeois BFD, Cloyd JC, Glauser TA, Johannessen SI, Leppik LE, Tomson T and Perucca E in the journal Epilepsia 49 (7): 1239–1276.
August 2009

Q: In a patient with alcoholism, what strategies can be put in place to encourage medication concordance? In those who do not intend to stop drinking, what are the implications of stopping treatment compared to treatment taken on a ‘when remembered’ basis?

A: One of the cornerstones of concordance is information and understanding about the needs, risks and benefits of treatment. This encourages individuals to understand why anti-epileptic treatment works best when taken regularly, and the risks of abruptly stopping treatment. There may also be other issues around why an individual is not taking treatment, other than remembering to take it. A frank discussion of this can be helpful to identify what support or strategies would be helpful depending on the reason behind poor compliance. For individuals who find it difficult to remember to take their medication, there are various medication aids available. See useful addresses – suppliers of equipment on this website. If an individual does not intend to stop treatment, it may be worth considering not insisting on treatment. This would need to be decided in the context of each individual, their epilepsy, and the risks to their health due to their epilepsy. 
September 2008

Q: Is there a known connection between long-term use of Levetiracetam and reduced bone mineral density or quality?

A: We are not aware of any known connection at this time. There is more information about this drug, and all other anti-epileptic drugs, on the website of the British National Formulary or the Medguides website.  
May 2008

Q: Is there any evidence that the Flu vaccination can raise the levels of anti-epileptic drugs, and if so, which ones?

A: We are not aware of any evidence that the Flu vaccination can raise the levels of any anti-epileptic drug. 
May 2008

Q: When phenytoin is given intravenously by infusion, is it important to use a filter?

A: For information about giving phenytoin, please refer to the instructions in the BNF (British National Formulary) for details. Please note: NSE is unable to provide a medical opinion on specific cases. Responses contain information relating to the general principles of investigation and management. Answers are not, and should not be assumed to be, direct medical advice.
April 2008

Q: Is stiripentol available on an NHS prescription even though it is not licensed in the UK?

A:  Theoretically it can be prescribed on the NHS if the GP is willing to do so. However, if the local PCT are not able or willing to fund treatment with it, the GP may not be able to prescribe it. 
April 2008

Q: I have a patient, taking sodium valproate and carbamazepine, who is very tired and sleeps in the day time. Can anti-epileptic drugs cause excessive fatigue in individuals?

A: Anti-epileptic drugs can cause fatigue, and this can be more likely in individuals with a brain injury. High drug and ammonia levels are more likely to cause fatigue, although it can still occur even if the levels are not high. A review of the individual's medication may be beneficial in this example.
January 2008

Q: Are there any current guidelines or protocols on withdrawing treatment with phenytoin?

A: If phenytoin is being withdrawn in an individual who is seizure free, 50mg a month would be unusual. However, there is little evidence to support this. If phenytoin is being withdrawn in an individual with active epilepsy, a useful reference is: Duncan, JS, Shorvon, SD, Trimble, MR. Discontinuation of phenytoin, carbamazepine and valproate in patients with active epilepsy. Epilepsia 1990; 31: 324-333
January 2008

Q: Can Levetiracetam be used for Juvenile Myoclonic Epilepsy (JME)?

A: Levetiracetam is indicated in the treatment of JME. For more information on its use for JME, see MedGuides or the British National Formulary website.
December 2007

Q: Has Topiramate any activity in treatment of typical abscence seizures?

A: Topiramate can be used for this but not as a first line treatment.
November 2007

Q: Is there evidence that topiramate taken with oxcarbazepine can cause undue tiredness after a night's 9 hour sleep?

A: Both these anti-epileptic drugs can cause drowsiness. For more information about medication for epilepsy, side effects and interactions, go to MedGuides or the British National Formulary website.
October 2007

Q: Can a patient taking the anti-epileptic drug Epilim (sodium valproate) also take the food supplement Glucosamine Sulphate?

A: We are not aware of any contraindications between Epilim and Glucosamin Sulphate. For more information on anti-epileptic drugs and their contraindications see the British National Formulary website or the MedGuides.
September 2007

Q: Is there a specific dose conversion from oral sodium valproate E/C to rectal carbamazepine?

A: No, these are very different drugs.
July 2007

Q: Have you ever come across any foods or drinks which would interfere with Epilim or Tegretol Retard?

A: In general, there are no particular foods or drinks that should be avoided by people with epilepsy. If there is a known interaction between a particular anti-epileptic drug and a food/drink, this will be indicated on the patient information leaflet, which can be read on Medicines.org.uk.
July 2007

Q: Can delirium due to carbamazepine overdose cause slow background activity on EEG in an epileptic adolescent?

A: Overdose with carbamazepine could slow the EEG.
July 2006

Q: Can you tell me if there are any drugs to take which will enable the person with epilepsy to have an aura so they have an idea of when a seizure/absence is about to happen?

A: There are no such drugs, and it wouldn't be recommended in any case, as an aura is itself a seizure (simple partial seizure).
June 2006

Q: I’ve heard that a new form of slow release sodium valproate capsule that can be sprinkled on food is likely to become available. Do you know which company is responsible for this and is it likely to be available soon?

A: Sanofi, the company that manufactures Epilim, has developed ‘chronospheres’ which can be sprinkled directly onto food. These are not yet available but they hope to launch them sometime next year - no likely date available. They are being launched in France initially. In the meantime it is possible to crush up the Epilim crushable tablets and the resulting powder may be added to food.
December 2005

Q: Has any research been carried out into whether epilepsy is better controlled using proprietary drugs opposed to generic drugs?

A: No research has been carried out in this area.
October 2005

Q: Where would I find evidence to support the importance of brand continuity in epilepsy medication?

A: The following resources may be of use: Consistency of supply of antiepileptic drugs. Ed. GA Baker. RSM Press 2005. ISBN 1-85315-676-0 Branded versus generic drugs (article from NSE’s members' magazine Epilepsy Review).
October 2005

Q: Can long-term use of valproate cause mood swings in women?

A: This is unlikely as valproate is a mood stabilizer.
August 2005

Q: In a person with partial epilepsy who has a partial response to carbamazepine, is there any benefit from switching to oxcarbazepine?

A: The main reason for switching would relate to tolerance as oxcarbazepine is usually tolerated better than carbamazepine. If the dose can then be increased there might be efficacy benefits.
July 2005

Q: Has anybody come across a link of increased seizure risk in patients taking anti-epileptics and oxycontin/oxynorm medication? Or is there any type of suspected interaction between these drugs?

A: We are not aware of any interaction or risk of increased seizures.
June 2005

Q: Is there a recognized withdrawal syndrome associated with long-term phenytoin use, as the dose of the drug is reduced? If so, what are the symptoms?

A: If phenytoin is withdrawn too quickly then withdrawal seizures may occur. Withdrawal should be done slowly to prevent such problems.
May 2005

Q: What advice can be given for patients recently prescribed valproate who are suffering hair loss? Will the loss continue while taking the drug? Is it reasonable to switch AED?

A: Valproate-associated hair loss is usually only temporary. The hair often grows back darker and more wavy. The decision as to whether to change AED is best made jointly by the doctor and the patient, and will depend partly on how significant the side effect is to the patient. See the chapter Medical treatment of epilepsy in our articles section.
May 2005

Q: What is the difference in kinetics between valproic acid and sodium valproate? Does this make either of them more effective than the other?

A: There is no difference in efficacy between valproic acid and sodium valproate, and no major kinetic differences.
April 2005

Q: What is the difference between phenytoin and methylphenytoin regarding kinetics and efficacy?

A: Methylphenytoin is not used anymore.
April 2005

Q: There appears to be controversy around using buccal midazolam in the community. I have heard that children are being admitted to hospital and given a test dose prior to prescription of buccal midazolam. Is this ethical and correct? Also I have heard rumours that it is a date rape drug - is this correct?? Is there a nationally agreed policy on one or two doses of midazolam as manufacturers Safe Products leaflets suggest two doses. They are also marketing a midazolam dose for prolonged complex partial seizures - is there any evidence to support this?

A: The issue about admitting for a test dose is unproven - it is really up to the prescribing physician. Essentially it is a false situation as the children are not having seizures at the time. Midazolam is one of the date rape drugs. There is no nationally agreed policy other than that an individual protocol needs to be drawn up (NICE). There is no evidence that treatment of prolonged complex partial seizures should be any different to generalised tonic clonic seizures.
February 2005

Q: Are there any alternative formulations – for example suppositories - of sodium valproate, tegretol and levetiracetam, for patients with learning disabilities who have difficulty with oral medication, and where injections are not an option?

A: Sodium valproate is available as suppositories on a named patient basis, imported by IDIS World Medicines. The bioavailability is similar to the oral preparation, although absorption is slower. Carbamazepine suppositories are marketed in the UK as Tegretol produced by Cephalon UK Ltd. They are available as 125mg and 250mg. 125mg given rectally is approximately equivalent to 100mg given as a tablet, but dose may need to be adjusted according to clinical response. Recommended maximum dose of one gram daily in four divided doses. The suppositories are licensed for short-term use when oral therapy cannot be taken. Levetiracetam is not available in a rectal formulation. An oral liquid preparation has recently been launched in the UK, which may be of some use for patients unable to swallow tablets.
January 2005

Q: Is topiramate safe in porphyria cutanea tarda?

A: Topiramate can trigger acute porphyria in an in vivo model of porphyria. Because of this (the model is highly predictive for humans) it is contraindicated in patients with porphyria. Gabapentin and probably pregabalin are safer choices.

December 2004

Q: It is common practice in care homes to administer medicines crushed and mixed with food. Some anti-epileptic drugs (e.g. epilim) should not be crushed or chewed. Which medications are these, and what are the consequences to crushing the drugs and how would one deal with clients who can only take medication in this way?

A: It is never advisable to crush anti-epileptic medication unless this is a specified way of taking it. All anti-epileptic drugs come in different formulations, for example liquid, crushable tablets, enteric coated tablets, sprinkle capsules. The formulation for any particular person should be chosen according to how they are able to take medication. This is important to encourage compliance. However the formulation of anti-epileptic drugs – particularly phenytoin and carbamazepine – should not be switched without specialist input. If the formulation prescribed is not suitable for a particular person, the prescribing doctor should be consulted.
September 2004

Q: Can phenobarbitone cause nystagmus?

A: Adverse neurological effects, including nystagmus, may be seen when there are toxic levels of phenobarbitone in the blood.
September 2004

Q: Do anti-epileptic drugs decrease libido in males in the long term?

A: Some older drugs - primidone and phenobarbitone - have been associated with this problem, but not other anti-epileptic drugs as far as we are aware.
September 2004

Q: When is the best time to take blood for drug levels, does it have to be a certain number of hours after or before medication is taken? How would it affect the results?

A: The ideal time to take blood for drug levels is just before medication is taken. However this is often not practical. Instead, blood can be taken at any time, but it is important to make a note of the exact time of the last dose of medication, and the exact time that the blood sample is taken. This information can then be used to determine the blood level of the drug.
August 2004

Q: How is cognitive functioning affected by the long-term use of pheyntoin?

A: The use of phenytoin particularly in high doses may affect the cognitive functioning of some people. This may compounded by background aetiology and concomitant AEDs.
August 2004

Q: Is midazolam licensed for intranasal use yet and if so is there a specific product available?

A: Midazolam is not currently licensed for the treatment of status epilepticus.
July 2004

Q: What are the effective plasma and brain levels of anti-epileptic drugs? Is there a reference where I can find such information?

A: A reference for the new AEDs is: Johannessen SI et al. Ther Drug Monit 2003; 25:347-363. There are also many references quoted in this publication regarding the older AEDs.
June 2004

Q: Dupuytren's contractures may be a rare chronic side effect of phenobarbitone treatment particularly in high doses. It needs to be treated surgically if it causes limb dysfucntion.

A: How common is Dupuytren's contracture and frozen shoulder in women taking a small dose of phenobarbitone in the long term? What can be done to treat these symptoms?
June 2004

Q: Do you have any information about which treatment for hayfever interferes least with anti-epileptic medication?

A: Cetirizine has been used for many people at Epilepsy Society's residential centre, who are also taking anti-epileptic medication, without any adverse effects to date. It doesn’t interact with anti-epileptic medication, as far as we are aware.
June 2004

Q: I am looking for evidence to support (or not) the routine monitoring of liver and kidney function with annual blood tests for patients established on AEDs.

A: The following paper is on this subject: Harden CL. Therapeutic safety monitoring: what to look for and when to look for it. Epilepsia 2000; 41 (Suppl. 8): S37-44.
May 2004

Q: Are the new anti-epileptic drugs better than the old ones? If so, how?

A: NICE has just issued guidance on the use of newer anti-epileptic drugs. The full guidance discusses the advantages and disadvantages of the newer and older anti-epileptic drugs. This can be found on the NICE website
May 2004

 Q: Can nocturnal epilepsy be treated with anti-epileptic drugs given just before sleep with no other doses in the morning?

A: Anti-epileptic drugs (AEDs) do not act in the short-term to prevent seizures from occurring. When AEDs are taken, the level of the drug in the bloodstream builds up over time and is kept at steady state by regular intake of the AED, causing the person’s seizure threshold to increase. A higher seizure threshold makes seizures less likely to occur. As for all types of epilepsy, nocturnal epilepsy is treated with AEDs taken at regular intervals, usually two or three times a day depending on the drug.
January 2004

 Q: In stroke patients, if I prescribe AEDs prophylactically, for how long would this ideally be?

A: There is no place for prophylactic AED treatment in stroke. 
January 2004

Please note: Epilepsy Society is unable to provide a medical opinion on specific cases. Responses contain information relating to the general principles of investigation and management. Answers are not, and should not be assumed to be, direct medical advice.