Different Types of Anti-Epileptic Drugs (AEDs) and Their Side Effects

Published: 08 Dec 2022

Anti-epileptic drugs (AEDs), also known as anticonvulsants or anti-seizure medications (ASMs), are the most commonly used treatment for epilepsy in the UK. The main use of AEDs is to reduce the severity and frequency of seizures in people with epilepsy.

There are multiple different formulations of AEDs, and each drug comes with a list of potential benefits and risks which vary in rarity and severity. This article looks at the therapeutic effects and side-effects of some of the most common AEDs.

General side effects of AEDs

AEDs may have different formulations, but some AED side effects are common between drugs. Drowsiness, a lack of energy, tremor, and skin rashes are all commonly listed adverse effects, along with a dry mouth and gastrointestinal effects. Neurological effects are common, such as dizziness and memory issues, as are behavioural side effects including agitation, aggression, behavioural disorders, and generally abnormal behaviours.

All antiepileptic drugs may be associated with a small increased risk of suicidal thoughts and behaviour according to a review conducted in 2008 by the European Medicines Evaluation Agency or EMEA (now the European Medicines Agency/EMA). This prompted the MHRA in the UK and the Food and Drug Administration (FDA) in the US to issue safety warnings.

At the time, the EMEA advised that the benefits of anti-epileptic medicines outweighed the concurrent small risk of suicide and suicidal ideation. Further research has been completed since 2008 which indicates that the suicide risk from anti-epileptic drugs increases significantly in people with certain comorbidities including depression, but risk levels do not increase outside of these groups. However, the BNF epilepsy page still carries a general caution based on the original EMEA notice from 2008, as does the MHRA bulletin.

Per the epilepsy guidelines published by NICE and the previously mentioned prescribing recommendations in the BNF, anti-seizure medications should be prescribed one at a time (known as monotherapy) where possible, as combining two or more medications increases the risk of adverse effects and drug interactions. Moreover, ‘spontaneous adverse reactions’ have been reported even when switching between a name-brand anti-epileptic drug and its generic counterpart. This means that the process of switching between medications must be undertaken cautiously and closely monitored by a medical professional.

Common types of AED and their side effects

There are many AED seizure medications available in the UK. Certain medications are more effective at treating seizures associated with particular types of epilepsy and epileptic syndrome, whereas others display efficacy in reducing multiple different types of seizure. 

The NHS epilepsy webpage lists five common types of AED used in the UK as first-line treatments for seizures:

Sodium valproate (UK brand names: Dyzantil®; Epilim®; Episenta®; Epival®)

Sodium valproate (a sodium salt of valproic acid, or VPA) is commonly prescribed for the treatment of all forms of epilepsy in children and adults. It has been found to be more effective than other drugs as a medication for generalised tonic-clonic seizures and is the current first-line treatment for these.

According to the British National Formulary (BNF), valproate has systemic effects on the liver and metabolism. This means that monitoring of liver function is required before starting valproate and for six months after starting AED treatment.

Hepatic (liver-related) disorders are listed as common/very common side-effects of the drug alongside gastrointestinal effects like vomiting and diarrhoea. The BNF recommends that valproate be withdrawn if persistent symptoms of vomiting/abdominal pain, anorexia, jaundice, oedema, malaise, drowsiness, or loss of seizure control are present—this could indicate hepatic dysfunction (liver failure) or pancreatitis. The BNF therefore recommends that patients and their carers should be advised on how to spot early signs of liver failure or pancreatitis. Prescribers are advised to avoid using valproate in people with pre-existing liver impairment or metabolic disorders.

Some blood disorders are listed as common side-effects, including thrombocytopenia (deficiency of platelets in the blood) and hyponatraemia (low sodium levels in the blood). It is therefore recommended that a full blood count be completed before a patient is started on sodium valproate.

Sodium valproate has been found to be teratogenic, meaning it can cause structural changes in a foetus or child in utero if the drug is administered during pregnancy. Of children born to mothers who took sodium valproate during pregnancy, 1 in 10 are at risk of being born with a birth defect, with 4 in 10 at risk of being born with a developmental or learning disorder.

As a result, the BNF states that sodium valproate must not be used in women, girls, or anyone of childbearing potential (defined as someone who has begun menstruation, is premenopausal or is otherwise capable of bearing children). Use of sodium valproate in people of childbearing potential is only allowed if:

a) The patient has followed the Valproate Pregnancy Prevention Programme as set out by the Medicines and Healthcare products Regulatory Agency (MHRA), or;

b) All other seizure treatments are assessed to be ineffective or poorly tolerated in a patient in the judgement of an experienced specialist medical professional.

Common/very common side effects of sodium valproate include, but are not limited to: Abdominal pain; alopecia; anaemia (deficiency of red blood cells); confusion; deafness; diarrhoea; drowsiness; haemorrhage; hallucination; hepatic (liver) disorders; hypersensitivity; hyponatraemia (low blood sodium levels); memory loss; irregular menstruation; nausea; nystagmus (involuntary movement of the eyes); increased seizures; thrombocytopenia (blood platelet deficiency); tremor; urinary disorders; and vomiting.

Carbamazepine (Curatil®; Tegretol®)

Carbamazepine is currently indicated as a second-line or first-line adjunctive (or ‘add-on’) monotherapy for focal seizures. National Institute of Health and Care Excellence (NICE) guidance states that carbamazepine may exacerbate seizure symptoms in people with absence seizures and atonic or tonic seizures, or in patients with Dravet or Lennox-Gastaut syndromes. In people with myoclonic seizures, NICE expressly recommends against the use of carbamazepine for the same reason.

Following a 2021 safety review, carbamazepine use during pregnancy was found to be associated with an increased, dose-dependent risk of the development of congenital malformations in foetuses and children. As with many AEDs, caution is currently advised to those who are pregnant, or who may become pregnant during treatment for epilepsy, when considering whether to start carbamazepine.

Although there is less information available than on sodium valproate about the risk of hepatic, renal and blood disorders, the manufacturers still advise that liver function, kidney function and blood counts be performed, although the BNF questions the evidence for testing in their carbamazepine monograph. As with valproate, patients or carers should be told how to recognise signs of blood, liver, or skin disorders.

Common/very common carbamazepine side effects include but are not limited to: Dizziness; drowsiness; dry mouth; eosinophilia (overly high level of white blood cells in the bloodstream); fatigue; fluid imbalance; hyponatraemia (low blood sodium levels); leucopenia (decreased number of white blood cells in the bloodstream); nausea; oedema (swelling caused by fluid buildup in tissues); skin reactions; thrombocytopenia (blood platelet deficiency); vision disorders; and vomiting.

Lamotrigine (Lamictal®)

Lamotrigine is indicated as a first- or second-line monotherapy for generalised tonic-clonic seizures in women, girls, and people able to have children. It is also indicated as an adjunctive treatment for male and female adults and children with generalised tonic-clonic seizures, or as monotherapy or adjunctive treatment for focal seizures, absence seizures, myoclonic seizures, and for idiopathic generalised epilepsies in people able to have children. The BNF recommends that it also be used as monotherapy in people with Lennox-Gastaut syndrome.

NICE guidelines warn that lamotrigine may exacerbate symptoms in people with myoclonic seizures and those with Dravet and Lennox-Gastaut syndromes but stop short of recommending against its use in these groups.

The BNF also cautions against the use of lamotrigine in people with Parkinson’s disease, as the medication can exacerbate symptoms of the disease.

Lamotrigine (along with levetiracetam) has replaced sodium valproate and other AEDs both as a first- and second-line treatment for many epilepsies in people of childbearing potential. This follows the delayed publication of studies showing that sodium valproate causes an increased risk of birth defects and learning difficulties when taken during pregnancy. Following a 2021 safety review of ten anti-epileptic drugs for use in pregnancy, lamotrigine and levetiracetam were found to be the safest for pregnancies, with no indication of any increased risk for congenital malformations caused by in utero exposure to either drug. However, evidence of risk for developmental disorders as a result of prenatal exposure is inconclusive. A Cochrane review found lamotrigine to be an effective alternative to sodium valproate or carbamazepine in the treatment of generalised tonic-clonic seizures.

There is some documentation of skin conditions including Stevens-Johnson syndrome and toxic epidermal necrolysis arising from use of lamotrigine. These effects tend to occur at higher doses, or when lamotrigine is combined with sodium valproate.

Common/very common side effects include, but are not limited to: Aggression; joint stiffness; diarrhoea; dizziness; drowsiness; dry mouth; fatigue; nausea; skin rashes; sleep disorders; tremor; and vomiting.

Levetiracetam (Desitrend®; Keppra®)

Levetiracetam is indicated for treatment of focal seizures in adults and children as either a monotherapy or an adjunctive treatment. It can also be prescribed as an adjunctive treatment for myoclonic and tonic-clonic seizures in adults and children, or as a treatment for convulsive status epilepticus in children.

The BNF cautions against use in those who are at risk of a prolonged QT interval (the distance between the Q-wave and the T-wave on an electrocardiogram). A prolonged QT interval can lead to certain types of arrythmia, and recent research suggests that levetiracetam may contribute to a longer QT interval.

As with lamotrigine, levetiracetam is viewed as a relatively safe drug for pregnancies, making it a go-to treatment for use in people of childbearing potential. However, the manufacturer advises that breastfeeding mothers should avoid using levetiracetam, as traces of it are present in breastmilk.

Common/very common side effects include but are not limited to: Anxiety; decreased appetite; asthenia (lack of energy); depression; diarrhoea; dizziness; drowsiness; gastrointestinal discomfort; increased infection risk; mood alteration; movement disorders; nausea; skin reactions; tremor; vertigo; and vomiting.

Topiramate (Topamax®)

Topiramate is indicated for use in adults and children as monotherapy or adjunctive treatment for generalised tonic-clonic or focal seizures, or as an adjunctive treatment for seizures associated with Lennox Gastaut syndrome.

The BNF cautions that topiramate is associated with the onset of acute myopia (short sightedness) and other ophthalmic disorders. Use of topiramate should be quickly stopped and an ophthalmologist should be consulted if there are symptoms of raised intra-ocular pressure (pressure inside the eyeballs).

The manufacturer recommends that those who are pregnant should consider using alternative AEDs due to an increased associated risk of major congenital malformations in pregnancies as a result of using the drug. As of July 2022, the MHRA had begun a safety review of the use of topiramate in pregnancy following claims that children who were exposed prenatally to topiramate were born with an increased risk of autism spectrum disorders, intellectual disability, and neurodevelopmental disorders. Until the review can report its findings, those who are able to get pregnant are advised to be cautious about using topiramate. As with levetiracetam, the manufacturer advises that breastfeeding mothers avoid using topiramate.

Common/very common side effects include: Alopecia (irregular hair loss); anaemia (red blood cell deficiency); anxiety; asthenia (lack of energy); confusion; constipation; depression; diarrhoea; dizziness; drowsiness; dry mouth; fever (in children); gastrointestinal disorders; hypersensitivity; memory loss; altered mood; movement disorders; nausea; seizures; skin reactions; sleep disorders; altered sense of taste; tinnitus; tremor; urinary disorders; urolithiases (kidney stones); vertigo (in children); vomiting (in children); and weight changes.

The side effects listed above are not exhaustive. A full list of side effects, cautions, and contraindications for each of these medicines can be found within the BNF’s drug monographs (searchable by generic name), or by searching for individual brand/generic names on the Electronic Medicines Compendium (EMC) website.

For further information about the side effects of AEDs, take a look at this resource from Epilepsy Scotland.