This page covers the single and add-on anti-seizure medication options for treating generalised tonic-clonic seizures.
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Single anti-seizure medication options
The first choice of medication for generalised tonic-clonic seizures is either:
- Lamotrigine (Lamictal and other brand names),
- Levetiracetam (Keppra and other brand names), or
- Sodium valproate (Epilim and other brand names) - See information below
If one of the options does not work, the others can be tried.
Sodium valproate
In January 2024, new rules were introduced for prescribing sodium valproate.
Two specialists are now needed to approve:
- New or ongoing valproate treatments for girls and women.
- New valproate treatments for boys and men
The specialists must agree that your epilepsy does not respond to other treatments and the benefits of treatment outweigh the risks.
For girls and women, valproate can seriously harm an unborn baby when taken during pregnancy.
For boys and men, valproate may cause infertility. Some people’s fertility may return when their treatment is stopped or reduced. There is also some evidence that valproate can cause harm in the testicles of animals, but it’s unclear what this means for humans.
Never stop taking valproate before talking to your specialist first. Not taking medication as prescribed can increase the risk of a seizure.
Your epilepsy specialist will let you know when your treatment is due to be reviewed.
If you are planning a pregnancy it is important to speak to your healthcare professional as soon as possible about your treatment options.
If you have any questions or concerns about valproate, please speak to your healthcare professional.
Find out more about sodium valproate in the MHRA’s patient guide.
Find out more about Anti-seizure medications, contraception and pregnancy.
Switching from the first to second single anti-seizure medication
During the switch from the first single anti-seizure medication to the second option:
- The dose of the first anti-seizure medication remains the same while the dose of the second is increased slowly
- If the second anti-seizure medication works, the dose of the first will be slowly tapered off
If the second anti-seizure medication doesn’t work, the dose will be slowly tapered off and a third option considered
First add-on anti-seizure medication options
If single anti-seizure medications do not work, then one of the following can be tried as an add-on treatment:
- Clobazam (Frisium, Onfi and other brand names)
- Lamotrigine (Lamictal and other brand names)
- Levetiracetam (Keppra and other brand names)
- Perampanel (Fycompa)
- Sodium valproate (Epilim and other brand names) – see information above
- Topiramate (Topamax and other brand names)
Women and girls who can have children need to meet the criteria of the Pregnancy Prevention Programme.
If the first choice doesn’t work as an add-on treatment, then one of the others will be tried.
Second add-on anti-seizure medication options
If none of the above first add-on anti-seizure medications work, then the following can be tried:
- Brivaracetam (Briviact)
- Lacosamide (Vimpat and other brand names)
- Phenobarbital (Luminal and other brand names)
- Primidone (Mysoline)
- Zonisamide (Zonegran and other brand names)
If the first one tried doesn’t work as an add-on treatment, then one of the others will be tried.
Switching to using add-on anti-seizure medications
When starting an add-on treatment, the dose will be managed carefully and reviewed frequently.
This will include monitoring for side effects such as feeling sedated.
If add-on treatments don’t reduce seizures, epilepsy specialists will aim for the combination of anti-seizure medications that is the most effective while and has tolerable side effects.
Epilepsy specialists will discuss with the person, and their family or carers, as appropriate, the benefits of taking as few medicines as possible for seizure freedom or control.
Anti-seizure medications that may make seizures worse
In people with absence or myoclonic seizures, including in juvenile myoclonic epilepsy, the following anti-seizure medications may make seizures worse:
- Carbamazepine (Tegretol and other brand names)
- Gabapentin (Neurontin and other brand names)
- Lamotrigine (Lamictal and other brand names) for myoclonic seizures
- Oxcarbazepine (Trileptal and other brand names)
- Phenytoin (Dilantin and other brand names)
- Pregabalin (Lyrica and other brand names)
- Tiagabine (Gabitril)
- Vigabatrin (Sabril)
Find out more about Anti-seizure medications, contraception and pregnancy.
