Appendix E: Pharmacological treatment

Appendix E: Pharmacological treatment

The tables that follow provide a summary reference guide to pharmacological treatment. They were updated in 2011. Licensing details are listed under table 3. All drugs are listed in alphabetical order.

Table 1 AED options by seizure type

Seizure type

First-line AEDs

Adjunctive AEDs

Other AEDs that may be considered on referral to tertiary care

Do not offer AEDs (may worsen seizures)

Generalised tonic–clonic

Carbamazepine

Lamotrigine

Oxcarbazepinea

Sodium valproate

Clobazama

Lamotrigine

Levetiracetam

Sodium valproate

Topiramate

(If there are absence or myoclonic seizures, or if JME suspected)

Carbamazepine

Gabapentin

Oxcarbazepine

Phenytoin

Pregabalin

Tiagabine

Vigabatrin

Tonic or atonic

Sodium valproate

Lamotriginea

Rufinamidea

Topiramatea

Carbamazepine

Gabapentin

Oxcarbazepine

Pregabalin

Tiagabine

Vigabatrin

Absence

Ethosuximide

Lamotriginea

Sodium valproate

Ethosuximide

Lamotriginea

Sodium valproate

Clobazama

Clonazepam

Levetiracetama

Topiramatea

Zonisamidea

Carbamazepine

Gabapentin

Oxcarbazepine

Phenytoin

Pregabalin

Tiagabine

Vigabatrin

Myoclonic

Levetiracetama

Sodium valproate

Topiramatea

Levetiracetam

Sodium valproate

Topiramatea

Clobazama

Clonazepam

Piracetam

Zonisamidea

Carbamazepine

Gabapentin

Oxcarbazepine

Phenytoin

Pregabalin

Tiagabine

Vigabatrin

Focal

Carbamazepine

Lamotrigine

Levetiracetam

Oxcarbazepine

Sodium valproate

Carbamazepine

Clobazama

Gabapentina

Lamotrigine

Levetiracetam

Oxcarbazepine

Sodium valproate

Topiramate

Eslicarbazepine acetatea

Lacosamide

Phenobarbital

Phenytoin

Pregabalina

Tiagabine

Vigabatrin

Zonisamidea

Prolonged or repeated seizures and convulsive status epilepticus in the community

Buccal midazolam

Rectal diazepamb

Intravenous lorazepam

Convulsive status epilepticus in hospital

Intravenous lorazepam

Intravenous diazepam

Buccal midazolam

Intravenous phenobarbital

Phenytoin

Refractory convulsive status epilepticus

Intravenous midazolamb

Propofolb (not in children)

Thiopental sodiumb

a At the time of publication (January 2012) this drug did not have UK marketing authorisation for this indication and/or population (see table 3 for specific details about this drug for this indication and population). Informed consent should be obtained and documented.

b At the time of publication (January 2012), this drug did not have UK marketing authorisation for this indication and/or population (see table 3 for specific details about this drug for this indication and population). Informed consent should be obtained and documented in line with normal standards in emergency care.

Table 2 AED options by epilepsy syndrome

Epilepsy syndrome

First-line AEDs

Adjunctive AEDs

Other AEDs that may be considered on referral to tertiary care

Do not offer AEDs
(may worsen seizures)

Childhood absence epilepsy or other absence syndromes

Ethosuximide

Lamotriginea

Sodium valproate

Ethosuximide

Lamotriginea

Sodium valproate

Clobazama

Clonazepam

Levetiracetama

Topiramatea

Zonisamidea

Carbamazepine

Gabapentin

Oxcarbazepine

Phenytoin

Pregabalin

Tiagabine

Vigabatrin

Juvenile absence epilepsy or other absence syndromes

Ethosuximide

Lamotriginea

Sodium valproate

Ethosuximide

Lamotriginea

Sodium valproate

Clobazama

Clonazepam

Levetiracetama

Topiramatea

Zonisamidea

Carbamazepine

Gabapentin

Oxcarbazepine

Phenytoin

Pregabalin

Tiagabine

Vigabatrin

Juvenile myoclonic epilepsy

Lamotriginea

Levetiracetama

Sodium valproate

Topiramatea

Lamotriginea

Levetiracetam

Sodium valproate

Topiramatea

Clobazama

Clonazepam

Zonisamidea

Carbamazepine

Gabapentin

Oxcarbazepine

Phenytoin

Pregabalin

Tiagabine

Vigabatrin

Epilepsy with generalised tonic–clonic seizures only

Carbamazepine

Lamotrigine

Oxcarbazepinea

Sodium valproate

Clobazama

Lamotrigine

Levetiracetam

Sodium valproate

Topiramate

Idiopathic generalised epilepsy

Lamotriginea

Sodium valproate

Topiramatea

Lamotriginea

Levetiracetama

Sodium valproate

Topiramatea

Clobazama

Clonazepam

Zonisamidea

Carbamazepine

Gabapentin

Oxcarbazepine

Phenytoin

Pregabalin

Tiagabine

Vigabatrin

Infantile spasms not due to tuberous sclerosis

Discuss with, or refer to, a tertiary paediatric epilepsy specialist

Steroid (prednisolone or tetracosactidea) or vigabatrin

Infantile spasms due to tuberous sclerosis

Discuss with, or refer to, a tertiary paediatric epilepsy specialist

Vigabatrin or steroid (prednisolone or tetracosactidea)

Benign epilepsy with centrotemporal spikes

Carbamazepinea

Lamotriginea

Levetiracetama

Oxcarbazepinea

Sodium valproate

Carbamazepinea

Clobazama

Gabapentina

Lamotriginea

Levetiracetama

Oxcarbazepinea

Sodium valproate

Topiramatea

Eslicarbazepine acetatea

Lacosamidea

Phenobarbital

Phenytoin

Pregabalina

Tiagabinea

Vigabatrina

Zonisamidea

Panayiotopoulos syndrome

Carbamazepinea

Lamotriginea

Levetiracetama

Oxcarbazepinea

Sodium valproate

Carbamazepinea

Clobazama

Gabapentina

Lamotriginea

Levetiracetama

Oxcarbazepinea

Sodium valproate

Topiramatea

Eslicarbazepine acetatea

Lacosamidea

Phenobarbital

Phenytoin

Pregabalina

Tiagabinea

Vigabatrina

Zonisamidea

Late-onset childhood occipital epilepsy (Gastaut type)

Carbamazepinea

Lamotriginea

Levetiracetama

Oxcarbazepinea

Sodium valproate

Carbamazepinea

Clobazama

Gabapentina

Lamotriginea

Levetiracetama

Oxcarbazepinea

Sodium valproate

Topiramatea

Eslicarbazepine acetatea

Lacosamidea

Phenobarbital

Phenytoin

Pregabalina

Tiagabinea

Vigabatrina

Zonisamidea

Dravet syndrome

Discuss with, or refer to, a tertiary paediatric epilepsy specialist

Sodium valproate

Topiramatea

Clobazama

Stiripentol

Carbamazepine

Gabapentin

Lamotrigine

Oxcarbazepine

Phenytoin

Pregabalin

Tiagabine

Vigabatrin

Continuous spike and wave during slow sleep

Refer to a tertiary paediatric epilepsy specialist

Lennox–Gastaut syndrome

Discuss with, or refer to, a tertiary paediatric epilepsy specialist

Sodium valproate

Lamotrigine

Felbamatea

Rufinamide

Topiramate

Carbamazepine

Gabapentin

Oxcarbazepine

Pregabalin

Tiagabine

Vigabatrin

Landau–Kleffner syndrome

Refer to a tertiary paediatric epilepsy specialist

Myoclonic-astatic epilepsy

Refer to a tertiary paediatric epilepsy specialist

a At the time of publication (January 2012), this drug did not have UK marketing authorisation for this indication and/or population (please see table 3 for specific details about this drug for this indication and population). Informed consent should be obtained and documented.

Licensing indications

Detailed below are drugs that have been recommended but that do not currently have licensed indications for these seizures types or syndromes or particular populations.

Table 3 Licensing indications of the guideline AEDs

Seizure type/syndrome

Drug

Details of licensing

Treatment of refractory focal seizures

Clobazam

At the time of publication, clobazam did not have UK marketing authorisation for use in children younger than 3 years (BNFC). There was insufficient experience of the use of this drug in children younger than 6 years to enable any dosage recommendation to be made (SPC). It did have authorisation for adjunctive therapy for epilepsy, monotherapy under specialist supervision for catamenial (menstruation) seizures (usually for 7–10 days each month, just before and during menstruation), and cluster seizures (BNFC).

Eslicarbazepine acetate

At the time of publication, eslicarbazepine acetate did not have UK marketing authorisation for use in children younger than 18 years. It was not recommended owing to a lack of data on safety and efficacy (SPC).

Gabapentin

At the time of publication, gabapentin did not have UK marketing authorisation for use in children younger than 6 years and at doses over 50 mg/kg daily in children younger than 12 years (BNFC). The use of gabapentin was not recommended in children younger than 6 years owing to the lack of sufficient supporting data (SPC).

Pregabalin

At the time of publication, pregabalin did not have UK marketing authorisation for use in children (BNF). Pregabalin was not recommended for use in children younger than 12 years and adolescents (12–17 years) owing to insufficient data on safety and efficacy (SPC).

Zonisamide

At the time of publication, zonisamide did not have UK marketing authorisation for use in children younger than 18 years owing to insufficient data on safety and efficacy (SPC).

GTC seizures

Clobazam

At the time of publication, clobazam did not have UK marketing authorisation for use in children younger than 3 years (BNFC). There was insufficient experience of the use of this drug in children younger than 6 years to enable any dosage recommendation to be made (SPC). It did have authorisation for adjunctive therapy for epilepsy, monotherapy under specialist supervision for catamenial (menstruation) seizures (usually for 7–10 days each month, just before and during menstruation), and cluster seizures (BNFC).

Oxcarbazepine

At the time of publication, oxcarbazepine did not have UK marketing authorisation for GTC seizures (BNF). It had authorisation for focal seizures with or without secondary GTC seizures (BNF).

Absence seizures

Clobazam

At the time of publication, clobazam did not have UK marketing authorisation for use in children younger than 3 years (BNFC). There was insufficient experience of the use of this drug in children younger than 6 years to enable any dosage recommendation to be made (SPC). It did have authorisation for adjunctive therapy for epilepsy, monotherapy under specialist supervision for catamenial (menstruation) seizures (usually for 7–10 days each month, just before and during menstruation), and cluster seizures (BNFC).

Lamotrigine

At the time of publication, lamotrigine had UK marketing authorisation for monotherapy of typical absence seizures for those aged 2–12 years only. There was not authorisation outside of this age range (BNF).

Levetiracetam

At the time of publication, levetiracetam did not have UK marketing authorisation for use in absence seizures. It had authorisation for monotherapy and adjunctive treatment of focal seizures with or without secondary generalisation and adjunctive therapy of myoclonic seizures in patients with JME and GTC seizures (BNF).

Topiramate

At the time of publication, topiramate did not have UK marketing authorisation for use in absence seizures. It had authorisation for monotherapy and adjunctive treatment of focal seizures and GTC seizures and adjunctive treatment for seizures associated with Lennox–Gastaut syndrome (BNF).

Zonisamide

At the time of publication, zonisamide did not have UK marketing authorisation for use in absence seizures. It had authorisation for adjunctive therapy for adult patients with refractory focal seizures, with or without secondary generalisation (BNF).

Myoclonic seizures

Clobazam

At the time of publication, clobazam did not have UK marketing authorisation for use in children younger than 3 years (BNFC). There was insufficient experience of the use of this drug in children younger than 6 years to enable any dosage recommendation to be made (SPC). It did have authorisation for adjunctive therapy for epilepsy, monotherapy under specialist supervision for catamenial (menstruation) seizures (usually for 7–10 days each month, just before and during menstruation), and cluster seizures (BNFC).

Levetiracetam

At the time of publication, levetiracetam did not have UK marketing authorisation for monotherapy use in myoclonic seizures. It had authorisation for monotherapy and adjunctive treatment of focal seizures with or without secondary generalisation and adjunctive therapy of myoclonic seizures in patients with JME and GTC seizures (BNF).

Topiramate

At the time of publication, topiramate did not have UK marketing authorisation for use in myoclonic seizures. It had authorisation for monotherapy and adjunctive treatment of focal seizures and GTC seizures and adjunctive treatment for seizures associated with Lennox–Gastaut syndrome (BNF).

Zonisamide

At the time of publication, zonisamide did not have UK marketing authorisation for use in myoclonic seizures. It had authorisation for use in adjunctive treatment of refractory focal seizures with or without secondary generalisation (BNF).

Tonic or atonic seizures

Lamotrigine

At the time of publication, lamotrigine did not have UK marketing authorisation for use in tonic or atonic seizures. It had authorisation for monotherapy and adjunctive treatment of focal seizures, GTC seizures and seizures associated with Lennox–Gastaut syndrome. It also had authorisation for monotherapy of typical absence seizures for children aged 2–12 years (BNF, BNFC).

Rufinamide

At the time of publication, rufinamide did not have UK marketing authorisation for use in tonic or atonic seizures. It had authorisation for the adjunctive treatment of seizures associated with Lennox–Gastaut syndrome (BNF).

Topiramate

At the time of publication, topiramate did not have UK marketing authorisation for use in tonic or atonic seizures. It had authorisation for monotherapy and adjunctive treatment of focal seizures and GTC seizures and adjunctive treatment for seizures associated with Lennox–Gastaut syndrome (BNF).

Infantile spasms

ACTH (tetracosactide)

At the time of publication, ACTH (tetracosactide) did not have UK marketing authorisation for infantile spasms. Depot ampoules are not recommended in infants and children younger than 3 years owing to the presence of benzyl alcohol in the formulation (SPC).

Lennox–Gastaut syndrome

Felbamate

At the time of publication, felbamate did not have UK marketing authorisation. There was no SPC available.

Dravet syndrome

Clobazam

At the time of publication, clobazam did not have UK marketing authorisation for use in children under 3 years of age (BNFC). There was insufficient experience of the use of this drug in children younger than 6 years to enable any dosage recommendation to be made (SPC). It did have authorisation for adjunctive therapy for epilepsy, monotherapy under specialist supervision for catamenial (menstruation) seizures (usually for 7–10 days each month, just before and during menstruation), and cluster seizures (BNFC).

Topiramate

At the time of publication, topiramate did not have UK marketing authorisation for use in Dravet syndrome. It had authorisation for monotherapy and adjunctive treatment of focal seizures and GTC seizures and adjunctive treatment for seizures associated with Lennox–Gastaut syndrome (BNF).

BECTS/Panayiotopoulos syndrome and late-onset childhood occipital epilepsy (Gastaut type)

Carbamazepine

At the time of publication, carbamazepine did not have UK marketing authorisation for BECTS/Panayiotopoulos syndrome and late-onset childhood occipital epilepsy (Gastaut type). It had authorisation for focal and GTC seizures (BNF).

Clobazam

At the time of publication, clobazam did not have UK marketing authorisation for use in children younger than 3 years (BNFC). There was insufficient experience of the use of this drug in children younger than 6 years to enable any dosage recommendation to be made (SPC). It did have authorisation for adjunctive therapy for epilepsy, monotherapy under specialist supervision for catamenial (menstruation) seizures (usually for 7–10 days each month, just before and during menstruation), and cluster seizures (BNFC).

Eslicarbazepine acetate

At the time of publication, eslicarbazepine acetate did not have UK marketing authorisation for use in children younger than 18 years. It was not recommended owing to a lack of data on safety and efficacy (SPC).

Gabapentin

At the time of publication, gabapentin did not have UK marketing authorisation for BECTS/Panayiotopoulos syndrome and late-onset childhood occipital epilepsy (Gastaut type). It had authorisation for use in focal seizures with and without secondary generalisation (BNF) but it did not have UK marketing authorisation for use in children younger than 6 years and at doses over 50 mg/kg daily in children younger than 12 years (BNFC). The use of gabapentin was not recommended in children younger than 6 years owing to the lack of sufficient supporting data (SPC).

Lacosamide

At the time of publication, lacosamide did not have UK marketing authorisation for BECTS/Panayiotopoulos syndrome and late-onset childhood occipital epilepsy (Gastaut type). It had authorisation for adjunctive treatment of focal seizures with or without secondary generalisation (BNF).

Lamotrigine

At the time of publication, lamotrigine did not have UK marketing authorisation for BECTS/Panayiotopoulos syndrome and late-onset childhood occipital epilepsy (Gastaut type). It had authorisation for monotherapy and adjunctive treatment of focal and GTC seizures, seizures associated with Lennox–Gastaut syndrome, and monotherapy treatment of typical absence seizures in children aged 2 to 12 years (BNF).

Levetiracetam

At the time of publication, levetiracetam did not have UK marketing authorisation for BECTS/Panayiotopoulos syndrome and late-onset childhood occipital epilepsy (Gastaut type). It had authorisation for monotherapy and adjunctive treatment of focal seizures with or without secondary generalisation and adjunctive therapy of myoclonic seizures in patients with JME and GTC seizures (BNFC).

Oxcarbazepine

At the time of publication, oxcarbazepine did not have UK marketing authorisation for BECTS/Panayiotopoulos syndrome and late-onset childhood occipital epilepsy (Gastaut type). It had authorisation for focal seizures with or without secondary GTC seizures (BNF).

Pregabalin

At the time of publication, pregabalin did not have UK marketing authorisation for use in children (BNF). Pregabalin was not recommended for use in children younger than 12 years and adolescents (12–17 years) owing to insufficient data on safety and efficacy (SPC).

Tiagabine

At the time of publication, tiagabine did not have UK marketing authorisation for BECTS/Panayiotopoulos syndrome and late-onset childhood occipital epilepsy (Gastaut type). It had authorisation for focal seizures with or without secondary generalisation that are not satisfactorily controlled by other antiepileptics (BNF).

Topiramate

At the time of publication, topiramate did not have UK marketing authorisation for BECTS/Panayiotopoulos syndrome and late-onset childhood occipital epilepsy (Gastaut type). It had authorisation for monotherapy and adjunctive treatment of focal seizures and GTC seizures and adjunctive treatment for seizures associated with Lennox–Gastaut syndrome (BNF).

Vigabatrin

At the time of publication, vigabatrin did not have UK marketing authorisation for BECTS/Panayiotopoulos syndrome. It can be prescribed in combination with other epileptic treatment for focal epilepsy with or without secondary generalisation (BNF).

Zonisamide

At the time of publication, zonisamide did not have UK marketing authorisation for BECTS/Panayiotopoulos syndrome and late-onset childhood occipital epilepsy (Gastaut type). It had authorisation for adjunctive therapy for adult patients with refractory focal seizures, with or without secondary generalisation (BNF).

IGE

Clobazam

At the time of publication, clobazam did not have UK marketing authorisation for use in children younger than 3 years (BNFC). There was insufficient experience of the use of this drug in children younger than 6 years to enable any dosage recommendation to be made (SPC). It did have authorisation for adjunctive therapy for epilepsy, monotherapy under specialist supervision for catamenial (menstruation) seizures (usually for 7–10 days each month, just before and during menstruation), and cluster seizures (BNFC).

Lamotrigine

At the time of publication, lamotrigine did not have UK marketing authorisation for use in IGE. It had authorisation for monotherapy and adjunctive treatment of focal and GTC seizures, seizures associated with Lennox–Gastaut syndrome, and monotherapy treatment of typical absence seizures in children aged 2 to 12 years (BNF).

Levetiracetam

At the time of publication, levetiracetam did not have UK marketing authorisation for IGE. It had authorisation for monotherapy and adjunctive treatment of focal seizures with or without secondary generalisation and adjunctive therapy of myoclonic seizures in patients with JME and GTC seizures (BNF).

Topiramate

At the time of publication, topiramate did not have UK marketing authorisation for use in IGE. It had authorisation for monotherapy and adjunctive treatment of focal seizures and GTC seizures and adjunctive treatment for seizures associated with Lennox–Gastaut syndrome (BNF).

Zonisamide

At the time of publication, zonisamide did not have UK marketing authorisation for use in IGE. It had authorisation for adjunctive therapy for adult patients with refractory focal seizures, with or without secondary generalisation (BNF).

JME

Clobazam

At the time of publication, clobazam did not have UK marketing authorisation for use in children younger than 3 years (BNFC). There was insufficient experience of the use of this drug in children younger than 6 years to enable any dosage recommendation to be made (SPC). It did have authorisation for adjunctive therapy for epilepsy, monotherapy under specialist supervision for catamenial (menstruation) seizures (usually for 7–10 days each month, just before and during menstruation), and cluster seizures (BNFC).

Lamotrigine

At the time of publication, lamotrigine did not have UK marketing authorisation for use in juvenile myoclonic epilepsy. It had authorisation for monotherapy and adjunctive treatment of focal and GTC seizures, seizures associated with Lennox–Gastaut syndrome, and monotherapy treatment of typical absence seizures in children aged 2 to 12 years (BNF).

Levetiracetam

At the time of publication, levetiracetam did not have UK marketing authorisation for monotherapy use in JME. It had authorisation for monotherapy and adjunctive treatment of focal seizures with or without secondary generalisation and adjunctive therapy of myoclonic seizures in patients with JME and GTC seizures (BNF).

Topiramate

At the time of publication, topiramate did not have UK marketing authorisation for use in JME. It had authorisation for monotherapy and adjunctive treatment of focal seizures and GTC seizures and adjunctive treatment for seizures associated with Lennox–Gastaut syndrome (BNF).

Zonisamide

At the time of publication, zonisamide did not have UK marketing authorisation for use in JME. It had authorisation for adjunctive therapy for adult patients with refractory focal seizures, with or without secondary generalisation (BNF).

Absence syndromes

Clobazam

At the time of publication, clobazam did not have UK marketing authorisation for use in children younger than 3 years (BNFC). There was insufficient experience of the use of this drug in children younger than 6 years to enable any dosage recommendation to be made (SPC). It did have authorisation for adjunctive therapy for epilepsy, monotherapy under specialist supervision for catamenial (menstruation) seizures (usually for 7–10 days each month, just before and during menstruation), and cluster seizures (BNFC).

Lamotrigine

At the time of publication, lamotrigine had UK marketing authorisation for monotherapy of typical absence seizures for those aged 2–12 years only. There was no authorisation outside this age range (BNF).

Levetiracetam

At the time of publication, levetiracetam did not have UK marketing authorisation for use in absence syndromes. It had authorisation for monotherapy and adjunctive treatment of focal seizures with or without secondary generalisation and adjunctive therapy of myoclonic seizures in patients with JME and GTC seizures (BNF).

Topiramate

At the time of publication, topiramate did not have UK marketing authorisation for use in absence syndromes. It had authorisation for monotherapy and adjunctive treatment of focal seizures and GTC seizures and adjunctive treatment for seizures associated with Lennox–Gastaut syndrome (BNF).

Zonisamide

At the time of publication, zonisamide did not have UK marketing authorisation for use in absence syndromes. It had authorisation for adjunctive therapy for adult patients with refractory focal seizures, with or without secondary generalisation (BNF).

Status epilepticus

Propofol

At the time of publication, propofol did not have UK marketing authorisation for status epilepticus but had authorisation for anaesthesia and sedation. Diprivan 2%, Propofol-Lipuro 2%, and Propoven 2% were not licensed for use in children younger than 3 years; Diprofusor TCI ('target controlled infusion') system was not licensed for use in children (BNFC).

Thiopental sodium

At the time of publication, thiopental sodium did not have UK marketing authorisation for status epilepticus (only if other measures fail, see section 4.8.2 in BNF), by slow intravenous injection (BNF). It is authorised for convulsive states: 75 to 125 mg (3 to 5 ml of a 2.5% solution) given by intravenous infusion (SPC).

Midazolam

At the time of publication, midazolam injection did not have UK marketing authorisation for status epilepticus (BNF, BNFC).

Diazepam

At the time of publication, diazepam did not have UK marketing authorisation for the use of Rectubes and Stesolid Rectal Tubes in children younger than 1 year (BNFC).

Abbreviations: BECTS, benign epilepsy with centrotemporal spikes; BNF, British national formulary; BNFC, British national formulary for children; GTC, generalised tonic–clonic; IGE, idiopathic generalised epilepsy; JME, juvenile myoclonic epilepsy; SPC, summary of product characteristics.

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