Guidelines

Question 1

What does choice of anti-epileptic depend upon?

Answer 1

Medication is categorised and chosen by syndrome and seizure type

However other considerations include:
Age (some meds are unlicensed)
Gender
Child bearing potential
Co-morbidities and other medications
Experience with AEDs
Pregnancy and breastfeeding

Question 2

Who initiates AEDs medications?

Answer 2

Medications are initiated by a specialist under an Epilepsy care plan.
This involves an agreement between the patient/family/carers and primary and secondary care teams.
The patient will be

Question 3

What is the Epilepsy care plan?

Answer 3

It is an individualised care plan detailing diagnosis, treatment, care and support. It is discussed and agreed with the person and, if appropriate, their family or carers. The plan allows people to make informed choices about their epilepsy and helps to coordinate care between healthcare and other professionals in different settings (primary and secondary care teams).
This involves both the consultant and epilepsy specialist nurses.

Question 4

What is the main aim of AEDs?

Answer 4

Ideally want the patient to be seizure free on monotherapy, with limited interactions and side effects

Question 5

How should doses of AEDs be managed?

Answer 5

Initiate the patient on a low dose and gradually titrate upwards to monitor for response but also toxicity.

Question 6

What should you do if the first AED fails and the second AED fails?

Answer 6

If the first AED is insufficient/lack of response/toxicity - I think you introduce a second AED uptitrate that medication before tapering the dose of the first AED to ensure some epileptic control. However I think this may depend upon the circumstances in which the first AED has been stopped.
If the second AED fails, you then tend to use combination therapy of multiple AEDs.

Question 7

What is the purpose of regular therapeutic drug monitoring of AEDs?

Answer 7

Depending on the type of AED, specialist may request regular blood tests.
These are used to:
Explore toxicity
Identify non-adherence
Adjustment of Phenytoin
Managing interactions with other drugs
For specific clinical conditions

Question 8

What is the first line treatment for generalised tonic-clonic seizures?

Answer 8

First line monotherapy of sodium valproate in:
Boys and men
Girls aged under 10 years and who are unlikely to need treatment when they are old enough to have children
Women who are unable to have children

Offer Lamotrigine or Levetiracetam as first line monotherapy in:
Women and girls of a child bearing age including girls who are likely to need treatment when they are old enough to have children.

Question 9

What is the second line monotherapy for generalised tonic-clonic seizures?

Answer 9

If sodium valproate was unsuccessful as first line monotherapy offer Lamotrigine or Levetiracetam as second line monotherapy.

If Levetiracetam or Lamotrigine was unsuccessful as first line monotherapy, try the other.

Question 10

What are the first-line add on treatments for generalised tonic-clonic seizures?

Answer 10

If monotherapy is unsuccessful in people with generalised tonic-clonic seizures, consider 1 of the following first-line add-on treatment options:
-Clobazam
-Lamotrigine
-Levetiracetam
-Perampanel
-Sodium valproate, except in women and girls able to have children
-Topiramate.

If the first choice is unsuccessful, consider the other first-line add-on options.

Question 11

If the first line add on are unsuccessful in generalised tonic-clonic seizures what are the second line add on?

Answer 11

Consider one of the following second line treatment add on:
-Brivaracetam
-Lacosamide
-Phenobarbital
-Primidone
-Zonisamide

If the first choice is unsuccessful, consider the other second-line add-on options

Question 12

What is the first line choice for patients with focal seizures?

Answer 12

First-line monotherapy for focal seizures should be Levetiracetam or Lamotrigine. If one of these are unsuccessful the other should be considered.

Question 13

What are the second line monotherapy for focal seizures?

Answer 13

If the first line monotherapy for focal seizures are unsuccessful, consider 1 of the following second-line monotherapy options:
-Carbamazepine
-Oxcarbazepine
-Zonisamide.

If the first choice is unsuccessful, consider the other second-line monotherapy options.

Question 14

What is the third line monotherapy for focal seizures?

Answer 14

If second-line monotherapies tried are unsuccessful in people with focal seizures, consider lacosamide as third-line monotherapy.

Question 15

What are the first line add on for focal seizures?

Answer 15

If monotherapy is unsuccessful in people with focal seizures, consider one of the following first-line add on:
-Carbamazepine
-Lacosamide
-Lamotrigine
-Levetiracetam
-Oxcarbazepine
-Topiramate
-Zonisamide.

If the first choice is unsuccessful, consider the other first-line add-on options.

Question 16

What are the second line add on for focal seizures?

Answer 16

If first-line add-on treatments tried are unsuccessful in people with focal seizures, consider 1 of the following second-line add-on treatment options:
-Brivaracetam
-Cenobamate
-Eslicarbazepine acetate
-Perampanel
-Pregabalin
-Sodium valproate, except in women and girls able to have children.

If the first choice is unsuccessful, consider the other second-line add-on options

Question 17

What are the third line add on for focal seizures?

Answer 17

If second-line add on are insufficient, consider one of the third line add on therapies:
Phenobarbital
Phenytoin
Tiagabine
Vigabatrin.

If the first choice is unsuccessful, consider the other third-line add-on options

Question 18

What is the first line monotherapy for absence seizures (inc childhood absence seizures)?

Answer 18

Ethosuximide

Question 19

What is the second and third line monotherapy for absence seizures?

Answer 19

Sodium valproate can be offered as second line / add on therapy in:
Boys and men
Girls under 10 unlikely to need treatment when they are old enough to have children
Women who can’t have children

If second-line treatment is unsuccessful for absence seizures, consider lamotrigine or levetiracetam as a third-line monotherapy or add-on treatment options.
(This would be considered second line for women and girls of child bearing potential, or girls under 10 likely to need treatment when they are old enough to have children).

If the first choice is unsuccessful, consider the other of these options

Question 20

Which anti-seizure medication can exacerbate absence and myoclonic seizures and therefore should be avoided in patients with this type?

Answer 20

Carbamazepine
Gabapentin
Oxcarbazepine
Phenobarbital
Phenytoin
Pregabalin
Tiagabine
Vigabatrin

Lamotrigine may also exacerbate myoclonic seizures

Question 21

What is the first line monotherapy for absence seizure with other seizure types?

Answer 21

Sodium valproate should be consider first-line monotherapy for absence seizures with other types (or those at risk) in:
Boys and men
Girls aged under 10 years and who are unlikely to need treatment when they are old enough to have children
Women who are unable to have children

Lamotrigine or Levetiracetam should be considered first-line monotherapy in women and children of childbearing potential and girls under 10 likely to need treatment when they are old enough to have children.
If the first choice is unsuccessful, consider the other of these options.

Question 22

What is the second line treatment for absence seizure with other seizure types?

Answer 22

If first-line treatments tried are unsuccessful for absence seizures and other seizure types (or at risk of these), consider:

-Lamotrigine or levetiracetam as a second-line monotherapy or add-on treatment options or

-Ethosuximide as a second-line add-on treatment.

If the first choice is unsuccessful, consider the other second-line options.

Question 23

What is the first line treatment for myoclonic seizures?

Answer 23

Sodium valproate should be offered as first line treatment for myoclonic seizures in:
Boys and men
Girls aged under 10 years and who are unlikely to need treatment when they are old enough to have children
Women who are unable to have children

Levetiracetam should be offered as first line treatment for myoclonic seizures:
Women and girls and girls under 10 who will need treatment when they are old enough to have children

Question 24

What is the second line treatment for myoclonic seizures?

Answer 24

If sodium valproate is unsuccessful as first line treatment, offer Levetiracetam as second line monotherapy or as add on

Question 25

If Levetiracetam is unsuccessful for use in myoclonic seizures what should be considered?

Answer 25

If levetiracetam is unsuccessful for myoclonic seizures, consider 1 of the following as monotherapy or add-on treatment options:
-Brivaracetam
-Clobazam
-Clonazepam
-Lamotrigine
-Phenobarbital
-Piracetam
-Topiramate
-Zonisamide

If the first choice is unsuccessful consider any of these other options.

Question 26

What is the first line treatment in tonic or atonic seizures?

Answer 26

Offer sodium valproate as first-line treatment for tonic or atonic seizures in:
Boys and men
Girls aged under 10 years and who are unlikely to need treatment when they are old enough to have children
Women who are unable to have children.

Consider lamotrigine as first-line treatment for tonic or atonic seizures in women and girls able to have children (including young girls who are likely to need treatment when they are old enough to have children).

Question 27

What are the second/third line treatments for tonic or atonic seizures?

Answer 27

If sodium valproate monotherapy is unsuccessful as first line therapy, consider Lamotrigine as second line monotherapy or add on treatment.

If Lamotrigine is unsuccessful for treating tonic or atonic seizures, consider one of the following:
Clobazam
Rufinamide
Topiramate

If the first choice is unsuccessful, consider any other of these options

Question 28

What are the further treatment options for tonic or atonic seizures?

Answer 28

If third-line treatment is unsuccessful for tonic or atonic seizures in children, consider a ketogenic diet as an add-on treatment under the supervision of a ketogenic diet team.

If all other treatment options for tonic or atonic seizures are unsuccessful, consider felbamate as an add-on treatment under the supervision of a neurologist with expertise in epilepsy.

Question 29

Which anti-seizure medication can exacerbate tonic or atonic seizures?

Answer 29

Carbamazepine
Gabapentin
Oxcarbazepine
Pregabalin
Tiagabine
Vigabatrin

Question 30

What is the first line treatment for idiopathic generalised epilepsies?

Answer 30

Offer sodium valproate as first-line treatment for idiopathic generalised epilepsies in:
Boys and men
Girls aged under 10 years and who are unlikely to need treatment when they are old enough to have children
Women who are unable to have children

Levetiracetam or Lamotrigine should be offered as first line therapy in women and girls and girls under 10 who are likely to need treatment when they are old enough to have children.
If the first choice is unsuccessful for idiopathic generalised epilepsies, offer the other of these options.

Question 31

What is the second line treatment for idiopathic generalised epilepsies?

Answer 31

If the first line is unsuccessful (sodium valproate) consider lamotrigine or levetiracetam as a second-line monotherapy or add-on treatment options. If the first choice is unsuccessful, consider the other of these options.

Question 32

What is the third line treatment for idiopathic generalised epilepsies?

Answer 32

If second-line treatments tried are unsuccessful for idiopathic generalised epilepsies, consider perampanel or topiramate as third-line add-on treatment options. If the first choice is unsuccessful, consider the other of these options

Question 33

What is a long-term risk associated with AED use?

Answer 33

Increased risk of bone loss, reduced bone density and the risk of osteoporosis and fractures is also higher in epilepsy as a result of injuries sustained during seizures.

Possibly due to AEDs inducing CYP450 enzymes responsible for Vitamin D metabolism.

Question 34

Which AEDs in particular have been identified as having a particular increased risk of mineral bone density loss?

Answer 34

Enzyme inducers:
Carbamazepine
Phenytoin
Primidone

Non-enzyme inducers:
Sodium Valproate

Vitamin D levels should be monitored in all of the above medications when used.
It is also important to note that risk to bone health has not been extensively studied in the newer AEDs.

Question 35

What is the appropriate management for mitigating reduced mineral bone density loss?

Answer 35

Monitoring the bones with DEXA scans and fracture risk assessment tools
Sufficient Calcium and Vitamin D within the diet
Encouraging sun exposure and exercise specifically strengthening activities - if insufficient Vitamin D supplementation may be required
Lifestyle advice such as smoking cessation and reducing alcohol intake as this is linked to osteoporosis and increased likelihood of fractures.

Question 36

When is the risk to bone health the greatest in AED use?

Answer 36

Using multiple AEDs for long periods of time.

Question 37

What are two general key side effects of AEDs?

Answer 37

Risk of suicidal thoughts and behaviours associated with AEDs
Anti-epileptic hypersensivity syndrome

Question 38

Which AEDs specifically are associated with adverse psychiatric effects?

Answer 38

AEDs with GABAergic properties include the barbiturates, the benzodiazepines, tiagabine, vigabatrin, topiramate, zonisamide, and gabapentin.
The rise in depression and, in particular, in suicidal behavior has been attributed to a GABAergic-mediated decrease in serotonin secretion at the raphe nuclei.
However non-GABAergic AEDs such as Levetiracetam has also been associated with increased psychiatric effects.

Question 39

What is anti-epileptic hypersensitivity syndrome?

Answer 39

Rare but potentially fatal adverse drug reaction which can occur 1-8 weeks of exposure to an AED. The syndrome is defined by the triad of fever, skin rash, and internal organ involvement.

Question 40

Which AEDs are more commonly associated with anti-epileptic hypersensitivity syndrome?

Answer 40

Phenytoin
Phenobarbital
Carbamazepine (and potentially pro-drugs)
Primidone?