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Drugs Used in Epilepsy

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Sodium Valproate

Mechanism of action

Not fully understood, but is thought to be involved in reducing GABA metabolism and increasing GABAergic neurotransmission, leading to increased inhibitory activity.

Adverse effects

  • Teratogenicity – increased risk of neural tube defects
    • Do not give to patients of childbearing potential/pregnant patients
  • P450 inhibition
  • Hyponatraemia
  • Intense nausea
  • Lethargy and confusion
  • Weight gain
  • Alopecia – the hair may regrow curly
  • Movement disorders e.g. ataxia
  • Leukopenia
  • Thrombocytopenia
  • Pancreatitis
  • Increased risk of suicidal thoughts and behaviour when initiating treatment

Contraindications

  • Active liver disease
  • Acute porphyria
  • People who are of childbearing potential/pregnant

Cautions

  • Patients should be safety-netted on the signs and symptoms of the following and should seek immediate help should they arise:
    • Haematological disorders – Unexplained bruising/bleeding/sore throat/fever
    • Liver disorders
    • Pancreatitis

Monitoring

  • LFTs and BMI are usually weighed before treatment
  • LFTs, BMI, and FBC are usually measured 6 months after treatment, and then every 12 months after
  • Valproate levels themselves are not routinely monitored unless there is:
    • Evidence of ineffectiveness
    • Poor compliance
    • Toxicity is suspected

Carbamazepine

Mechanism of action

Not fully understood, it is thought to bind to voltage-gated sodium ion channels and inhibit their firing, reducing seizure activity. 

Adverse effects

  • P450 inducer
  • Vomiting
  • Sedation
  • Dizziness
  • Ataxia
  • Urticaria
  • Stevens-Johnson syndrome
  • Hyponatraemia
  • Myelosuppression – agranulocytosis/leukopenia
  • Small increased risk of suicidal thoughts and behaviour when initiating treatment

Contraindications

  • Known hypersensitivity to structurally-similar drugs e.g. tricyclic antidepressants
  • Heart blocks
  • History of bone marrow suppression
  • Taking monoamine oxidase inhibitors
  • May worsen absence and myoclonic seizures

Cautions

  • Patients should be safety-netted on the signs and symptoms of myelosuppression and should seek immediate help should they arise. These may be:
    • Unexplained bruising
    • Unexplained bleeding
    • Sore throat
    • Fever
  • Patients should seek immediate help if they develop rashes, especially if they are severe with flushing, blisters, or ulcers – these can be signs of Stevens-Johnson syndrome

Monitoring

  • FBC before treatment and periodically thereafter
    • To look for myelosuppression
  • LFTs before treatment and periodically thereafter
  • Carbamazepine levels themselves are not routinely monitored unless there is:
    • Evidence of ineffectiveness
    • Poor compliance
    • Toxicity is suspected

Lamotrigine

Mechanism of action

Not fully understood, thought to work by inhibiting sodium channel firing and inhibiting the release of glutamate.

Adverse effects

  • Stevens-Johnson syndrome and other skin rashes – withdraw immediately if they arise
  • Myelosuppression
  • Nausea
  • Vomiting
  • Diarrhoea
  • Dry mouth
  • Small increased risk of suicidal thoughts and behaviour when initiating treatment

Contraindications

Cautions

  • Patients should be safety-netted on the signs and symptoms of myelosuppression and should seek immediate help should they arise. These may be:
    • Unexplained bruising
    • Unexplained bleeding
    • Sore throat
    • Fever
  • Patients should seek immediate help if they develop rashes, especially if they are severe with flushing, blisters, or ulcers – these can be signs of Stevens-Johnson syndrome

Monitoring

  • Lamotrigine levels themselves are not routinely monitored unless there is:
    • Evidence of ineffectiveness
    • Poor compliance
    • Toxicity is suspected

Phenytoin

Mechanism of action

Non-specific sodium ion channel blocker and targets nearly all voltage-gated sodium ion channels.

Adverse effects

  • Teratogenicity – associated with cleft palate and congenital heart disease
  • P450 inducer
  • Headaches
  • Drowsiness dizziness
  • Diplopia
  • Nystagmus
  • Slurred speech
  • Ataxia
  • Constipation
  • Sore/swollen gums
  • Stevens-Johnson syndrome
  • Toxic epidermal necrolysis
  • Myelosuppression – aplastic anaemia
  • Folate-deficiency anaemia
  • Peripheral neuropathy
  • Osteomalacia
  • Fever
  • Hepatitis
  • Coarse skin
  • Hirsutism

Contraindications

  • Acute porphyria

Cautions

  • Patients should be safety-netted on the signs and symptoms of myelosuppression and should seek immediate help should they arise. These may be:
  • Unexplained bruising
  • Unexplained bleeding
  • Sore throat
  • Fever
  • Patients should seek immediate help if they develop rashes, especially if they are severe with flushing, blisters, or ulcers – these can be signs of Stevens-Johnson syndrome

Monitoring

  • Phenytoin itself is not routinely monitored however trough levels (the levels just before another dose would be given) before giving a dose should be checked if:
    • The dose is being adjusted
    • There is suspected non-adherence
    • There is suspected toxicity

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