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
- May exacerbate myoclonic seizures
- May exacerbate Parkinson’s disease
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