Sodium valproate inhibits the breakdown and reuptake of the inhibitory neurotransmitter gamma aminobutyric acid (GABA).
This agent is useful in the primary generalised epilepsies, particularly petit mal. It is also useful in generalised tonic-clonic attacks, particularly those patients with a photosensitive EEG.
Sodium valproate is also useful in myoclonic epilepsy. It does not interfere with the oestrogen component of the contraceptive pill, unlike carbamazepine and the barbiturates.
Valproate is a possible treatment option for long term management in bipolar disorder*
NICE (1) suggest with respect to:
- when starting valproate, measure the person's weight or BMI and carry out a full blood count and liver function tests
- people taking valproate, and their carers, should be advised how to recognise the signs and symptoms of blood and liver disorders and to seek immediate medical help if any of these develop. Stop valproate immediately if abnormal liver function** or blood dyscrasia is detected
- prescribers should be aware of its interactions with other anticonvulsants (particularly carbamazepine and lamotrigine) and with olanzapine and smoking
In 2018, a large-scale review of the safety of valproate led to regulatory changes intended to reduce the number of unborn babies exposed to valproate. These included a ban on the use of valproate for migraine or bipolar disorder during pregnancy, and a ban on the use of valproate to treat epilepsy during pregnancy unless no other effective treatment is available (2)
- exposure to valproate in pregnancy is associated with physical birth defects in 11% of babies and neurodevelopmental disorders in up to 30-40% of children, which may lead to permanent disability
The UK’s medicines regulator the Medicines and Healthcare products Regulatory Agency (MHRA) requires that valproate must not be used in any woman or girl able to have children unless there is a pregnancy prevention programme (PPP) in place (2).
Advice for healthcare professionals:
- valproate must not be started in new patients (male or female) younger than 55 years, unless two specialists independently consider and document that there is no other effective or tolerated treatment, or there are compelling reasons that the reproductive risks do not apply. For the majority of patients, other effective treatment options are available
- at their next annual specialist review, women of childbearing potential and girls receiving valproate should be reviewed using the revised valproate Annual Risk Acknowledgement Form. A second specialist signature will be needed if the patient is to continue on valproate, however subsequent annual reviews will only require one specialist
- general practice and pharmacy teams should continue to prescribe and dispense valproate and if required offer patients a referral to a specialist to discuss their treatment options. Valproate should be dispensed in the manufacturer’s original full pack
- report suspected adverse drug reactions associated with valproate on a Yellow Card
The summary of product characteristics should be consulted before prescribing this drug.
Notes:
- valproate treatment must not be used in girls and women including in young girls below the age of puberty, unless alternative treatments are not suitable and unless the conditions of the pregnancy prevention programme are met
- since 2018, valproate has been contraindicated in women of childbearing potential unless the conditions of the Pregnancy Prevention Programme (PPP) are followed (2)
- with respect to stopping valproate in bipolar disorder (1):
- if stopping valproate, reduce the dose gradually over at least 4 weeks to minimise the risk of relapse
Reference:
- NICE (April 2018). Bipolar disorder
- MHRA . Valproate (Belvo, Convulex, Depakote, Dyzantil, Epilim, Epilim Chrono or Chronosphere, Episenta, Epival, and Syonell▼): new safety and educational materials to support regulatory measures in men and women under 55 years of age.Drug Safety Update volume 17, issue 6: January 2024: 1