About Sodium Valproate

The most common brand name for sodium valproate in Australia is Epilim which is manufactured by Sanofi. Other manufacturers supply generic brands of valproate in Australia such as APO sodium valproate and Valpro. In other countries major brand names include Depakote, Depakene and Epival.

Valproate (also known as valproic acid, valproate semi sodium and divalproex sodium) belongs to the anticonvulsant or antiepileptic class of drugs. While it is an anticonvulsant that is very effective for managing epilepsy, it is also used as a mood stabiliser for bipolar disorder to manage mania. It has been in use in Australia since the 1960s (a) and subsidised by the PBS since 1978 (b).

Valproate has attracted much attention over the last decade as a result of extensive international research establishing solid evidence that it is a teratogenic drug. Consensus has been reached in the research and medical communities that the rate of major congenital malformation (physical birth abnormalities) is 11% when valproate is taken during pregnancy. It also causes neurodevelopmental delay/disability in 30-40% of exposed children. The harm caused by valproate has been demonstrated to be dose related with higher doses being associated with greater rates and degree of harm to the child.(c)

Due to the high risk with exceptionally poor health outcomes if a child is exposed to valproate during gestation, many countries around the world have implemented considerable restrictions to minimise the impact of the drug but enabling it to remain available to those for whom there is no risk of pregnancy as it remains one of the most effective drugs for both epilepsy and bipolar disorder. (d)

Where restrictions have been implemented, they are not limited to women who are pregnant. Due to the risk, it also includes all people of childbearing potential. This is important to ensure unintentional pregnancy is also accommodated.

Preliminary studies now that indicate an increased risk of an adverse congenital outcome if a male by birth is using valproate and conceives a child within a few weeks of taking the drug or while still using it.(e) To apply a cautious approach, the UK have introduced the same restrictions for all people of child conceiving age irrespective of sex at birth.(f)

As there are directives and policies that promote change of treatment for people using valproate, it is important for consumers to approach any change carefully with the guidance of a psychiatrist or neurologist. Due to its effectiveness, if valproate is ceased rapidly, there is high risk of the onset of seizures or mania for epilepsy and bipolar disorder respectively.(g) Both of these can be life-threatening conditions.

In Australia no significant restrictions have been introduced to reduce prescribing of valproate despite it being known that doctors do not provide adequate information to patients when prescribing.(h) Very little consumer information is available and it is difficult to find.

In October 2024, the Royal Australian & New Zealand College of Psychiatrists published on their website an endorsement of the 2018 UK Royal College of Psychiatrists (RANZCP) position statement on valproate. The RANZCP recommends that “sodium valproate should not be prescribed to women and girls of child-bearing age, or without a Long Acting Reversible Contraceptive (LARC) agent. Women and girls should also be required to sign a form acknowledging their understanding of the risks of taking sodium valproate.” These are recommendations for clinical practice and are not mandated.(i) The endorsement is consistent with the recommendations made by the Advisory Committee on Medicines in April 2024 when the regulation of valproate was reviewed at the request of the TGA.(j)

In order to reduce prescribing of valproate to people of childbearing potential with epilepsy, the PBS subsidy conditions for lamotrigine and levetiracetam which are both non-teratogenic anticonvulsants were changed to remove the barrier of affordability to less harmful medicines.(k) No similar interventions have been undertaken to reduce prescribing to people of childbearing potential with bipolar disorder.

(a) https://www.tga.gov.au/resources/publication/meeting-statements/acm-meeting-statement-meeting-9-31-may-1-june-2018 accessed 2/12/2024

(b) https://www.pbs.gov.au/publication/schedule/1951-2002/1978-12-01-consolidated-schedules.pdf accessed 2/12/2024

(c) https://assets.publishing.service.gov.uk/media/65660310312f400013e5d508/Valproate-report-review-and-expert-advice.pdf accessed 2/12/2024

(d) https://www.ema.europa.eu/en/medicines/human/referrals/valproate-related-substances-0 accessed 2/12/2024

(e) https://www.ema.europa.eu/en/news/precautionary-measures-address-potential-risk-neurodevelopmental-disorders-children-born-men-treated-valproate-medicines accessed 2/12/2024

(f) https://assets.publishing.service.gov.uk/media/66d99722293afcbf8a811102/Advice_for_male_patients_on_valproate_to_use_contraception_PUBLISH_.pdf accessed 2/12/2024

(g) https://www.nhs.uk/medicines/sodium-valproate/ accessed 2/12/2024

(h) https://journals.sagepub.com/doi/full/10.1177/10398562231197286 accessed 2/12/2024

(i) https://www.ranzcp.org/clinical-guidelines-publications/clinical-guidelines-publications-library/valproate-in-healthcare accessed 1/12/2024

(j) https://www.tga.gov.au/sites/default/files/2024-11/FOI%205351.pdf 2/12/2024

(k) https://m.pbs.gov.au/industry/listing/elements/pbac-meetings/pbac-outcomes/2020-09/other-matters-09-2020.pdf accessed 2/12/2024