SODIUM VALPROATE

This section is designed to inform professionals.

(Consumers, see Fact Sheet on Sodium Valproate)

Available as Epilim.

Sodium Valproate (Valproic acid) is an anticonvulsant which is also an effective mood stabiliser and used in the treatment of Bipolar Affective Disorder.

It is effective as an anti-manic medication and in prophylaxis of recurrent episodes in Bipolar Disorder.

Use in Pregnancy

Category D

Sodium Valproate use in pregnancy is associated with the development of a range of major abnormalities, including facial dysmorphias (characterized by mid-face hypoplasia, short nose with anteverted nostrils, and long upper lip), distal digit hypoplasia, and neural tube defects.
Much of the data comes from the use of these drugs in the treatment of epilepsy.
Studies show that the use of Sodium Valproate in pregnancy (particularly in the first trimester) is associated with an increase in birth abnormalities, particularly when used in combination with other anti- epileptic drugs (especially carbamazepine and Lamotrigine)
The risk is increased substantially, one study suggesting as much as 30% (4) when doses of more than 1 gram/day of Sodium Valproate were used.
Valproate use in early pregnancy increases the rate of neural tube defects significantly. The rate of neural tube defects in the general population has been estimated at 0.06%, Valproate increases the rate to between 1% and 2% (and even higher when used in combination with other anti–epileptic drugs, or if the dose is over 1,000mg).
There is emerging evidence that that the use of sodium valproate may be associated with a significant reduction in the cognitive functioning of children born to women who used valproate throughout pregnancy.
Sodium Valproate has also been associated with intrauterine growth retardation, hyperbilirubinemia, hepatotoxicity, skeletal dysplasia, and foetal/newborn distress.
There is evidence that folic acid supplements can reduce the general population’s incidence of neural tube defects and women planning pregnancy are advised to take 0.4 mg of folic acid per day before conception and during the first 12 weeks of pregnancy.
Given the association of sodium valproate with neural tube defects, and the fact that it interferes with folic acid metabolism, it is recommended that women of child-bearing potential who are taking sodium valproate, should take folic acid supplements. Women taking sodium valproate should take 5mg folic acid daily. However, to date, no study has demonstrated that prescribing folic acid supplements to women taking anticonvulsants during pregnancy reduces the risk of neural tube defects. It is important that taking folic acid does not imply that discussion and decisions regarding the balancing of the benefits and risks are no longer necessary.
Sodium Valproate can also cause neonatal complications which include heart rate decelerations and withdrawal symptoms of irritability, jitteriness, feeding difficulties, and abnormal tone. Other complications among neonates include liver toxicity and hypoglycemia.

Use in Lactation

Category L2

Studies have shown that the amount of sodium valproate transferring to the infant in breast milk is low. The amount has been calculated to be less than about 1% of the maternal levels.
It is however recommended that the infant’s liver functions and platelets are monitored.
There are some anecdotal reports that it exposure via the breast milk may cause some developmental delay.

Conclusions

If a woman who is taking Valproate is planning a pregnancy, or is pregnant, careful consideration should be given to stopping the medication.
The risks of continuing it are considerable but the risks of her bipolar disorder may be greater.
Where appropriate in the treatment of bipolar disorder, an alternative drug should be considered.
If there is no alternative to Valproate, doses should be limited to a maximum of 1 gram per day, administered in divided doses and in the slow release form, with 5 mg/day folic acid.

References

(1) Chaudron, L., & Jefferson, J. (2000). Mood Stabilisers During breast Feeding: A Review. Journal of Clinical Psychiatry, 61(2): 79-90.

(2) Dean, J., Hailey, H., Moore, S., Lloyd, D., Turnpenny, P., Little, J. (2002) Longterm health and neurodevelopment in children exposed to antiepileptic drugs before birth. Journal of medical Genetics, 39:251-259.

(3) Delgado-Escueta AV. (1992). Consensus guidelines: Preconception counselling, management, and care of the pregnant woman with epilepsy; Neurology, 42: 5, 149-160

(4) Vajda, F., O’Brien, T., Hitchcock, A., Graham, J., Cook, M., Lander, C., Eadie, M. (2004). Critical relationship between sodium valproate dose and human teratogenicity: results of the Australian register of anti-epileptic drugs in pregnancy. Journal of Clinical Neuroscience; 11(8): 854-858.