Valproic acid is a chemical compound that has found clinical use as an anticonvulsant and mood-stabilizing drug, primarily in the treatment of epilepsy and bipolar disorder; but also used to treat migraine headaches and schizophrenia. In epileptics, valproic acid is used to control absence seizures, tonic-clonic seizures (grand mal), complex partial seizures, and the seizures associated with Lennox-Gastaut syndrome.

Related drugs include the sodium salts sodium valproate, used as an anticonvulsant, and a combined formulation, valproate semisodium, used as a mood stabilizer and additionally in US also as an anticonvulsant.

Valproate is believed to affect the function of the neurotransmitter GABA (as a GABA transaminase inhibitor) in the human brain, making it an alternative to lithium salts in treatment of bipolar disorder.

Valproic acid is an inhibitor of the enzyme called histone deacetylase 1 (HDAC1). HDAC1 is needed for HIV to remain in infected cells. A study published in August 2005 revealed that patients treated with valproic acid in addition to highly active antiretroviral therapy (HAART) showed a 75% reduction in latent HIV infection. This may one day lead to a cure for HIV and AIDS.

Another potential indication may be leukemia in juvenile patients. Studies conducted by several European centres are ongoing. Although it is too early to make a definitive statement, preliminary results are encouraging.

Side effects

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Common side effects are dyspepsia and/or weight gain. Less common are dizziness, drowsiness, hair loss, headaches, nausea, sedation and tremors.

Rarely, valproic acid can cause blood dyscrasia, impaired liver function, jaundice, thrombocytopenia, and prolonged coagulation times. In about 5% of pregnant users, valproic acid will cross the placenta and cause congenital anomalies. Due to these side effects, most doctors will ask for blood tests, initially as often as once a week and then once every 2 months. Temporary liver enzyme increase has been reported in 20% of cases during the first few months of taking the drug. Inflammation of the liver (hepatitis), the first symptom of which is jaundice, is found in rare cases.

There have also been rare reports of cognitive dysfunction, Parkinson's disease, and even pseudoatrophic brain changes in long-term treatment with valproic acid.

Contraindications

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Valproate is contraindicated in overweight patients because it causes weight gain as outlined above, and in pregnant women because it is teratogenic. Preexisting liver damage, bone marrow depression, and coagulation disorders are additional contraindications. It is relatively contraindicated in pregnancy due to its teratogenicity; women who become pregnant whilst taking valproate should be counselled as to its risks, take high dose folic acid and be offered antenatal screening (alpha-fetoprotein and second trimester ultrasound scans).British National Formulary (March 2003) 45

Formulations

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Branded products include Depakene® (Abbott Laboratories in US & Canada), Convulex® (Pfizer in UK and Byk Madaus in South Africa).

References

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External links

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• The Lundbeck Institute Guide to Psychotropics - Valproic acid
• http://www.psycheducation.org/depression/meds/moodstabilizers.htm
• http://www.psycheducation.org/depression/meds/valproate.htm
• Crazy Meds: Depakene
• The Comparative Toxicogenomics Database:Valproic Acid
• Chemical Land21: Valproic Acid
• RXList.com: Depakene (Valproic Acid) (US)
• South African Electronic Package Inserts: Convulex
• Med Broadcast.com: Valproic Acid (Canadian)

Anticonvulsants | Mood stabilizers | Teratogens | Carboxylic acids

Valproinsäure | Acide valproïque | Valproato | Вальпроевая кислота | Valproinsyra