Most side effects from taking valproic acid go away with no lasting harm. But a few people have serious reactions that can even be life-threatening.

Here's a list of symptoms that may be the start of one of these problems. If you notice any of these symptoms, call the doctor immediately:

• weakness, sluggishness, swelling of the face, loss of appetite, vomiting, or yellowing of the skin and eyes, especially in a child under 2 years of age (possible liver failure)
• pain in the abdomen, upset stomach, vomiting, or loss of appetite (possible disease of the pancreas)
• easy bruising, nosebleed, other abnormal bleeding (problems with clotting)

The best-known and most feared serious reaction is liver damage, which has been fatal for some people. This damage usually occurs within the first 6 months of treatment. The risk of liver failure is much higher in children under 2 years of age, especially if they:

• also take other seizure medicine
• have a severe seizure disorder with mental retardation
• have another brain disease, or
• have an inborn disorder of metabolism

The risk of liver failure is much lower in children between 2 and 10 and is very low in older children and adults, perhaps 1 in 50,000. This is similar to the frequency of liver failure when taking other seizure medicines, such as Dilantin (phenytoin). There is no evidence that long-term use of valproic acid will cause gradual, progressive damage to the liver.

Another rare but potentially life-threatening reaction to valproic acid is pancreatitis (inflammation of the pancreas), which occasionally progresses to bleeding and death. This reaction may occur in both children and adults, even after several years of taking valproic acid. Report pain in the abdomen, upset stomach, vomiting, or loss of appetite to the doctor right away.

Problems with blood clotting are more likely when high doses of valproic acid are taken. Sometimes these problems return to normal without stopping the valproic acid. The doctor probably will order some blood tests before starting treatment with valproic acid, and will repeat them some time later and before any elective surgery.

A complete list of all reactions to valproic acid can be found in the package insert for the brand-name version, Depakene, but it is important to remember that only a tiny number of people have any of these serious problems.

On July 10, 2008, an advisory panel was convened by the Food and Drug Administration (FDA) to review data that the FDA had previously collected from drug studies showing an association between many of the antiepileptic drugs (AEDs) and suicidal ideation and behavior, which together are called suicidality. According to the FDA’s Alert, among the patients with epilepsy in these drug studies, 1 out of 1000 people taking the placebo (inactive substance) showed suicidality compared to approximately 3.5 out of 1000 people who took an AED. The FDA advisory panel voted to accept the FDA's data at its meeting on July 10. The FDA has provided the following information for patients, family members, and caregivers at www.fda.gov/cder/drug/InfoSheets/HCP/antiepilepticsHCP.htm.

• Taking antiepileptic medicines may increase the risk of having suicidal thoughts or actions;
• Do not make any changes to the medication regimen without first talking with the responsible healthcare professional;
• Pay close attention to any day-to-day changes in mood, behavior and actions. These changes can happen very quickly so it is important to be mindful of any sudden differences.
• Be aware of common warning signs that might be a signal for risk of suicide. Some of these are:
  • Talking or thinking about wanting to hurt yourself or end your life
  • Withdrawing from friends and family
  • Becoming depressed or having your depression get worse
  • Becoming preoccupied with death and dying
  • Giving away prized possessions

We again urge patients and families to contact their doctor before stopping an epilepsy medication because this may possibly lead to seizures and worsening of mood.

Reviewed July 2008 by Steven C. Schachter, MD, epilepsy.com Editorial Board.