Depakote, which is manufactured by AbbVie (and formerly by Abbott Laboratories), comes in several dosage forms, including Depakote tablets, Depakote ER extended-release tablets, and Depakote Sprinkle Capsules (delayed release capsules). A closely related medication, Depakene (valproic acid), comes in capsule and liquid form. (Another variety of valproic acid, Stavzor, is no longer made.) In 2008, the U.S. Food and Drug Administration (FDA) approved the first generic version of Depakote. Collectively these drugs are known as valproate products.
Depakote is approved by the FDA to treat epilepsy, bipolar disorder and migraine headaches.
Depakote is used to treat epilepsy, a brain disorder that causes recurring, unprovoked seizures. Depakote blocks voltage-gated sodium channels in the brain and helps prevent brain signals that lead to seizures. Depakote may be prescribed either alone or in combination with other medications to treat epilepsy for adults and children 10 and older who suffer from complex partial seizures and simple and complex absence seizures. The FDA approved Depakote in 1983 for epilepsy treatment.
Depakote treats bipolar disorder manic episodes, which are marked by feelings of euphoria, elevated energy levels, and heightened creativity. During the manic phase of bipolar disorder people may have racing thoughts, talk rapidly, be highly distractible, and act recklessly. Depakote acts as a mood stabilizer. Depakote and other valproate medications work by increasing the amount of the neurotransmitter gamma-aminobutyric acid (GABA) in the brain, which contributes to motor control, vision, and other cortical functions. GABA also regulates anxiety. The U.S. Food and Drug Administration (FDA) approved Depakote in 1995 for bipolar disorder.
Depakote is also used to lessen the recurrence of migraine headaches. Although researchers have not pinpointed what causes migraines, many believe they are caused by a mix of genetic and environmental factors. Depakote is an effective prophylactic when taken before the onset of migraines. The U.S. Food and Drug Administration (FDA) approved Depakote in 1996 for the prevention of migraine headaches. Depakote has been approved for use in adults and children 10 and older for seizure treatment and age 16 and older for migraine prevention. It is not approved to treat bipolar conditions in children.
Depakote Indications and Precautions
For seizures, the recommended initial dose depends on the weight of the patient. For mania, the recommended initial dosage is 750 mg in divided doses. For migraine prevention, the typical initial dose of Depakote is 250 mg twice per day, but doses of up to 1500 mg per day are common.
Depakote manufacturer AbbVie warns that you should not take Depakote or Depakene if you:
- Have liver problems
- Have or think you have a genetic liver problem caused by a mitochondrial disorder (e.g. Alpers-Huttenlocher syndrome)
- Are allergic to divalproex sodium, valproic acid, sodium valproate, or any of the ingredients in Depakote or Depakene
- Have a genetic problem called urea cycle disorder
- Are pregnant
A common side effect of Depakote and Depakene is nausea, especially during the first month of treatment. This can be overcome by starting on a low dosage and slowly increasing the amount. Taking the medication on a full stomach can also help.
Rare side effects of Depakote and Depakene include:
- Liver problems
- Low platelets
- Pancreatitis (inflammation of the pancreas). Symptoms of pancreatitis include severe stomach pain, nausea, vomiting, and not feeling hungry.
- Increased ammonia levels. Symptoms may include confusion, disorientation, or difficulty thinking.
Serious side effects of Depakote and Depakene include:
- Liver and pancreas damage
- Birth defects
- Suicidal thoughts
Also, women who take Depakote are more likely to develop polycystic ovarian syndrome (PCOS), which can cause ovarian cysts and affect the ability to get pregnant. Depakote’s serious side effects, especially birth defects, have led to numerous lawsuits against the drug’s maker.
Depakote and Liver and Pancreas Damage
Depakote is labeled with an FDA warning that it can cause liver failure and pancreatitis in children and adults. Liver damage (hepatotoxicity) is especially common during the first six months of treatment. Doctors typically require blood tests to monitor liver function. People with an inherited disease that inhibits the body from converting food to energy, such as a urea cycle disorder, may risk developing liver damage if they take Depakote. Serious liver damage can cause death, especially in children younger than two. The risk of serious liver damage is higher within the first six months of treatment. Depakote is also linked to pancreatitis, a painful inflammation of the pancreas. Pancreatitis, although rare, can occur at the beginning of treatment with Depakote or after many years of use.
Depakote and Birth Defects
Studies have shown that Depakote can cause harm to human fetuses and should only be taken during pregnancy if no other medications can be used to treat a condition. Depakote can cause birth defects, including neural tube defects such as spina bifida, cleft palate and lowered intelligence. These defects occur in fewer than two out of every 100 babies born to mothers who use Depakote or Depakene during pregnancy. These defects can begin in the first month of pregnancy, even before a woman knows she is pregnant. Depakote may be responsible for other birth defects that affect the structures of the fetus’s heart, head, arms, legs and penis and can lower IQ. In addition, Depakote is excreted in breast milk; its effect on infants is unknown.
Neural Tube Defects, Including Spina Bifida
Depakote can cause neural tube defects, in which the brain, spine or spinal cord is damaged. In 2009 the FDA added a warning to Depakote concerning the danger of neural tube birth defects. The FDA found that taking Depakote during pregnancy increases the risk of developing birth defects such as neural tube defects from 1 in 1,500 babies to 1 in 20. A study published in the New England Journal of Medicine indicated that children whose mothers took Depakote during the first trimester of pregnancy are more than 12 times more likely to be born with spina bifida, a neural tube defect that results from the spinal column not completely closing during fetal development, leaving the spinal cord exposed.
Other Physical Defects
Researchers comparing other studies of valproic acid against the European Surveillance of Congenital Anomalies (EUROCAT) antiepileptic study database found six malformations linked to women’s Depakote use during the first trimester of pregnancy, including spina bifida and:
- Atrial septal defect (ASD), a hole in the wall between the two upper chambers (atria) of the heart
- Cleft palate, a condition where the tissue that makes up the roof off the mouth fails to join completely
- Hypospadias, a condition where the opening of the urethra in boys is on the underside of the penis rather than the end
- Craniosynostosis, a condition where the bones of the skull close too early
- Polydactyly, an extra finger or toe
The FDA warns that children born to mothers taking Depakote during pregnancy received lower scores on cognitive tests, such as IQ tests, than children born to mothers who take other anti-seizure medications. The tests were given at multiple ages and measured intelligence, abstract reasoning and problem-solving. An article published in the Journal of the American Medical Association linked prenatal valproate exposure to autism spectrum disorders and childhood autism.
Depakote and Suicide
A 2008 FDA analysis of 199 trials of people taking antiepileptic drugs, including Depakote, found that those taking the drugs have twice the risk of suicidal thinking than patients taking a placebo. The analysis revealed an increase in suicidal thinking and behavior in one in every 530 people treated. Suicidal thoughts and behavior were observed within seven days of treatment.
Psychiatrists warn that families and caregivers of anyone with bipolar disorder should be alert for warning signs:
- Thoughts about suicide or dying
- Attempts to commit suicide
- New or worsening depression
- New or worsening anxiety
- Feeling agitated or restless
- Panic attacks
- Trouble sleeping (insomnia)
- New or worsening irritability
- Acting aggressive, being angry or violent
- Acting on dangerous impulses
- An extreme increase in activity and talking (mania)
- Other unusual changes in behavior or mood