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Depakote: 7 things you should know

Medically reviewed by Carmen Fookes, BPharm. Last updated on Jun 9, 2020.

1. How it works

  • Depakote is a brand (trade) name for divalproex sodium. Depakote may be used to treat certain types of seizure disorder, to reduce mania in people with bipolar disorder, and as a preventive treatment for migraines.
  • Experts are not exactly sure how Depakote works although they suspect its activity is related to increased brain concentrations of gamma-aminobutyric acid (GABA) - a neurotransmitter in the brain that calms nervous activity.
  • Depakote belongs to the class of medicines known as antiepileptics (AEDs) or anticonvulsants.

2. Upsides

  • May be used either alone or in combination with other antiepileptics for the treatment of complex partial seizures, absence seizures, and for several other types of seizure.
  • May be used to control manic episodes in people with bipolar disorder.
  • May be effective for the prevention of migraine headaches in some people.
  • Depakote is available as a generic under the name divalproex (may also be called divalproex sodium).

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

  • Abdominal pain, nausea, diarrhea, constipation, dizziness, drowsiness, weakness, or weight loss. May also cause bleeding gums, bloating or swelling, cough, a tremor, hair loss, ataxia, nystagmus, a skin rash, and thinking difficulties.
  • Side effects such as an increase in liver enzymes and thrombocytopenia (a decrease in platelet numbers in the blood) are more prevalent at higher dosages.
  • Depakote may not be suitable for everyone including those with depression or other mental illness, HIV or cytomegalovirus infection, liver disease, mitochondrial disorders, or urea cycle disorders. Elderly people may be more sensitive to side effects including drowsiness.
  • Depakote should be used with caution in women with child-bearing potential. Contraceptives should always be taken alongside Depakote and you should talk with your doctor before attempting to conceive, because Depakote has been associated with birth deformities.
  • May cause fatal liver failure; the risk is greatest in children aged less than two and people with underlying conditions (such as a mitochondrial disorder, preexisting liver disease, or a urea cycle disorder).
  • Depakote is not recommended for migraine prophylaxis in pregnant women. If you are using Depakote to treat epilepsy of manic episodes use effective birth control and speak to your doctor before choosing to become pregnant. Depakote can cause birth defects in unborn children.
  • Cases of life-threatening pancreatitis have been reported in both children and adults receiving valproate short-term or long-term; symptoms include abdominal pain, nausea, vomiting, and weight loss.
  • As with other antiepileptics, Depakote may increase the risk of suicidal thoughts or behavior particularly in young adults under the age of 24. Monitor for worsening mood.
  • May interact with a number of different medicines including aspirin, other antiepileptics, carbapenem antibiotics, felbamate, and rifampin.

Notes: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. For a complete list of all side effects, click here.

4. Bottom Line

Depakote may be used in the treatment of epilepsy, mania, and to prevent migraines; however, people taking Depakote should be monitored for potentially fatal side effects such as liver failure and pancreatitis and it should not be used in women of childbearing age unless benefits outweigh risks and reliable contraception is used.

5. Tips

  • Swallow Depakote tablets whole, do not crush or chew. Depakote sprinkle capsules may be opened and the medicine sprinkled onto a spoonful of pudding or applesauce to make swallowing easier.
  • Dosage depends on a number of patient factors including age, medical condition for which Depakote is prescribed, sensitivity to side effects, the presence of dehydration and nutritional status.
  • Always take Depakote with plenty of water and maintain good hydration throughout the day.
  • If you experience stomach upset while taking Depakote, try taking with food or ask your doctor if you can titrate your dosage more slowly.
  • May cause drowsiness and affect your ability to drive or operate machinery. Avoid alcohol
  • Be alert for changes in behavior including agitation, depressed mood, and suicide-related events and seek medical advice if changes are apparent.
  • Always take Depakote exactly as prescribed. Never take too much Depakote or stop suddenly without your doctor's advice. Symptoms of overdosage of Depakote include changes in consciousness, fainting, and slow or irregular heartbeat.
  • If you are a woman with child-bearing potential, always use adequate contraception and talk to your doctor about alternative treatments before you conceive, because Depakote may cause birth defects.
  • Contact your doctor urgently if you experience stomach pain that spreads to your back, nausea and vomiting, dark urine, facial swelling, loss of appetite, or yellowing of the skin or eyes. Also contact your doctor if you experience any mood changes, unusual bruising or bleeding, flu-like symptoms, severe skin reactions, or worsening of your symptoms.
  • Blood tests may be needed to monitor the effects of Depakote.
  • Always tell your dentist or healthcare provider that you take Depakote. Wearing a medical alert tag is a good idea.
  • Avoid excessive sunlight exposure or tanning beds as Depakote may make you burn more easily. Wear sunblock and protective clothing when outdoors.

6. Response and Effectiveness

  • The time it takes for Depakote to reach its peak effects depends on the formulation used. Tablets take 4 hours to reach a peak, Depakote sprinkles take just over three. Food can delay the absorption of Depakote (food has a more significant effect on the tablets compared with the sprinkles).
  • It may take several weeks of regular dosing before an effect on mood or seizure frequency is reported.

7. Interactions

Medicines that interact with Depakote may either decrease its effect, affect how long it works for, increase side effects, or have less of an effect when taken with Depakote. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with Depakote include:

  • antibiotics such as clarithromycin, doxycycline, erythromycin
  • anticonvulsants such as lamotrigine, phenytoin, and phenobarbitone
  • antidepressants, such as desipramine, doxepin, isocarboxazid, nefazodone, phenelzine or venlafaxine
  • antihistamines, such as azelastine, cetirizine, or levocetirizine
  • antipsychotics, such as aripiprazole, clozapine, haloperidol, or quetiapine
  • aspirin
  • carbapenem antibiotics, such as ertapenem, imipenem, or meropenem
  • clonidine
  • dextromethorphan
  • felbamate
  • folic acid
  • HIV medications such as indinavir and ritonavir
  • estrogen or progestin-containing oral contraceptives and hormonal treatments
  • medications that cause drowsiness, such as benzodiazepines, sedating antihistamines, and sleeping pills
  • methotrexate
  • metoclopramide
  • montelukast
  • muscle relaxants, such as baclofen
  • opioid analgesics such as buprenorphine, codeine, fentanyl, oxycodone, and morphine
  • rifampin
  • tramadol
  • trazodone.

Alcohol may worsen the side effects of Depakote such as drowsiness, dizziness, and liver toxicity.

Note that this list is not all-inclusive and includes only common medications that may interact with Depakote. You should refer to the prescribing information for Depakote for a complete list of interactions.


Depakote (divalproex sodium delayed-release tablets) [Package Insert] Revised 12/2019.

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Depakote only for the indication prescribed.

Copyright 1996-2020 Revision date: June 9, 2020.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.