Introduction

Depakote is a brand name drug manufactured by AbbVie and approved by the U.S. Food and Drug Administration (FDA) to treat epilepsy and bipolar disorder. It is also FDA-approved for prevention of migraines. The drug is also manufactured by several other companies and sold under the generic name divalproex sodium. The chemical structure of Depakote is similar to the brand name Depakene (valproic acid). While the two have similar uses, they are not interchangeable and come in different dosage forms.

Depakote belongs to a class of medications called antiepileptic drugs (AEDs), also known as anticonvulsants. Many drugs in this class are not completely understood, but conventional AEDs likely work by blocking sodium channels in nerve cells and enhancing the activity of a neurotransmitter called gamma-aminobutyric acid (GABA). Together, these interventions prevent repetitive firing of nerve signals in the brain. Preventing abnormal activity in the brain can reduce mood disorder symptoms and prevent seizures and migraines.

Depakote forms and strengths

Depakote is available in three oral formulations: delayed-release tablets, extended-release tablets (Depakote ER), and delayed-release sprinkle capsules (Depakote Sprinkle Capsules). Depakote ER allows for once-daily dosing, and sprinkle capsules allow Depakote to be mixed into soft food such as applesauce, yogurt, pudding, oatmeal, or ice cream.

• [Delated-release tablets]: 125 mg, 250 mg, and 500 mg
• [Extended-release tablets]: 250 mg and 500 mg
• [Delayed-release sprinkle capsules]: 125 mg

Depakote dosage for adults

Depakote dosage chart

Indication

Starting dosage

Standard dosage

Maximum dosage

Acute manic bipolar disorder

250 mg three times daily.

Extended-release: 25 mg/kg per day as a single dose

500 mg three times daily.

Extended-release: 2000 mg once daily.

60 mg/kg daily, no single dose should exceed 250 mg

Complex partial seizures

10-15 mg/kg daily, divided into one to three doses. Increase by 5-10 mg/kg/day every seven days.

30-60 mg/kg daily, divided into two or three doses.

Extended-release: 30-60 mg/kg daily as a single dose

60 mg/kg daily, no single dose should exceed 250 mg

Simple and complex absence seizures

15 mg/kg daily, divided into one to three doses. Increase by 5-10 mg/kg/day every seven days.

30-60 mg/kg daily, divided into two or three doses.

Extended-release: 30-60 mg/kg daily as a single dose

60 mg/kg daily, no single dose should exceed 250 mg

Migraine prevention

250 mg twice daily

500 mg twice daily

1500 mg daily

Depakote dosage for acute manic bipolar disorder

Depakote is a first line therapy for patients diagnosed with bipolar disorder. It may be used alone (monotherapy) or in combination with other medications such as aripiprazole for the treatment of acute mania. Combination therapy may be more effective and provide faster benefits when compared with monotherapy. Doctors will prescribe an initial dose of 500 – 750 mg per day (or 25 mg/kg daily) and increase the dose by thirty to fifty percent every three days as tolerated. Maintenance dosages are usually in the range of 1,000 – 3,000 mg daily, to maintain. Depakote blood levels between 50-125 mcg/mL. Depakote blood levels are typically monitored every one to two weeks during the first two months of therapy, then every three to six months.

Depakote dosage for epilepsy

Depakote may be prescribed for absence seizures (which affect both sides of the brain) or partial seizures (which affect just one area of the brain). Absence seizures involve a sudden and brief lapse of consciousness, manifested as rapid blinking or a momentary blank expression. Partial seizures may involve muscle contractions, muscle weakness, unusual heady or eye movements, abdominal pain, increased heart rate, dilated pupils, changes in vision, hallucinations, numbness, or tingling. Partial seizures can be further categorized as simple or complex. During a simple partial seizure, the patient does not lose consciousness. During a complex partial seizure, the patient loses consciousness and does not remember what happened. Doctors typically start patients with epilepsy on 10-15 mg/kg or 250-750 mg of Depakote per day. The dose is increased by 5-10 mg/kg or 250-500 mg daily each week until seizures stop. Doctors will adjust the dose to minimize side effects and to maintain levels of Depakote in the blood between 50-1000 mcg/mL.

Depakote dosage for migraine headache prevention

Depakote is a first line agent for the prevention of migraines. According to an analysis of ten different studies, 1 out of 5 patients 16 years and older experienced a 50% reduction in migraine frequency when taking Depakote. The starting dose for migraine prevention is 250 mg twice daily. If that is not effective, the dose may be increased to 1500 mg daily in divided doses. Blood levels of the Depakote do not usually need to be monitored, although they may be useful for patients on the higher end of the dosage range to reduce risks of toxic side effects.

Depakote dosage for children

• Standard Depakote dosage for children ages 10 and above: 30-60 mg/kg daily, divided into two or three doses.
• Maximum Depakote dosage for children ages 10 and above: Total daily doses should not exceed 60 mg/kg daily. Any single dose should not exceed 250 mg.

Depakote dosage for children

Indication

Recommended dosage 

Complex partial seizures

Extended-release tablets: Start with 10-15 mg/kg divided into one to three doses daily, increasing by 5-10 mg/kg/day every seven days. The maximum dose is 60 mg/kg daily. Any single dose should not exceed 250 mg.

Simple and complex absence seizures

Delayed-release sprinkle capsules: Start with 15 mg/kg divided into one to three doses daily, increasing by 5-10 mg/kg/day every seven days. The maximum dose is 60 mg/kg daily. Any single dose should not exceed 250 mg.

Depakote dosage restrictions

Depakote should not be used in patients with POLG-related mitochondrial disorders (e.g., Alpers Huttenlocher Syndrome) due to an increased risk of liver failure and death when taking Depakote.

Patients diagnosed with pancreatitis should discontinue Depakote and start an alternative treatment. Life-threatening pancreatitis has occurred in adults and children shortly after starting Depakote therapy or several years into therapy. Signs and symptoms of pancreatitis include abdominal pain (stomach pain that radiates to your back), nausea, vomiting, and anorexia.

Adults and children with liver disease should avoid using Depakote if other treatment options are available. Patients younger than two years may experience fatal liver toxicity (hepatotoxicity) when using Depakote, especially when used with other seizure medications. If no alternative treatment options are available, use Depakote with extreme caution and as monotherapy in this age group.

Elderly patients are more predisposed to Depakote’s side effects such as tremors or drowsiness. Depakote should be started at a low dose in elderly patients compared to younger adults, and doses should be increased gradually to achieve effective treatment.

How to take Depakote

• Sprinkle capsule: You may open the capsule and pour the medicine onto a teaspoonful of soft food (including pudding or applesauce). Stir this mixture well and swallow it without chewing.
• Part of the medicine may pass into your stool after your body has absorbed the medicine. Check with your doctor right away if this happens.
• This medicine should come with a Medication Guide. Ask your pharmacist for a copy if you do not have one.
• Missed dose: Take a dose as soon as you remember. If it is almost time for your next dose, wait until then and take a regular dose. Do not take extra medicine to make up for a missed dose. If you miss 2 or more doses, call your doctor.
• Take your medicine as directed. Your dose may need to be changed several times to find what works best for you.
• You may take this medicine with food to decrease stomach upset.
• Capsule, tablet, or extended-release tablet: Swallow the medicine whole. Do not crush, break, or chew it.
• Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light.

Depakote dosage FAQs

How long does it take Depakote to work?

Depakote tablets reach peak levels in four hours, while the sprinkle capsules reach peak levels in three hours. Food can delay the absorption of Depakote, especially the tablets (absorption of tablets can take up to eight hours when taken with food). The time to absorption may differ depending on the administration method, for example whether the contents of the capsule are sprinkled on food, or the capsule is swallowed whole. However, the administration method will not impact the effectiveness of Depakote. The effects of Depakote are experienced after a period of regular use. For Depakote to have its effects, it must reach a stable concentration, called “steady state.” This condition is usually achieved in two to five days, depending on the patient’s age and weight. Once steady state is achieved, doctors can begin to assess how well Depakote is working and decide if a dose adjustment is needed. When starting Depakote, multiple dosage adjustments over a few weeks may be necessary before a patient notices an improvement in symptoms.

How long does Depakote stay in your system?

Healthcare professionals measure the time it takes to eliminate a drug from the body using a metric called a half-life; this is the time it takes the body to get rid of half the amount of drug currently in your system.

The half-life of Depakote depends on several factors such as a patient’s age, kidney, and liver function, how often Depakote is taken, and other medications that may interact with Depakote. When taken by itself, the half-life of Depakote is roughly fourteen hours, and it takes five half-lives to eliminate most drugs. So, while the levels of Depakote may not be high enough have clinical effects, Depakote can remain in your system for about three days following a single dose. 

Certain medications decrease the times it takes to clear Depakote from the body. For example, other seizure medications like carbamazepine, phenytoin, and phenobarbital can double the rate that Depakote is cleared. One study determined that taking 600 mg of rifampin daily increased the clearance rate of Depakote by 40%.

What happens if I miss a dose of Depakote?

If you miss a dose of Depakote, take the missed dose as soon as you can. However, you should skip the missed dose if it is almost time for your next dose. If you take Depakote once daily, and it is less than twelve hours until your next dose, skip the missed dose and take the next dose at the usual time. If you take Depakote two or three times daily, and it is less than two hours before the next dose is due, skip the missed dose and take your next dose at the usual time. Do not take two doses at one time. Missing doses of Depakote can increase your risk for recurrence of seizures or manic episodes, and the risk increases with each consecutive missed dose. It is best to take Depakote at the same time each day to help you remember each dose. Always remember to get your prescription refilled before you run out of medicine completely.

How long can you take Depakote?

Depakote is intended for long-term use. Patients with epilepsy need to be seizure-free for at least a few years before a doctor will consider stopping seizure medications. Many factors are considered when assessing whether it is safe to stop seizure medication, such as age of diagnosis, type and number of seizures experienced, etc. Many patients with epilepsy need treatment for life. Likewise, patients taking Depakote for bipolar disorder may require lifelong treatment. Long-term Depakote treatment increases risk for osteoporosis, blood clots, and liver damage. However, for many patients, the benefits of Depakote greatly outweigh these risks.

How do I stop taking Depakote?

Do not stop taking Depakote without asking your doctor. Abruptly stopping Depakote can result in withdrawal seizures and relapses in mood disorder symptoms. If a doctor decides to discontinue Depakote, the dose must be gradually decreased (tapered) before it is stopped completely. The length of the tapering period depends on the medical condition being treated, use of monotherapy vs. multiple medications to manage the condition, and patient-specific risk factors for relapse. In adults, Depakote is often decreased over six months, and in children the range is between six weeks and nine months.

Can you overdose on Depakote?

Taking too much Depakote can result in central nervous system dysfunction, liver toxicity, and pancreatitis. Symptoms can include vomiting, diarrhea, tremors, agitation, confusion, altered mental status, and seizures. Liver problems may not be evident upon examination but will manifest as elevated liver enzymes on a blood test. Acute overdoses can cause a brain condition called encephalopathy which may result in coma and death. Call poison control at 1 (800) 222-1222 if you suspect a Depakote overdose.

What interacts with Depakote?

Other antiepileptic drugs such as carbamazepine, phenytoin, and phenobarbital can lower the levels of Depakote, and may require increased dosages of Depakote to avoid relapses in mood symptoms or seizures.

A class of drugs called salicylates (aspirin, magnesium salicylate, etc.) can increase levels of Depakote by preventing a protein called albumin from binding up the active form of Depakote in the body.

A combination of Depakote and topiramate can lead to elevated ammonia levels (hyperammonemia) in the blood. This condition can result in lethargy, vomiting, and mental changes such as confusion. In more severe cases, it may lead to coma and vital sign changes. Additionally, taking the two drugs together can lower the efficacy of both drugs, resulting in loss of seizure control.

Certain medications such as estrogen-containing birth control and a class of antibiotics called carbapenems (imipenem, meropenem, etc.) can lower levels of Depakote. Monitor blood levels closely when starting or stopping an estrogen-containing product.

Depakote can increase the levels of certain medications that require careful dose adjustments, such as phenytoin and warfarin.

Extra caution must be exercised when combining Depakote with lamotrigine due to the increased risk of a serious rash called Stevens-Johnsons Syndrome (SJS). Use a lower starting dose of lamotrigine and increase the lamotrigine dose slowly.

Finally, patients with epilepsy should avoid certain medications that lower the seizure threshold such as bupropion, metoclopramide, and amifampridine. This is not an exhaustive list of all Depakote drug interactions. It is best to consult with a healthcare provider about potential interactions with other medications you are taking.

What happens when you mix Depakote and alcohol?

Taking Depakote for epilepsy or bipolar disorder does not necessarily mean you can’t take alcohol. However, it is very important to be aware of the risks of combining alcohol with Depakote. Alcohol can worsen some adverse effects of Depakote, including dizziness, drowsiness, and lowered concentration. It can also increase the chances of having a seizure, even in patients without epilepsy. For example, patients who drink excessively can experience ‘withdrawal seizures’ within seventy-two hours of abstaining from alcohol. Furthermore, alcohol’s effect on mood and judgment can hinder efforts to take medication properly. This is particularly dangerous for patients taking Depakote due to the risks of seizure or mood disorder relapse. Combining alcohol and Depakote can also increase impulsive behavior, suicide, injury, and hospitalization in patients with bipolar disorder. In general, it is best to limit or avoid alcohol while taking Depakote.

Is it safe to take Depakote during pregnancy?

Taking Depakote during pregnancy increases the risk for birth defects such as congenital neural tube defects (spina bifida), and congenital malformations of the heart, limbs, and genitals. It may also result in decreased IQ scores and neurodevelopmental disorders such as autism in the child. Pregnant women should only use Depakote for epilepsy or bipolar disorder if alternative treatment options are not feasible. Depakote should not be used for migraine prevention in women who are pregnant or women of childbearing potential without effective contraception.  

Related resources for Depakote dosages:

• Alcohol, Epilepsy Foundation
• Complex combination pharmacotherapy for bipolar disorder, Focus (American Psychiatric Publishing)
• Depakote, Abbvie
• Depakote tablets – full prescribing information, Prescribers’ Digital Reference
• Divalproex sodium, Epilepsy Foundation
• Divalproex sodium, Epocrates
• Management of bipolar disorder, American Family Physician
• Stevens-Johnson syndrome induced by a comibination of lamotrigine and valproid acid, Journal of Pharmacy & BioAllied Sciences
• Valproate for adult migraine prophylaxis, American Family Physician
• Valproate toxicity, StatPearls

Depakote is transferred to the infant in limited amounts while breastfeeding. Possible risks include liver damage in the infant. For this reason, some doctors recommend against using Depakote for conditions other than epilepsy while breastfeeding. If a patient is taking Depakote for a seizure disorder while breastfeeding, the benefits of Depakote are greater than any potential risks to the infant.