divalproex
Divalproex (Depakote) is a prescription medication that's used alone or in combination with other medications to treat certain types of seizures. It can also be used to prevent migraines and treat bipolar disorder. Divalproex (Depakote) comes in delayed-release (DR) and extended-release (ER) tablets, as well as sprinkle capsules. You take it by mouth, typically once or twice daily, depending on the formulation. Divalproex (Depakote) can cause changes in weight, both in weight loss and weight gain. Don't suddenly stop taking this medication since it can raise your risk of withdrawal symptoms, including seizures.
What is Divalproex (Depakote)?
What is Divalproex (Depakote) used for?
Bipolar disorder
Seizures (focal impaired awareness seizure, absence seizure)
Migraine prevention
How Divalproex (Depakote) works
Divalproex (Depakote) is an antiepileptic. It's not exactly clear how this medication works to prevent migraines or treat mania episodes in bipolar. But in order to control seizures, divalproex (Depakote) signals your brain to make more of a chemical called gamma-aminobutyric acid (GABA). GABA helps to reduce the bursts of activity in your brain, which prevents seizures.
Drug Facts
More on Divalproex (Depakote) essentials
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What are the side effects of Divalproex (Depakote)?
Common Side Effects
- Nausea (22%)
- Excess sleepiness (19%)
- Dizziness (12%)
- Vomiting (12%)
- Accidental injury (11%)
- Low energy (10%)
- Nausea (48%)
- Headache (31%)
- Feeling weak (27%)
- Vomiting (27%)
- Tremor (25%)
- Dizziness (25%)
- Stomach pain (23%)
- Nausea (31%)
- Feeling weak (20%)
- Excessive sleepiness (17%)
- Indigestion (13%)
- Diarrhea (12%)
- Dizziness (12%)
- Vomiting (11%)
Other Side Effects
- Double or blurry vision
- Diarrhea
- Changes in appetite
- Body aches, cough, and other flu-like symptoms
- Rash
- Fever
- Constipation
- Movements problems
- Feeling more emotional
- Trouble remembering
- Hair loss
- Weight loss
- Back pain
Serious Side Effects
- Suicidal thoughts or behaviors
- Severe allergic reactions: fever, rash, extreme tiredness, body aches, mouth sores, blisters, trouble breathing
- Serious liver problems: nausea, vomiting, not feeling hungry, pain in the right side of the stomach, yellowing of the whites of the eyes or skin, dark-colored urine, light-colored stool
- Extremely high blood ammonia levels: fatigue, poor mental alertness, vomiting
- Inflamed pancreas: upper stomach pain, fever, nausea, vomiting
- Serious bleeds: bleeding that's difficult to stop, vomiting blood, blood in the urine or stool, "coffee-ground" stool
- Extreme drop in body temperature: shivering, feeling tired, feeling confused, slurred speech, coma
Source: DailyMed
More on Divalproex (Depakote) side effects
The following side effects have also been reported
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur:
More common
Black, tarry stools
bleeding gums
bloating or swelling of the face, arms, hands, lower legs, or feet
blood in the urine or stools
chills
confusion
crying
delusions of persecution, mistrust, suspiciousness, or combativeness
difficult or labored breathing
dysphoria
false beliefs that cannot be changed by facts
false or unusual sense of well-being
feeling of unreality
general feeling of discomfort or illness
headache
hoarseness
joint pain
loss of appetite
lower back or side pain
mental depression
muscle aches and pains
nervousness
painful or difficult urination
pinpoint red spots on the skin
poor insight and judgment
problems with memory or speech
quick to react or overreact emotionally
rapid weight gain
rapidly changing moods
sense of detachment from self or body
shakiness in the legs, arms, hands, or feet
shivering
sleepiness or unusual drowsiness
sweating
tightness in the chest
tingling of the hands or feet
trembling or shaking of the hands or feet
trouble recognizing objects
trouble sleeping
trouble thinking and planning
trouble walking
unusual bleeding or bruising
unusual tiredness or weakness
unusual weight gain or loss
vomiting
Less common
Abnormal dreams
absence of or decrease in body movement
bloody nose
blurred vision
bruising burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
change in personality
change in walking and balance
changes in patterns and rhythms of speech
cloudy urine
clumsiness or unsteadiness
cold sweats
dark urine
deep or fast breathing with dizziness
degenerative disease of the joint
difficulty with moving
dizziness
dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
excessive muscle tone
fast, irregular, pounding, or racing heartbeat or pulse
feeling of warmth or heat
flushing or redness of the skin, especially on the face and neck
frequent urge to urinate
heavy non-menstrual vaginal bleeding
increased need to urinate
indigestion
lack of coordination
large, flat, blue or purplish patches in the skin
leg cramps
lip smacking or puckering
loss of bladder control
loss of strength or energy
multiple swollen and inflamed skin lesions
muscle pain or stiffness
muscle tension or tightness
normal menstrual bleeding occurring earlier, possibly lasting longer than expected
numbness of the feet, hands and around mouth
pains in the stomach, side, or abdomen, possibly radiating to the back
passing urine more often
pounding in the ears
puffing of the cheeks
rapid or worm-like movements of the tongue
rapid weight gain
restlessness
seeing, hearing, or feeling things that are not there
shakiness and unsteady walk
slurred speech
small red or purple spots on the skin
sweating
swollen joints
trouble with speaking
twitching
uncontrolled chewing movements
uncontrolled movements of the arms and legs
unsteadiness, trembling, or other problems with muscle control or coordination
vomiting of blood or material that looks like coffee grounds
yellow eyes or skin
Incidence not known
Aggression
bladder pain
blistering, peeling, loosening of the skin
blisters on the skin
bone pain, tenderness, or aching
chest discomfort
cloudy urine
decrease in height
decreased urine output
difficulty swallowing
feeling that others are watching you or controlling your behavior
feeling that others can hear your thoughts
feeling, seeing, or hearing things that are not there
increased sensitivity of the skin to sunlight
increased thirst
irritability
joint or muscle pain
loss of balance control
loss of consciousness
mask-like face
pain in the back, ribs, arms, or legs
pain or swelling in the arms or legs without any injury
puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
red skin lesions, often with a purple center
red, irritated eyes
redness or other discoloration of the skin
seizures
severe mood or mental changes
severe sunburn
shuffling walk
slow heartbeat
slowed movements
slurred speech
sores, ulcers, or white spots in the mouth or on the lips
stiffness of the arms and legs
swelling of the face, ankles, or hands
swollen or painful glands
tic-like (jerky) movements of the head, face, mouth, and neck
unusual behavior
Get emergency help immediately if any of the following symptoms of overdose occur:
Symptoms of overdose
Change in consciousness
fainting
loss of consciousness
slow or irregular heartbeat
Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
More common
Belching
body aches or pain
change in vision
congestion
continuing ringing or buzzing or other unexplained noise in the ears
hair loss or thinning of the hair
hearing loss
impaired vision
lack or loss of strength
loss of memory
problems with memory
seeing double
tender, swollen glands in the neck
uncontrolled eye movements
voice changes
Less common
Absent, missed, or irregular menstrual periods
burning, dry, or itching eyes
change in taste or bad unusual or unpleasant (after) taste
coin-shaped lesions on the skin
cough producing mucus
cramps
dandruff
discharge or excessive tearing
excess air or gas in the stomach or bowels
feeling of constant movement of self or surroundings
full feeling
increased appetite
itching of the vagina or genital area
loss of bowel control
neck pain
oily skin
pain during sexual intercourse
pain or tenderness around the eyes and cheekbones
passing gas
rash with flat lesions or small raised lesions on the skin
redness or swelling in the ear
redness, pain, swelling of the eye, eyelid, or inner lining of the eyelid
redness, swelling, or soreness of the tongue
sensation of spinning
stiff neck
stopping of menstrual bleeding
thick, white vaginal discharge with no odor or with a mild odor
Incidence not known
Breast enlargement
changes in hair color or texture
discoloration of the fingernails or toenails
increased hair growth, especially on the face
unexpected or excess milk flow from the breasts
Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.
Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
Pros and cons of Divalproex (Depakote)
Pros
Available as a lower-cost generic
Dose can be adjusted based on your response
Available in various forms: delayed-release tablets, sprinkle capsules, and extended-release tablets
Can be used on its own or with other medications to control seizures
Cons
Can prevent migraines from happening, but it won't help if you have a migraine attack
Interacts with many medications, such as phenytoin (Dilantin)
Can’t take while pregnant
Requires regular blood work and lab tests to make sure your liver is healthy
Pharmacist tips for Divalproex (Depakote)
Different formulations of divalproex (Depakote) might have different directions and age-cut offs. If you (or your child) are just starting or switching to a different formulation of divalproex (Depakote), double check with your provider that the formulation, dose, and directions are appropriate.
If you want to stop treatment with divalproex (Depakote), talk with your provider. Don't stop taking divalproex (Depakote) suddenly, especially if you've a history of seizures. Doing so can raise your risk for seizures that won't stop. Your provider can help you stop this medication safely by lowering your dose slowly over time.
Your provider might ask you to get blood tests done routinely while you’re taking divalproex (Depakote). This is so that they can watch out for your liver health. Tell your provider right away if you've symptoms of liver damage, such as feeling sleepy, upper right stomach pain, yellowing of the skin or eyes, or dark urine.
In some rare cases, divalproex (Depakote) can cause high blood ammonia levels. Let your provider know if you experience symptoms of fatigue, poor mental alertness, or vomiting.
If you're able to become pregnant, make sure to use birth control, like condoms, while taking divalproex (Depakote). Don't take divalproex (Depakote) if you're pregnant since it can cause harm to the unborn baby. If you're pregnant or thinking of getting pregnant during treatment, contact your provider right away. Your provider might prescribe you a different medication that's safer during pregnancy.
Let your provider know if you experience symptoms of depression or worsening mood while taking divalproex (Depakote).
Let your provider know if you're taking over-the-counter pain medications (e.g., aspirin) or if you're on blood thinners such as warfarin (Coumadin). These medications can interact with divalproex (Depakote) and put you at a higher risk for bleeding or more side effects from divalproex (Depakote).
Divalproex (Depakote) can sometimes cause rash and other severe skin reactions. If you have a rash, skin pain, blisters, or skin peeling, talk with your provider right away.
Avoid drinking alcohol while taking divalproex (Depakote) because it can worsen some of the side effects such as sleepiness and dizziness. In particular, divalproex (Depakote) can cause extreme drowsiness in people over 65 years old, which can raise the risk of falling. Tell your provider if you're experiencing more drowsiness than usual. Your provider might start you at a lower dose of this medication.
If you notice what looks like a pill in your stool, contact your provider. This could be a sign your body isn't absorbing divalproex (Depakote) correctly.
Directions for divalproex (Depakote) sprinkle capsules: If you have trouble swallowing, you can open up the capsule and sprinkle the content on soft food, such as applesauce or yogurt. Make sure to hold the capsule so the end marked "This end up" is upright. Twist open the capsule over soft food to prevent spilling. Take the entire mixture immediately after mixing. Avoid chewing the mixture since this can change how the medication gets absorbed. Rinse down the content with water to help make sure all of the medication is swallowed.
Frequently asked questions about Divalproex (Depakote)
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What are the risks and warnings for Divalproex (Depakote)?
Divalproex (Depakote) can cause some serious health issues. This risk may be even higher for certain groups. If this worries you, talk to your doctor or pharmacist about other options.
Liver problems
Risk factors: Children under 2 years old | Taking multiple anti-seizure medications | Severe seizure problems | Certain genetic metabolic problems | Current or history of liver problems
Divalproex (Depakote) can cause liver problems that can be life-threatening. These problems are more common in the first 6 months of treatment. Your risk is higher if you've a history of liver problems. If you've any of the risk factors listed above, please talk with your provider so they can decide whether divalproex (Depakote) is a safe treatment for you.
Your provider will order blood tests before you start and while you're taking divalproex (Depakote) to check your liver health. If you experience symptoms of liver problems, such as feeling sleepy, upper right stomach pain, yellowing of the skin or eyes, or dark urine, please talk with your provider right away.
Serious birth defects
Don't take divalproex (Depakote) if you're pregnant. Divalproex (Depakote) can cause serious problems to unborn babies, such as neural tube defects or lower mental ability, if taken by mothers during pregnancy. If you're able to become pregnant, your provider might recommend you to use a form of birth control or take folic acid while you're taking divalproex (Depakote). If you become pregnant while taking divalproex (Depakote), let your provider know right away. Don't stop taking this medication on your own since it might raise your risk of seizures. You’re also encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This registry monitors and collects information about your and your baby’s health. Learn more about this registry by calling 1-888-233-2334.
Serious pancreas problems
Though rare, people who took divalproex (Depakote) have reported inflammation of the pancreas (pancreatitis). This can happen at any point during treatment with this medication. Some common symptoms of an inflamed pancreas are upper stomach pain, fever, nausea, and vomiting. If you start to feel any of these symptoms, contact your provider right away.
Suicidal behavior and thoughts
Risk factors: History of depression | Taking anti-epileptics
As with many other anti-epileptics, divalproex (Depakote) can raise the risk of suicidal thoughts or actions as early as 1 week after starting treatment. The risk is higher if you've had suicidal thoughts or actions in the past. Let your friends and family know to watch out for new or worsening signs of depression or other changes in mood or behavior. Call your provider right away if any suicidal thoughts or actions occur.
Lower blood cell counts
Risk factors: Taking higher doses of divalproex (Depakote) | Taking medications that lower blood cell counts
Though extremely rare, some people developed lower platelet count while taking divalproex (Depakote). This can put you at higher risk for bleeds. Your provider will typically require lab work before and while you're taking this medication to make sure it's safe for you. Let your provider know if you've symptoms of bleeding, such as abnormal bruising.
Higher ammonia level in blood
Risk factors: History of metabolic disorders | Taking topiramate | Low body temperature
Divalproex (Depakote) can cause ammonia to build up in your body, especially if it's taken with topiramate. This can cause you to become more tired, unable to concentrate, or vomit. In some cases, you might also experience a drop in body temperature when your ammonia level is high. High levels of ammonia in the blood can lead to brain damage, which can be dangerous. Get medical attention right away if you notice any of these symptoms. Don't take divalproex (Depakote) if you've been told that you have a history of metabolic disorders that raise ammonia levels (e.g., urea cycle disorders).
Severe skin and allergic reactions
Divalproex (Depakote) can sometimes cause rash and other severe skin reactions. In some cases, these severe allergic reactions, such as drug reaction with eosinophilia and systemic symptoms (DRESS), have happened with or without a rash. Although these reactions are rare, they can cause organ failure or blood problems. Let your provider know if you experience these reactions because they'll need to stop divalproex (Depakote) treatment and also talk with you about safer options to treat your condition. If you have a rash, blisters on your lips, skin peeling, skin pain, mouth sores, or high fever, get medical help immediately.
Interaction with other medications
Some medications can interfere with how your body gets rid of divalproex (Depakote). This can affect the amount of divalproex (Depakote) in your body, how well it works, and the risk of side effects.
For example, taking divalproex (Depakote) with carbapenem antibiotics can lower the amount of divalproex (Depakote) in your body and potentially cause divalproex (Depakote) to not work as well. On the other hand, taking divalproex (Depakote) with aspirin can raise the amount of divalproex (Depakote) in your body and potentially lead to more side effects. As a result, your provider will monitor your blood works closely when you take these medications together.
Likewise, divalproex (Depakote) can also interfere with how your body gets rid of other medications and raise your risk of side effects from those medications. For example, taking divalproex (Depakote) can raise the amount of lamotrigine (Lamictal) in your body. Taking a lower dose of lamotrigine (Lamictal) might help reduce your risk of serious side effects like rash.
For your safety, let your provider or pharmacist know what other medications you’re taking before and while taking divalproex (Depakote) so they can help you check for interactions.
Divalproex (Depakote) dosage forms
Typical dosing for Divalproex (Depakote)
Bipolar disorder (adults only)
Extended-release (ER) tablets: Your provider will determine the dose based on your body weight. The typical starting dose is 25 mg/kg by mouth once daily. Your provider will raise your dose quickly to help control your mood better. The maximum dose is 60 mg/kg daily.
Delayed-release (DR) tablets: The typical starting dose is 750 mg daily, split into smaller doses and taken by mouth throughout the day. Your provider will raise your dose quickly to help control your mood better. The maximum dose is 60 mg/kg (based on body weight) daily.
Migraine prevention (adults only)
ER tablets: The typical starting dose is 500 mg by mouth once daily. The maximum dose is 1000 mg once daily.
DR tablets: The typical starting dose is 250 mg by mouth twice daily. The maximum daily dose is 1000 mg.
Seizures (adults and children ages 10 years or older)
ER tablets, DR tablets, and sprinkle capsules: Your provider will determine the dose based on your body weight. The typical starting dose ranges from 10 mg/kg to 15 mg/kg by mouth per day, depending on what type of seizure you have. Your provider will raise your dose weekly as needed to better control the seizures. The maximum daily dose is 60 mg/kg.
Your dose might differ if you're an older adult.
More on Divalproex (Depakote) dosage forms
Interactions between Divalproex (Depakote) and other drugs
More on Divalproex (Depakote) interactions
Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
- Calcifediol
- Calcium Oxybate
- Cannabidiol
- Carvedilol
- Cisplatin
- Doripenem
- Ertapenem
- Estradiol
- Ethinyl Estradiol
- Imipenem
- Lamotrigine
- Lumateperone
- Magnesium Oxybate
- Meropenem
- Mestranol
- Orlistat
- Pexidartinib
- Potassium Oxybate
- Primidone
- Propofol
- Sodium Oxybate
- Vorinostat
- Warfarin
Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
- Acyclovir
- Aspirin
- Betamipron
- Carbamazepine
- Cholestyramine
- Clomipramine
- Erythromycin
- Ethosuximide
- Felbamate
- Fosphenytoin
- Ginkgo
- Lopinavir
- Lorazepam
- Mefloquine
- Nimodipine
- Nortriptyline
- Olanzapine
- Oxcarbazepine
- Panipenem
- Phenobarbital
- Phenytoin
- Rifampin
- Rifapentine
- Risperidone
- Ritonavir
- Rufinamide
- Topiramate
- Valacyclovir
- Zidovudine
How much does Divalproex (Depakote) cost?
Divalproex (Depakote) contraindications
History of liver problems or certain liver diseases (e.g., urea cycle disorders)
Have certain genetic disorders (e.g., Alpers-Huttenlocher Syndrome)
Children under 2 years old at risk of certain genetic disorders (e.g., POLG (DNA polymerase gamma)) disorder)
People who are pregnant or can become pregnant but aren't using contraception
Treatment of migraine
What are alternatives to Divalproex (Depakote)?
Bipolar disorder
Seizures (focal impaired awareness seizure, absence seizure)
Migraine prevention
Seizures (partial seizures, tonic-clonic seizures, Lennox-Gastaut syndrome)
Migraine prevention
Seizures (partial seizures, tonic-clonic seizures)
Seizures of Lennox-Gastaut syndrome - immediate-release only
Bipolar disorder - immediate-release only
What is the latest news about Divalproex (Depakote)?
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References
Best studies we foundAli, R., et al. (2023). Hyperammonemia. StatPearls.
Allen, M. J., et al. (2023). GABA receptor. StatPearls.
Amneal Pharmaceuticals LLC. (2023). DIVALPROEX SODIUM tablet, extended release [package insert]. DailyMed.
Aurobindo Pharma Limited. (2023). DIVALPROEX SODIUM - divalproex sodium tablet, delayed release [package insert]. DailyMed.
Canning, J. E., et al. (2012). Lithium and valproate-induced tremors. Mental Health Clinician.
Centers for Disease Control and Prevention. (2023). Facts about neural tube defects.
Kanner, A. M., et al. (2018). Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new-onset epilepsy Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology.
MedlinePlus. (2011). Alpers-Huttenlocher syndrome.
MedlinePlus. (2023). POLG gene.
Mew, N. A., et al. (2017). Urea cycle disorders overview. GeneReviews.
Perucca, E. (2002). Pharmacological and Therapeutic Properties of Valproate. CNS Drugs.
Stone, W. L., et al. (2023). Urea cycle disorders. StatPearls.
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