*An off-label use of a medication is a use that is not FDA-approved. Prescribers can decide to use a medication off-label because, in their professional judgment, they believe it may offer a benefit to someone.
Depakote side effects are possible when taking the medication to treat bipolar disorder. Common side effects associated with Depakote can be broad, affecting the digestive tract, causing headaches, dizziness, belly and back pain, tremors, and more. Severe side effects associated with Depakote include pancreatitis, liver damage, allergic reactions, bleeding problems, and a potential increase in suicidal behavior or ideation. Some side effects can remain long-term.
If you are considering Depakote or want to discuss your current medication treatment with a provider, online psychiatry platforms, such as Talkiatry and Brightside Health are a good place to start. Their providers offer assessments and prescription consultation, and can answer any questions you have about Depakote side effects.
Boxed Warning: Divalproex (Depakote) Risk of side effects that can be life-threatening
Divalproex, the active ingredient in Depakote, has a black box warning. This is the most serious type of warning from the Food and Drug Administration (FDA). Divalproex can increase the risk of side effects that can be life-threatening. These side effects include liver toxicity, pancreatitis, and risks to an unborn fetus. You should talk with your doctor about serious risks with divalproex and any other medications before starting treatment.
Key Takeaways
Common Depakote side effects may include diarrhea, dizziness, nausea, and drowsiness.
Your provider can help you determine next steps if your side effects persist longer than a few weeks or seem to get worse. They may recommend a change in dosage, timing of dosage, or medication.
Medication adjustments, self care practices, and therapy are all ways to help you cope with Depakote side effects.
If you are considering Depakote or an alternative, an evaluation from a medical provider is a good place to start. Many online psychiatry platforms offer online assessments and medication management, such as Talkiatry or Brightside Health.
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Common Depakote Side Effects
Depakote can cause several common side effects for some who take it. Initial side effects may go away on their own, but some may require medical attention. Contact your provider if any side effects persist or get worse.
Depakote is a delayed-release medication that may be given in divided doses during the day. It is also available as Depakote ER, an extended-release version that is given once a day. This article will focus primarily on Depakote. If you have questions about Depakote ER, talk with your provider.
Common side effects of Depakote include:*1,2
- Nausea
- Drowsiness
- Dizziness
- Vomiting
- Accidental injury
- Weakness
- Pain
- Upset stomach
- Rash
*All medications, including Depakote, can cause side effects that can be mild or serious. This is not a comprehensive list of all possible side effects. You should talk with your doctor about any questions you have and understand the potential side effects and benefits of any medication.
Serious Depakote Side Effects
Some Depakote side effects can be persistent or serious. If these side effects appear, seek immediate medical attention.
- Pancreatitis
- Bleeding problems
- Liver damage
- Suicidal thoughts and behaviors
- Increased levels of ammonia
- Birth defects, decreased IQ, and neurodevelopmental disorders
- Hypothermia – drop in core body temperature
- Drowsiness in older adults
*All medications, including Depakote, can cause side effects that can be mild or serious. This is not a comprehensive list of all possible side effects. You should talk with your doctor about any questions you have and understand the potential side effects and benefits of any medication.
It is possible for Depakote to cause long-term side effects. There are warnings associated with the medication for the risk of liver damage. This includes liver failure and pancreatitis (swelling of the pancreas), among others. These serious side effects can occur in people who have just started taking Depakote or those who have been on Depakote for years.
Liver damage usually occurs within the first six months of treatment. Pancreatitis can happen shortly after starting Depakote as well as after several years of usage. These can be long-term complications that may be life-threatening. If you show symptoms of pancreatitis or liver damage, seek immediate medical care.
*All medications, including Depakote, can cause side effects that can be mild or serious. This is not a comprehensive list of all possible side effects. You should talk with your doctor about any questions you have and to understand the potential side effects and benefits of any medication.
What Are the Risks & Warnings for Depakote?
Suicidal Thoughts & Behaviors
All antiepileptic drugs, including Depakote, have increased risk for suicidal thoughts and behavior. Anyone taking Depakote should be monitored for such thoughts, no matter their age.
Bleeding Disorders
Taking Depakote can cause a dangerous drop in platelets known as thrombocytopenia. This can lead to dangerous bleeding, especially in those patients with a history of bleeding disorders.
Liver Disease
Liver failure and death (hepatotoxicity) have been reported in patients taking Depakote. It usually happens within the first six months of treatment and is marked by symptoms like weakness, vomiting, and facial swelling.
Pregnancy
Taking Depakote while pregnant can cause serious fetal harm and defects. Based on data, taking Depakote while pregnant can increase the risk of fetal abnormalities four times that of pregnant parents using other anticonvulsant medications. Studies have shown that children born to pregnant parents exposed to Depakote during pregnancy have lowered IQ. Parents who may become pregnant should use effective contraception while taking Depakote.
Pancreatitis
Cases of life-threatening pancreatitis have been reported in people taking Depakote. Pancreatitis presents as abdominal pain, nausea, vomiting, and/or anorexia, and any of these symptoms should be taken seriously.
Complications With Urea Cycle Disorders
No one with known urea cycle disorders or a familial history of the disorder should take Depakote.
Allergic Reactions
For some people taking Depakote, an allergic reaction may occur which may be dangerous.
Severe allergic reactions to Depakote can include:
- Breathing problems
- Swelling
- Rash/hives
If you experience wheezing, difficulty breathing, or swelling in the throat, seek immediate medical help.
Severe Drug Hypersensitivity
It’s possible for Depakote to cause serious skin reactions, such as drug reactions with eosinophilia and systemic symptoms (DRESS). If you experience blistering or discoloration of your skin, it is important to seek emergency treatment or call 911 right away.
Drug Interactions
Taking certain medications, herbs, or supplements alongside Depakote can change how Depakote works in your body or increase the risk for serious side effects. Do not start, stop, or change the dosage of any medicines without your doctor’s approval.
Substances you should avoid using while taking Depakote include:*
- Carbamazepine, phenytoin, phenobarbital, primidone, and rifampin (medications that cause the liver to break down other drugs more quickly)
- Topiramate
- CBD products
- Aspirin
- Contraceptives containing estrogen
- Lamotrigine
- Alcohol
*This is not a comprehensive list of medications that interact with Depakote. Be sure to talk with your doctor or pharmacist about any prescription or over the counter medications you take, as well as supplements, herbs, and teas.
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Important Things to Know About Taking Depakote
Before starting Depakote, you’ll want to know what to expect during your first weeks of treatment. Talk with your prescriber about your dosage, how to take your medication, precautions, potential side effects, and what to do if side effects become a problem.
How Long Does It Take for Depakote to Work?
With bipolar disorder, it may take several weeks to see a change in symptoms.3 Keep taking Depakote even if you do not see results so your body can have time to get used to the medication.
Can Depakote Make You Feel Worse at First?
Yes, some people may experience uncomfortable side effects when starting Depakote such as nausea, drowsiness, and dizziness. Depakote can also increase the risk of suicidal thoughts and behaviors in some people. If you experience worsened symptoms or side effects of any kind, contact your provider immediately.
What Happens If I Miss a Dose?
If you miss a dose, take the missed dose as soon as you remember. However, if it is almost time for your next dose, skip the missed dose and take your scheduled dose. Then continue following your normal Depakote dosing schedule. Do not double up on doses to make up for any missed ones.
It is important to continue taking Depakote and to talk to your provider or pharmacist if you have questions about the medication. Do not stop taking this medication without discussing it with your provider.
Who Experiences Side Effects More?
Some who take Depakote have a greater risk of experiencing side effects. While it’s hard to predict who may not respond well to a certain medication, certain patient populations should be cautious with Depakote.
Discuss your health history and any conditions you have with your provider when considering medication like Depakote. This information will help your provider select the most suitable medication for you.
Those Using Other Medications
Depakote can have harmful interactions with medications and other substances. This may include serious reactions requiring medical care or reduced effectiveness of Depakote, the other medication, or both.
Those using certain medications or substances also have a higher risk of side effects with Depakote, such as:1,2
- Hepatic enzyme-inducing drugs (medications that cause the liver to break down other drugs more quickly)
- Topiramate
- CBD products
- Aspirin
- Contraceptives containing estrogen
- Lamotrigine
- Alcohol
This is not a complete list of possible interactions with Depakote. Consult with your healthcare provider before combining Depakote with any over-the-counter medications, prescription medications, or herbal supplements to ensure safety and effectiveness.
Those With Certain Health Risks
Those with certain health concerns or conditions are at higher risk of side effects. Your provider can help you determine if Depakote is suitable for you or if you should avoid it.
Individuals with an increased risk for experiencing side effects include those who:
- Have a history of liver problems
- Are pregnant or plan to be pregnant
- Are breastfeeding or plan to breastfeed
- Prior allergic reactions to Depakote and its components
- Have a risk of pancreatitis
- Have a history of urea cycle disorder
- Have a history of suicidal ideation
- Have a history of bleeding disorders
This is not a complete list of possible health risks associated with Depakote. Discuss your full health history before considering Depakote as a treatment.
Here are other groups of people who need to consider Xanax with caution:
Older Adults
Older adults are at greater risk of side effects while on Depakote. Those 65 years and older are more likely to have tremors, drowsiness, pain, accidental injury, and infection while taking Depakote.1,2
Pregnant & Breastfeeding Parents
Depakote may cause birth defects, decreased IQ, and neurodevelopmental disorders when taken during pregnancy. Those who are pregnant or may become pregnant should avoid taking Depakote unless other medications have failed to manage their condition and there are no other alternatives.
Depakote can pass into breast milk and may cause harm. If you are breastfeeding or plan to breastfeed, talk to your provider about the risks of taking Depakote.1,2
How to Cope With Common Depakote Side Effects
There are ways to cope with the most common Depakote side effects*. Many may go away on their own during the first few weeks. If any side effects persist or worsen, contact your provider for guidance.
Tremors
Tremors are a common side effect associated with Depakote, with women and adults over age 65 being more commonly affected. This side effect may be dose-related.1,2 If you experience tremors while on Depakote, contact your healthcare provider. Potential treatments for tremors caused by Depakote are medication adjustments and the addition of other medications to manage the tremors.
Digestive Side Effects
There are several side effects affecting digestion, including constipation, diarrhea, nausea, upset stomach, vomiting, and stomach pain. Talk to your doctor if you are experiencing these side effects. They can determine what adjustments to make to your treatment or if your symptoms are a sign of bigger problems that need to be addressed.
Drowsiness and Dizziness
Drowsiness and dizziness may be tolerable or a temporary event as the body gets used to the medication, but tolerance depends on other conditions a person may have. These side effects can be especially dangerous for those who are at a higher risk of falls and injury. To reduce your risk, make sure to get a full night’s rest and avoid taking any stimulants like medications or caffeine near bedtime. If you continue to deal with these side effects, contact your provider.
Headache
Headaches are a side effect associated with Depakote, being one of the few side effects that is considered common for the medication. This side effect reportedly occurred in more than 5% of patients on Depakote.1,2 If you experience headaches, you may be able to take over-the-counter pain relievers to manage the symptoms. If you continue to experience headaches or they worsen, contact a doctor for further help.
Sexual Side Effects
It is possible that Depakote can cause sexual side effects in men and women, though they were not reported in clinical trials. Antiseizure drugs are known to have side effects involving the endocrine system, which affects sexual functioning. Depakote may affect hormone levels and cause issues such as menstrual disturbances, low libido, and reduced fertility.4
*All medications, including Depakote, can cause side effects which can be mild or serious. This is not a comprehensive list of all possible side effects. You should talk with your doctor about any questions you have and to understand the potential side effects and benefits of any medication.
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More Ways to Manage Depakote Side Effects
Here are more ways to cope with and reduce the impact of Depakote side effects.
Practice Good Sleep Hygiene
Your sleep habits can make a difference when adjusting to your new medication. Try to wake up and go to bed at the same time every day. Make sure your sleep environment is dark and comfortable as well.
Also, Depakote can slow your thinking and motor skills and may affect your vision. Be aware of how Depakote affects your mental alertness and motor skills while taking it. Older adults can be more vulnerable to drowsiness with Depakote. Do not drive a car, operate dangerous machinery, or do dangerous activities until you know how Depakote affects you.1,2
Healthy Lifestyle Activities
Healthy lifestyle habits provide the support your body and mind need as they adjust to your new medication. Focus on eating well, getting enough sleep, being physically active, and staying connected socially.
Follow a Daily Routine
Follow your normal daily routine as you start taking your new Depakote prescription. Keeping a regular schedule will reduce stress on your body and mind as you adjust to the effects of Depakote. Also, be sure you’re following your provider’s instructions exactly, paying close attention to the timing.
Consider Therapy
Psychotherapy can help you develop strategies to manage the impact of side effects. For in-person therapy, your primary care provider or insurance company can provide referrals in your local area. Or, you may get a recommendation from a family member or friend.
To find an online therapist, an online therapist directory is a great starting point. Many online psychiatry platforms, such as Talkiatry and Brightside Health, also offer therapy services.
Should I Stop Taking Depakote If I Start Feeling Side Effects?
No, do not stop taking Depakote if you start feeling side effects. Stopping Depakote abruptly can lead to serious side effects like seizures that don’t stop, which can be life threatening. If you want to consider stopping Depakote or changing your dosage, talk to your provider first. Do not adjust your dosage on your own. Your provider will tell you how to safely reduce your dose.1,2
When Should I Call My Doctor About Depakote Side Effects?
If your side effects continue or get worse, talk to your provider right away. Side effects are a top reason people stop taking a medication, and stopping Depakote without medical guidance can be unsafe. Your provider will discuss your Depakote side effects, treatment options, and your next steps.
Some side effects are manageable and may go away on their own. However, some may continue for as long as you take the medication. Medications can cause side effects even when taken correctly. Serious side effects from Depakote include bleeding problems, liver damage, suicidal thoughts and behaviors, and increased levels of ammonia in the body. These can be life-threatening and require immediate medical care.
When Should I Seek an Alternative to Depakote Due to Side Effects?
You may notice some side effects of Depakote appearing within the first few weeks, though some may appear sooner. Each person has a unique response to medication so this timeframe may vary. Initial side effects may go away on their own, and others may continue or worsen while taking the medication.
If you’re considering a change in your medication, talk with your provider. There are many Depakote alternatives available and they can help you determine which one may be a good fit. Several types of mood stabilizers can help reduce bipolar disorder symptoms. It’s important to learn about the potential risks and benefits of each option.
Other anticonvulsant medications, such as Lamictal and Tegretol, can be used as alternatives to Depakote for bipolar disorder. These medications are effective mood stabilizers, helping to reduce symptoms of mania and controlling mood changes.
Atypical antipsychotics, such as Latuda and Seroquel, are also used as mood stabilizers for bipolar disorder. They are helpful for people who have psychotic symptoms as part of their manic or depressive episodes. These medications reduce agitation, delusions, hallucinations, paranoia, and confusion. They are often used in combination with another mood stabilizer.
How to Get a Prescription for Depakote or Alternative Medications
To get a prescription for Depakote or an alternative in person, your first step is to have your symptoms evaluated. Your primary care provider, who may be a physician, nurse practitioner, or PA, can help you start this process. They’ll also determine if a referral to a specialist may be helpful. Based on their assessment, they’ll decide if Depakote or an alternative should be part of your treatment plan.
To get a prescription for Depakote or an alternative online, you’ll also begin with an evaluation from a platform that prescribes anticonvulsants like Depakote. We have carefully reviewed Talkiatry and Brightside and determined they are both good places for such an evaluation.
Their providers can also prescribe mood stabilizers, such as Depakote or an alternative, if they deem the medication helpful for your symptoms. Both platforms offer assessments and prescription management.
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Questions to Ask Your Provider
Your provider will discuss possible side effects of Depakote with you. They will highlight any side effects that may appear when starting Depakote and those that require medical treatment. They can also discuss what to do if side effects persist or become difficult to manage.
Also, many online psychiatry services make it convenient to get mental health care for bipolar disorder. You’ll get a mental health evaluation, diagnosis, and personalized treatment plan from one of their providers. Some platforms also allow you to change providers, if needed.
Questions to ask your care team about Depakote side effects may include:
- How often should I come for checkups for my Depakote prescription?
- What common side effects will I likely experience when I start my Depakote medication?
- How long will the medication’s side effects last?
- Am I at risk for more severe side effects if I am already taking medication for anxiety, depression, or other mental health conditions?
- When should I reach out to you if I am experiencing side effects?
- What should I do if Depakote does not work for me?
- What will happen if I suddenly stop my medication?
- What is the best dosage to ensure fewer side effects?
- Are there drugs I am taking that could have negative interactions?
- Can the side effects of Depakote interfere with my daily activities, such as work, school, or driving?
- Will I need any regular monitoring (blood tests, weight checks, etc..) while taking Depakote?
- What are the long-term benefits and risks for taking Depakote?
- Are there any dietary considerations I should be aware of while taking Depakote?
- Can anticonvulsants be used in combination with other medications or therapies for a more comprehensive treatment approach?
- Is there a risk of tardive dyskinesia (involuntary muscle movements) with long-term use of this medication?
Prescriber’s Tips
Before starting Depakote, your provider will give you important instructions. They’ll discuss how to take your medication, what to avoid when taking it, and how to store it properly. They’ll also talk through what to do if side effects occur. Follow these tips for safe and effective use of Depakote.
- Take your medication as prescribed unless your prescriber tells you otherwise. Keeping a consistent dosing schedule reduces the chance of unwanted side effects.1,2
- Do not stop Depakote without first talking to a healthcare provider. Stopping Depakote suddenly can cause serious problems. If you have epilepsy, stopping a seizure medicine suddenly can cause seizures that will not stop (status epilepticus).1,2
- Take your medication at the same time each day. Doing so can help you remember to take it and make your treatment as effective as possible. Your healthcare provider can determine the best time to take your medication based on how you respond to it.
- Depakote may increase the risk of suicidal thoughts and behaviors and symptoms of depression. Tell your prescriber right away if you have any new or worsening depression, suicidal thoughts or behavior, and any unusual changes in your mood or behavior.1
- Do not drink alcohol while taking Depakote. Depakote and alcohol can affect each other causing side effects such as sleepiness and dizziness. Taking Depakote with these substances can make your drowsiness or dizziness worse.
- Tell your prescriber about all medications and supplements you take, including over-the-counter treatments. Many over-the-counter medications and supplements can interact with prescription medications.
Frequently Asked Questions
What Is Depakote & How Is it Used?
Depakote contains the active ingredient divalproex sodium and is a medication FDA-approved for the treatment of manic episodes associated with bipolar disorder, epilepsy, and migraine prevention.1,2
How Does Depakote Work?
Depakote works by increasing the amount of a chemical called GABA in the brain, which is thought to balance the chemicals in the body, but the exact mechanism of how it works is unknown. It is formulated as a delayed-release tablet, a delayed-release sprinkle capsule, and an extended-release tablet which is sold as both brand and generic versions. 2
How Does Depakote Make You Feel?
During the first few weeks of taking Depakote, the medication is building up in your body. This may trigger side effects for some people. It takes several weeks for Depakote to start working fully and you may not notice any difference in your symptoms yet.
Does the Risk of Side Effects Increase With Higher Doses of Depakote?
There is a potential increase in risk when the dosage of Depakote is increased. The clinical research studies did not directly compare the different doses for any of the formulations, and if that increase in dosage correlated to an increased risk of side effects. If you experience a side effect, consult with your doctor or seek immediate care if it is serious. 1,2
Can Depakote Cause Weight Gain?
Depakote may cause weight gain. It is a common side effect associated with the medication, along with weight loss.1,2 Weight change is usually due to appetite changes in patients. Drug-induced weight gain from Depakote can lead to patients not being adherent to their therapy. If you experience this side effect and it is a problem for you, then contact your doctor to discuss your options. Keep in mind that weight loss can be a sign of liver damage which requires immediate medical care.
Can I Take Depakote While Pregnant?
Depakote may cause fetal harm when taken by those who are pregnant. It may cause neural tube defects and other structural abnormalities. Those who are pregnant or may become pregnant should avoid taking this medication unless other medications have failed to manage their condition and no other alternatives exist. Discuss your treatment options with your provider prior to or during pregnancy.1,2
Do Older People Have a Higher Risk of Side Effects on Depakote?
Yes, older patients can be at greater risk of side effects while on Depakote. In clinical trials, those 65 years and older were more likely to report tremors, drowsiness, pain, accidental injury, and infection while on Depakote. It isn’t clear whether these events mean that this group is at additional risk or if they were a result of pre-existing medical conditions and other medications taken at the same time as Depakote. Consult your provider if you experience these problems, as they may reduce your dosage or discontinue the medication altogether. 1,2
Should I Stop Taking Depakote If I Experience Side Effects?
No, do not stop taking Depakote unless your provider tells you to do so. Stopping Depakote abruptly can lead to serious side effects like seizures that don’t stop, which can be life threatening. 1,2
ChoosingTherapy.com strives to provide our readers with mental health content that is accurate and actionable. We have high standards for what can be cited within our articles. Acceptable sources include government agencies, universities and colleges, scholarly journals, industry and professional associations, and other high-integrity sources of mental health journalism. Learn more by reviewing our full editorial policy.
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Depakote- divalproex sodium tablet, delayed release. (May 9, 2025). DailyMed.nlm.nih.gov. Retrieved from https://dailymed.nlm.nih.gov/dailymed/lookup.cfm
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Depakote ER – divalproex sodium tablet, extended release. (May 1, 2025). DailyMed.nlm.nih.gov. Retrieved from https://dailymed.nlm.nih.gov/dailymed/lookup.cfm
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Valproate (Depakote) | NAMI: National Alliance on Mental Illness. (n.d.). Retrieved from https://www.nami.org/Valproate-(Depakote)
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Svalheim, S., Sveberg, L., Mochol, M., & Taubøll, E. (2015). Interactions between antiepileptic drugs and hormones. Seizure, 28, 12–17. Retrieved from https://doi.org/10.1016/j.seizure.2015.02.022
We regularly update the articles on ChoosingTherapy.com to ensure we continue to reflect scientific consensus on the topics we cover, to incorporate new research into our articles, and to better answer our audience’s questions. When our content undergoes a significant revision, we summarize the changes that were made and the date on which they occurred. We also record the authors and medical reviewers who contributed to previous versions of the article. Read more about our editorial policies here.
Author: No Change
Reviewer: No Change
Primary updates: Added “Key Takeaways” feature. Edited for clarity. Condensed “What is Depakote & How Is It Used?” and moved to FAQs. Revised and condensed “Common Side Effects of Depakote” and “Severe Side Effects of Depakote” sections. Revised and moved content from “Allergic Reactions” and “Depakote Serious Side Effects” sections into new “What Are the Warnings & Risks of Depakote?” feature. Condensed and moved “Long-term Side Effects” section to “Serious Depakote Side Effects” section. Added new sections “Important Things to Know About Taking Depakote” and “Who Experiences Side Effects More?”. Revised and moved FAQ section to the end. Revised and retitled “How to Manage Side Effects” to “How to Cope With Common Side Effects of Depakote”. Added new sections “More Ways to Manage Depakote Side Effects”, “Should I Stop Taking Depakote If I Start Feeling Side Effects?”, “When Should I Seek an Alternative to Depakote Due to Side Effects?”, “How to Get a Prescription for Depakote or Alternative Medications” and all included subsections. Retitled “Questions to Ask Your Healthcare Provider About Depakote Side Effects” to “Questions to Ask Your Provider”. Replaced “Final Thoughts” with “Prescriber’s Tips” feature. Removed “For Further Reading”.
Author: Robyn Tyman, PharmD
Medical Reviewer: Dena Westphalen, PharmD
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