Divalproex (Depakote) for Bipolar Disorder: Uses, Dosage, Blood Levels, and Safety
Divalproex (brand name Depakote) is a mood stabilizer FDA-approved to treat manic episodes of bipolar disorder, as well as epilepsy and migraine prevention. It works relatively quickly for mania and is often continued long-term to prevent relapse. It also requires more monitoring than many psychiatric medications: blood levels, liver tests, and blood counts. It carries boxed warnings for liver failure, pancreatitis, and serious harm to a developing baby, which makes it a poor choice for anyone who is or could become pregnant.
Anticonvulsant mood stabilizer (valproate)
About 50–125 mcg/mL
Mania and mixed episodes
Levels, liver tests, blood counts
What Is Divalproex Used For?
- Manic episodes of bipolar disorder, its FDA-approved psychiatric use (bipolar disorder treatment)
- Epilepsy (several seizure types)
- Migraine prevention
- Off-label: long-term prevention of bipolar mood episodes, and mixed or rapid-cycling presentations
Divalproex is better at treating and preventing mania than depression. People with frequent bipolar depression often need another medication alongside it or instead of it.
How Does Divalproex Work?
Divalproex is converted to valproate in the body. It’s thought to stabilize mood by increasing GABA, the brain’s main calming messenger, and by dampening overactive nerve signaling. The exact mechanism in bipolar disorder isn’t fully understood.
Divalproex Dosage and Blood Levels
| Step | Mania (delayed-release tablets) |
|---|---|
| Starting dose | 750 mg per day, in divided doses |
| Adjusting | Increased as quickly as tolerated toward clinical response |
| Target blood level | About 50–125 mcg/mL (trough), as used in trials |
| Maximum | 60 mg/kg per day |
Source: Depakote FDA prescribing information. Extended-release (Depakote ER) is dosed differently and is not interchangeable milligram for milligram.
- Blood levels are drawn as a trough, just before your next dose, usually after several days on a steady dose.
- Taking it with food can reduce stomach upset.
- Swallow tablets whole; don’t crush or chew delayed- or extended-release forms.
Monitoring on Divalproex
Lab work is part of using this medication safely:
- Valproate level to confirm you’re in the effective range and not too high
- Liver function tests before starting and periodically, especially in the first 6 months
- Complete blood count with platelets, since low platelets are dose-related and more likely at levels above about 110 mcg/mL in women and 135 mcg/mL in men
- Ammonia, if you develop unexplained confusion, sluggishness, or vomiting
- Weight, and for women, menstrual changes and pregnancy status
Boxed Warnings
Liver failure. Serious or fatal liver injury can occur, usually in the first 6 months. Risk is highest in children under 2 and people with certain mitochondrial disorders (POLG). Report loss of appetite, vomiting, unusual tiredness, yellowing skin or eyes, or swelling.
Harm to an unborn baby. Valproate causes major birth defects, especially neural tube defects, at about four times the rate of other anti-seizure monotherapies, and lowers IQ: children exposed during pregnancy had a mean IQ of 97 at age 6 versus 108 with lamotrigine.
Pancreatitis. Rare but potentially life-threatening. Seek care for severe belly pain, nausea, or vomiting.
Women who could become pregnant
Because of the pregnancy risks, divalproex is generally avoided in women who are pregnant or could become pregnant unless other treatments haven’t worked. If it’s used, effective birth control is essential, and pregnancy plans should be discussed well in advance. Valproate has also been linked to polycystic ovary-type changes in some women.
Divalproex Side Effects
In mania trials, these side effects were more common than with placebo:
| Side effect | Depakote | Placebo |
|---|---|---|
| Nausea | 22% | 15% |
| Drowsiness | 19% | 12% |
| Dizziness | 12% | 4% |
| Vomiting | 12% | 3% |
| Weakness | 10% | 7% |
| Rash | 6% | 3% |
Source: Depakote FDA prescribing information, 3-week mania trials.
With longer use, weight gain, tremor, and hair thinning are common. Low platelets can cause easy bruising or bleeding. Like other antiepileptic drugs, it carries a warning about suicidal thoughts.
Who Should Not Take Divalproex
- Liver disease or significant liver dysfunction
- Known POLG-related mitochondrial disorders
- Urea cycle disorders
- Allergy to divalproex, valproate, or valproic acid
- Pregnancy, or possible pregnancy without effective contraception, in most situations
Important interactions
- Lamotrigine: valproate raises lamotrigine’s half-life from about 26 to 70 hours, so lamotrigine is started at half the usual pace to reduce rash risk. See lamotrigine (Lamictal).
- Carbapenem antibiotics (meropenem, ertapenem, imipenem) can drop valproate levels sharply. Tell any hospital team you take divalproex.
- Topiramate increases the risk of high ammonia.
- Aspirin and blood thinners can affect valproate levels and bleeding risk.
- Alcohol adds to sedation and strain on the liver. Avoid it.
Stopping: don’t stop suddenly. Taper with your prescriber to avoid relapse of mood symptoms, or seizures in people with epilepsy.
Divalproex vs. Other Mood Stabilizers
| Divalproex | Lamotrigine | Quetiapine | |
|---|---|---|---|
| Acute mania | Approved | Not effective | Approved |
| Bipolar depression | Limited | Prevention | Approved |
| Routine labs | Levels, liver, blood counts | Not required | Glucose, lipids |
| Pregnancy | Generally avoided | Often preferred option | Case by case |
See our guide to quetiapine (Seroquel).
How We Approach Divalproex at Samz Mental Health
- Reserve it for situations where it fits best, such as mania, mixed episodes, or when other mood stabilizers haven’t worked
- Discuss pregnancy potential openly before starting, and consider alternatives first when relevant
- Arrange baseline and follow-up labs through your primary care provider or a local lab, including levels, liver tests, and blood counts
- Review results and adjust through ongoing medication management
Can You Get Divalproex Prescribed Online?
Yes. Divalproex isn’t a controlled substance, so it can be prescribed through telehealth when appropriate, with required blood tests drawn locally. Samz Mental Health treats bipolar disorder by video for adults physically located in Texas, New York, Florida, Colorado, Washington, Maryland, New Hampshire, New Mexico, and Iowa. If you’re experiencing severe mania with unsafe behavior or psychosis, in-person emergency care comes first.
In-network with Aetna, Cigna, UnitedHealthcare, Optum, and Carelon Behavioral Health. See insurance details.
Frequently Asked Questions About Depakote
What is Depakote used for?
Bipolar mania, epilepsy, and migraine prevention; it’s also often used long-term to prevent bipolar episodes.
What is the Depakote dose for bipolar mania?
Usually 750 mg a day to start, adjusted toward a blood level of about 50 to 125 mcg/mL.
What blood tests are needed on Depakote?
Valproate levels, liver tests, and blood counts with platelets, plus ammonia if symptoms suggest it.
Is Depakote safe in pregnancy?
No. It causes birth defects and lower IQ and is generally avoided in anyone who is or could become pregnant.
Does Depakote cause weight gain?
Often, yes, along with tremor and hair thinning.
What are the boxed warnings for Depakote?
Liver failure, harm to an unborn baby, and pancreatitis.
Can Depakote be taken with lamotrigine?
Yes, but lamotrigine must be started lower and slower.
Can I get Depakote prescribed online?
Yes, with blood tests drawn locally. Samz Mental Health treats bipolar disorder by video in nine states.
Talk to a Provider About Bipolar Treatment
Book a video evaluation with a board-certified psychiatric nurse practitioner. Same-day appointments available. No referral needed.
References
- Depakote (divalproex sodium) prescribing information. Drugs.com professional label; also on DailyMed.
Medical disclaimer: This page is for education and is not a substitute for a personal medical evaluation. Don’t start, stop, or change any medication without talking to your prescriber. If you’re in crisis or thinking about harming yourself, call or text 988 (Suicide & Crisis Lifeline) or call 911.