Last reviewed 2026-04-20 · How we verify

Depakene (valproic acid)

Broad-spectrum anticonvulsant that enhances GABA activity, blocks sodium and calcium channels, and inhibits histone deacetylase.

Valproic acid (Depakene/Depakote) is the broadest-spectrum antiepileptic drug, approved in 1978. Also first-line for bipolar mania and migraine prevention. Available generically. BLACK BOX WARNING: hepatotoxicity and teratogenicity (contraindicated in pregnancy for migraine/bipolar).

At a glance

Mechanism of action

Valproic acid has multiple mechanisms of action: it increases brain GABA levels, blocks voltage-gated sodium channels, and inhibits T-type calcium channels. It is one of the broadest-spectrum antiepileptic drugs, effective for nearly all seizure types. Also a first-line mood stabilizer for bipolar disorder. Carries significant teratogenicity risk (neural tube defects) — contraindicated in pregnancy.

Approved indications

• Absence seizure
• Bipolar affective disorder, current episode manic
• Epilepsy
• Epilepsy characterized by intractable complex partial seizures
• Migraine Prevention

Boxed warnings

• BOXED WARNING Hepatotoxicity General Population: Hepatic failure resulting in fatalities has occurred in patients receiving valproate and its derivatives. These incidents usually have occurred during the first six months of treatment. Serious or fatal hepatotoxicity may be preceded by non-specific symptoms such as malaise, weakness, lethargy, facial edema, anorexia, and vomiting. In patients with epilepsy, a loss of seizure control may also occur. Patients should be monitored closely for appearance of these symptoms. Serum liver tests should be performed prior to therapy and at frequent intervals thereafter, especially during the first six months [see Warnings and Precautions ( 5.1 )] . Children under the age of two years are at a considerably increased risk of developing fatal hepatotoxicity, especially those on multiple anticonvulsants, those with congenital metabolic disorders, those with severe seizure disorders accompanied by mental retardation, and those with organic brain disease. When valproic acid products are used in this patient group, they should be used with extreme caution and as a sole agent. The benefits of therapy should be weighed against the risks. The incidence of fatal hepatotoxicity decreases considerably in progressively older patient groups. Patients with Mitochondrial Disease: There is an increased risk of valproate-induced acute liver failure and resultant deaths in patients with hereditary neurometabolic syndromes caused by DNA mutations of the mitochondrial DNA Polymerase γ (POLG) gene (e.g. Alpers Huttenlocher Syndrome). Valproic acid is contraindicated in patients known to have mitochondrial disorders caused by POLG mutations and children under two years of age who are clinically suspected of having a mitochondrial disorder [see Contraindications ( 4 )] . In patients over two years of age who are clinically suspected of having a hereditary mitochondrial disease, valproic acid should only be used after other anticonvulsants have failed. This older group of patients should be closely monitored during treatment with valproic acid for the development of acute liver injury with regular clinical assessments and serum liver testing. POLG mutation screening should be performed in accordance with current clinical practice [see Warnings and Precautions ( 5.1 )] . Fetal Risk Valproate can cause major congenital malformations, particularly neural tube defects (e.g., spina bifida). In addition, valproate can cause decreased IQ scores and neurodevelopmental disorders following in utero exposure. Valproate is therefore contraindicated for prophylaxis of migraine headaches in pregnant women and in women of childbearing potential who are not using effective contraception [see Contraindications ( 4 )] . Valproate should not be used to treat women with epilepsy or bipolar disorder who are pregnant or who plan to become pregnant unless other medications have failed to provide adequate symptom control or are otherwise unacceptable. Valproate should not be administered to a woman of childbearing potential unless other medications have failed to provide adequate symptom control or are otherwise unacceptable. In such situations, effective contraception should be used [see Warnings and Precautions ( 5.2 , 5.3 , 5.4 )] . A Medication Guide describing the risks of valproate is available for patients [see Patient Counseling Information ( 17 )] . Pancreatitis Cases of life-threatening pancreatitis have been reported in both children and adults receiving valproate. Some of the cases have been described as hemorrhagic with a rapid progression from initial symptoms to death. Cases have been reported shortly after initial use as well as after several years of use. Patients and guardians should be warned that abdominal pain, nausea, vomiting, and/or anorexia can be symptoms of pancreatitis that require prompt medical evaluation. If pancreatitis is diagnosed, valproate should ordinarily be discontinued. Alternative treatment for the underlying medical condition should be initiated as clinically indicated [see Warnings and Precautions ( 5.5 )] . See full prescribing information for complete boxed warning. Hepatotoxicity, including fatalities, usually during first 6 months of treatment. Children under the age of two years and patients with mitochondrial disorders are at higher risk. Monitor patients closely, and perform serum liver testing prior to therapy and at frequent intervals thereafter ( 5.1 ) Fetal Risk, particularly neural tube defects, other major malformations, and decreased IQ ( 5.2 , 5.3 , 5.4 ) Pancreatitis, including fatal hemorrhagic cases ( 5.5 )

Common side effects

• Tremor
• Nausea
• Somnolence
• Vomiting
• Asthenia
• Dizziness
• Thrombocytopenia
• Alopecia
• Diarrhea
• Abdominal Pain
• Headache
• Infection

Serious adverse events

• Hepatotoxicity
• Birth Defects/Teratogenicity
• Pancreatitis
• Thrombocytopenia
• Ataxia
• Nystagmus

Key clinical trials

• Valproic Acid and Dihydroergotamine as Abortive Therapy in Pediatric Migraine: An Open-Label Randomized Trial. (Phase 2)
• Treatment of Acute Myelogenous Leukemia With the Histone Deacetylase Inhibitor Valproic Cid in Combination With All-trans Retinoic Acid (ATRA) and Low Dose Cytarabine (Phase 1)
• A Double Blind Trial Of Divalproex Sodium For Affective Lability And Alcohol Use Following Traumatic Brain Injury (NA)
• Phase I-II Study of Low Dose CdA Combined With Valproic Acid (VPA) in Previously Treated B-cell Chronic Lymphocytic Leukemia (CLL) Patients (Phase 1)
• A Study of the Safety and Efficacy of Depakote ER Plus an Atypical Antipsychotic Vs. an Atypical Antipsychotic Alone in the Treatment of Schizophrenia (Phase 2)
• Overnight Versus Progressive Conversion of Multiple Daily Dose Enteric-Coated Divalproex to Once-Daily Divalproex Extended Release: Which Strategy is Better Tolerated by Patients With Intellectual Dis (NA)
• Phase I/II Study of Intravenous Infusion of Tetra-o-Methyl Nordihydroguaiaretic Acid (EM-1421) in Subjects With Recurrent High Grade Glioma (Phase 1)
• PLA General Hospital (Phase 1)

Primary sources

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Competitive intelligence

For the full competitive landscape — auto-detected comparators, recent regulatory actions across the set, upcoming PDUFA, patent timeline, sponsor landscape:

• Depakene CI brief — competitive landscape report
• Depakene updates RSS · CI watch RSS
• Generic (originally Abbott/AbbVie) portfolio CI