WARNING: LIFE THREATENING ADVERSE REACTIONS
Hepatic failure resulting in fatalities has occurred in patients receiving valproic acid and its derivatives. 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 Depakote ER is used in this patient group, it 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.
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. Liver function tests should be performed prior to therapy and at frequent intervals thereafter, especially during the first six months [see Warnings and Precautions ].
Valproate can produce teratogenic effects such as neural tube defects (e.g., spina bifida). Accordingly, the use of Depakote ER in women of childbearing potential requires that the benefits of its use be weighed against the risk of injury to the fetus. This is especially important when the treatment of a spontaneously reversible condition not ordinarily associated with permanent injury or risk of death (e.g., migraine) is contemplated [see Warnings and Precautions ].
An information sheet describing the teratogenic potential of valproate is available for patients [see Patient Counseling Information ].
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 ].
DEPAKOTE ER SUMMARY
Divalproex sodium is a stable co-ordination compound comprised of sodium valproate and valproic acid in a 1:1 molar relationship and formed during the partial neutralization of valproic acid with 0.5 equivalent of sodium hydroxide.
DEPAKOTE ER is indicated for prophylaxis of migraine headaches in adults. There is no evidence that DEPAKOTE ER is useful in the acute treatment of migraine headaches. Because valproic acid may be a hazard to the fetus, DEPAKOTE ER should be considered for women of childbearing potential only after this risk has been thoroughly discussed with the patient and weighed against the potential benefits of treatment (see WARNINGS
— Usage In Pregnancy, PRECAUTIONS
— Information for Patients).
DEPAKOTE ER is indicated as monotherapy and adjunctive therapy in the treatment of adults and children 10 years of age or older with complex partial seizures that occur either in isolation or in association with other types of seizures. DEPAKOTE ER is also indicated for use as sole and adjunctive therapy in the treatment of simple and complex absence seizures in adults and children 10 years of age or older, and adjunctively in adults and children 10 years of age or older with multiple seizure types that include absence seizures.
Simple absence is defined as very brief clouding of the sensorium or loss of consciousness accompanied by certain generalized epileptic discharges without other detectable clinical signs. Complex absence is the term used when other signs are also present.
SEE WARNINGS FOR STATEMENT REGARDING FATAL HEPATIC DYSFUNCTION.
Published Studies Related to Depakote ER (Divalproex)
Randomized, placebo-controlled trial of quetiapine XR and divalproex ER
monotherapies in the treatment of the anxious bipolar patient. 
are seldom the focus of bipolar treatment studies... CONCLUSIONS: Quetiapine XR in a dose range of 50-300 mg/day appears to reduce
Valproic acid, valproate and divalproex in the maintenance treatment of bipolar
CONCLUSIONS: Limited evidence supports the efficacy of valproate in the
Effects of divalproex on smoking cue reactivity and cessation outcomes among
smokers achieving initial abstinence. 
Divalproex, a GABA agonist, may be a useful agent in the treatment of tobacco
dependence... These findings suggest that in-treatment cue
reactivity assessment may proactively and dynamically inform ongoing treatment as
well as provide a tool for screening potential medications for smoking cessation.
Co-morbid Disruptive Behavior Disorder and Aggression Predict Functional Outcomes and Differential Response to Risperidone Versus Divalproex in Pharmacotherapy for Pediatric Bipolar Disorder. [2011.12.02]
Abstract Objective: Co-morbid diagnoses, such as disruptive behavior disorders (DBDs) and high levels of aggression, are extremely common among youth with pediatric bipolar disorder (PBD) and may interfere with treatment response; however, they have rarely been examined as predictors of response to pharmacotherapy...
Aripiprazole plus divalproex for recently manic or mixed patients with bipolar I disorder: a 6-month, randomized, placebo-controlled, double-blind maintenance trial. [2011.12.02]
OBJECTIVES: The goal of this study was to investigate the safety and efficacy in preventing relapse of a mood episode in recently manic or mixed episode patients with bipolar I disorder stabilized with aripiprazole and divalproex combination... CONCLUSIONS: In this study, relapse of mood episode occurred fewer and later for aripiprazole with divalproex treatment than divalproex monotherapy, but the differences were not statistically significant. Copyright (c) 2011 John Wiley & Sons, Ltd. Copyright (c) 2011 John Wiley & Sons, Ltd.
Clinical Trials Related to Depakote ER (Divalproex)
A Study in Stable Epilepsy Patients Comparing Brand and Generic Divalproex Sodium Extended Release Tablets [Recruiting]
Depakote Extended Release (ER) Versus Seroquel for Agitated Behaviors in Nursing Home Care Unit Patients With Dementia [Completed]
The primary objective of the study is to assess the relative efficacy of Depakote ER and
Seroquel for agitated behaviors among veterans with a dementia diagnosis residing in a
Department of Veterans Affairs (VA) nursing home care unit (NHCU). The secondary objective
of the study is to assess the relative tolerability of Depakote ER and Seroquel in this
population. The primary hypothesis is that agitated dementia patients will demonstrate a
significantly greater reduction in Cohen-Mansfield Agitation Inventory (CMAI) scores while
treated with Depakote ER compared to treatment with Seroquel.
Depakote ER in Bipolar Depression [Completed]
The purpose of this study is to examine the safety and efficacy of Depakote ER in bipolar
depression and to evaluate metabolic and GABA changes with Depakote ER administration using
PET and MRI/MRS brain imaging techniques.
Valproic Acid (Depakote[Registered Trademark]) to Treat Autoimmune Lymphoproliferative Syndrome (ALPS) [Completed]
This study will test whether valproic acid (Depakote[Registered Trademark]) can shrink
enlarged lymph glands and spleen in patients with autoimmune lymphoproliferative syndrome
(ALPS). Depakote has been used for more than 30 years for treating various medical disorders
in adults and children, including migraine headaches, seizures and psychiatric disorders. In
animal studies, it was effective in shrinking both lymph nodes and spleen in animals with
conditions similar to ALPS.
People with ALPS who are between 2 and 70 years of age and who have had an enlarged spleen
or lymph glands for at least 1 year may be eligible for this study.
Participants take Depakote as a tablet or liquid or sprinkled on food twice a day for 16
weeks. The drug dose is increased slowly over the first 3 to 4 weeks until the maximum
tolerated dose is reached. Blood tests are done at 2, 4, 6, 8 and 10 weeks after starting
the drug and 1 week after the drug is stopped to check for treatment side effects. Valproic
acid blood levels will be checked during drug escalation, half way through therapy, and just
before the end of treatment. A physical examination and CT scan (or ultrasound of the
abdomen for patients who cannot undergo CT) are done before starting treatment and at the
end of the 16-week treatment period to evaluate the response to treatment.
Patients who tolerate the treatment well and show shrinkage of the lymph glands or spleen
may be offered extended treatment for up to 1 year in consultation with their primary
physician. During the extended treatment period, blood tests are done at home every 6 to 8
weeks to monitor for drug side effects. Follow up evaluation visits are scheduled at the
NIH Clinical Center every 3 months during the extended treatment period and 3, 6, and 12
months after treatment has ended.
Bioequivalence Study of Divalproex Sodium ER Tablets, 500 mg Under Fed Conditions [Completed]
The purpose of this study is to assess the bioequivalence between Divalproex Sodium ER
Tablets 500 mg of Dr. Reddy's and Depakote ER 500 mg Tablets of Abbott Laboratories in
healthy, adult, human subjects, under fed conditions and to monitor adverse events and
ensure the safety of subjects.
Reports of Suspected Depakote ER (Divalproex) Side Effects
Drug Ineffective (10),
Weight Increased (9),
Weight Decreased (8),
Headache (8), more >>
Page last updated: 2014-11-30