WARNING: LIFE THREATENING ADVERSE REACTIONS
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 ]
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.
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). Depakote ER 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, Depakote ER should only be used after other anticonvulsants have failed. This older group of patients should be closely monitored during treatment with Depakote ER 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 ].
Valproate can cause major congenital malformations, particularly neural tube defects (e.g., spina bifida). In addition, valproate can cause decreased IQ scores following in utero exposure.
Valproate is therefore contraindicated in pregnant women treated for prophylaxis of migraine [see Contraindications (4) ]. Valproate should only be used to treat pregnant women with epilepsy or bipolar disorder if other medications have failed to control their symptoms or are otherwise unacceptable.
Valproate should not be administered to a woman of childbearing potential unless the drug is essential to the management of her medical condition. This is especially important when valproate use is considered for a condition not usually associated with permanent injury or death (e.g., migraine). Women should use effective contraception while using valproate [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 ].
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 ].
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 a valproate and is indicated for the treatment of acute manic or mixed episodes associated with bipolar disorder, with or without psychotic features. A manic episode is a distinct period of abnormally and persistently elevated, expansive, or irritable mood. Typical symptoms of mania include pressure of speech, motor hyperactivity, reduced need for sleep, flight of ideas, grandiosity, poor judgment, aggressiveness, and possible hostility. A mixed episode is characterized by the criteria for a manic episode in conjunction with those for a major depressive episode (depressed mood, loss of interest or pleasure in nearly all activities).
The efficacy of Depakote ER is based in part on studies of Depakote (divalproex sodium delayed release tablets) in this indication, and was confirmed in a 3-week trial with patients meeting DSM-IV TR criteria for bipolar I disorder, manic or mixed type, who were hospitalized for acute mania [see Clinical Studies ].
The effectiveness of valproate for long-term use in mania, i.e., more than 3 weeks, has not been demonstrated in controlled clinical trials. Therefore, healthcare providers who elect to use Depakote ER for extended periods should continually reevaluate the long-term risk-benefits of the drug for the individual patient.
Depakote ER is indicated as monotherapy and adjunctive therapy in the treatment of adult patients and pediatric patients down to the age of 10 years 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.
Depakote ER is indicated for prophylaxis of migraine headaches. There is no evidence that Depakote ER is useful in the acute treatment of migraine headaches.
Because of the risk to the fetus of decreased IQ, neural tube defects, and other major congenital malformations, which may occur very early in pregnancy, valproate should not be administered to a woman of childbearing potential unless the drug is essential to the management of her medical condition [see Warnings and Precautions (5.2, 5.3, 5.4)
, Use in Specific Populations , and Patient Counseling Information ].
Depakote ER is contraindicated for prophylaxis of migraine headaches in women who are pregnant.
Published Studies Related to Depakote (Divalproex)
Valproic acid, valproate and divalproex in the maintenance treatment of bipolar
CONCLUSIONS: Limited evidence supports the efficacy of valproate in the
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
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.
Chronic divalproex sodium use and brain atrophy in Alzheimer disease. [2011.09.27]
OBJECTIVE: We evaluated the effect of the divalproex sodium formulation of valproic acid on brain volumes using MRI in people with mild to moderate Alzheimer disease (AD) and assessed for changes associated with behavioral and cognitive effects... CONCLUSIONS: Divalproex treatment was associated with accelerated brain volume loss over 1 year and perhaps with greater cognitive impairment. The long-term clinical effects of these changes are not known.
Chronic divalproex sodium to attenuate agitation and clinical progression of Alzheimer disease. [2011.08]
CONTEXT: Agitation and psychosis are common in Alzheimer disease and cause considerable morbidity. We attempted to delay or to prevent agitation and psychosis with the use of divalproex sodium (valproate). OBJECTIVE: To determine whether treatment with valproate could delay or prevent emergence of agitation or psychosis... CONCLUSION: Valproate treatment did not delay emergence of agitation or psychosis or slow cognitive or functional decline in patients with moderate Alzheimer disease and was associated with significant toxic effects.
Clinical Trials Related to Depakote (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 (Divalproex) Side Effects
Emotional Distress (119),
Foetal Exposure During Pregnancy (118),
Physical Disability (116),
Loss of Employment (67), more >>
PATIENT REVIEWS / RATINGS / COMMENTS
Based on a total of 2 ratings/reviews, Depakote has an overall score of 7. The effectiveness score is 10 and the side effect score is 6. The scores are on ten point scale: 10 - best, 1 - worst.
Depakote review by 53 year old female patient
|Overall rating:|| || |
|Effectiveness:|| || Highly Effective|
|Side effects:|| || Mild Side Effects|
|Condition / reason:|| || Bi-polar disorder|
|Dosage & duration:|| || 450 mg at night taken every day for the period of 10 years|
|Other conditions:|| || depression|
|Other drugs taken:|| || Prozac, Lithium|
|Benefits:|| || Made the patient feel normal pretty much. |
|Side effects:|| || Depakote made me sleepy at first, so we switched the dose to nighttime instead of day and night. Prozac, I have some ear pain from it. Lithium upsets my stomach if I take too much at one time, so I don't. I take one pill in the morning, and one in the evening. |
|Comments:|| || I see a psychiatrist regularly. He originally prescribed me Prozac many years ago, when I started seeing him after my husband left me abruptly alone with a three-year old son. I felt like I was losing my mind. The prozac helped calm me, but it was really when I began taking the Depakote that I began to feel good about myself, and anchored enough to take care of my son, who is now 19. |
Depakote review by 57 year old female patient
|Overall rating:|| || |
|Effectiveness:|| || Highly Effective|
|Side effects:|| || Severe Side Effects|
|Condition / reason:|| || Seizure disorder|
|Dosage & duration:|| || can't recall (dosage frequency: daily) for the period of 2 years|
|Other conditions:|| || Major Depression, migraine, hypothyroidism|
|Other drugs taken:|| || Synthroid, Remeron, Klonepin|
|Benefits:|| || The med. controlled my seizure disorder.|
|Side effects:|| || The side effects were terrible. I endured daily moderate to severe headaches which I had to treat with high dosage of ibuprofen and a 50 lb. weight gain over two months on a 5'2" frame with no change in my diet. I could not shake the weight until I discontinued taking the med.|
|Comments:|| || Treatment was to take the med. daily. It controlled the seizure disorder but the side effects were too much for me. I talked to the physician after two years and said it's gotta go. He then prescribed Lamictal and I lost 40 lbs. in one month--simply by stopping the Depakote. |
Page last updated: 2014-11-30