Divalproex sodium

Reoux JP, Saxon AJ, Malte CA, et al Divalproex sodium in alcohol withdrawal a randomized douhle-hlind placeho-controlled clinical trial. Alcohol Clin Exp Res 25 1324-1329,2001... 

Divalproex sodium Depakote Enteric-coated, 750-3000 mg/day (20-60 mg/kg Monotherapy or in... 

Divalproex sodium is comprised of sodium valproate and valproic acid. The delayed-release and extended-release formulations are converted in the small intestine into valproic add, which is the systemically absorbed form. It was developed as an antiepileptic drug, but also has efficacy for mood stabilization and migraine headaches. It is FDA-approved for the treatment of the manic phase of bipolar disorder. It is generally equal in efficacy to lithium and some other drugs for bipolar mania. It has particular utility in bipolar disorder patients with rapid cycling, mixed mood features, and substance abuse comorbidity. Although not FDA-approved for relapse prevention, studies support this use, and it is widely prescribed for maintenance therapy. Divalproex can be used as monotherapy or in combination with lithium or an antipsychotic drug.31... 

Baetz, M., Bowen, R. C. Efficacy of divalproex sodium in patients with panic disorder and mood instability who have not responded to conventional therapy. Can. J. Psych. 43 73-77,1998. 

The enteric-coated tablet divalproex sodium causes fewer GI side effects. It is metabolized in the gut to valproic acid. When switching from Depakote to Depakote-ER, the dose should be increased by 14% to 20%. Depakote ER may be given once daily. 

Valproic acid/divalproex sodium 500-1,500 mg/day in divided doses... 

Valproic acid and divalproex sodium (a 1 1 molar combination of valproate sodium and valproic acid) can reduce the frequency, severity, and duration of headaches by at least 50% in up to 65% of migraineurs. 

Side effects of valproic acid and divalproex sodium include nausea (less common with divalproex sodium and gradual dosing titration), tremor,... 

Lithium, divalproex sodium (valproate), aripiprazole, olanzapine, que-tiapine, risperidone, and ziprasidone are currently approved by the FDA for treatment of acute mania in bipolar disorder. Lithium, olanzapine, and lamotrigine are approved for maintenance treatment of bipolar disorder. Quetiapine is the only antipsychotic that is FDA approved for bipolar depression. 

Divalproex sodium (sodium valproate) is now the most prescribed mood stabilizer in the United States. It is FDA approved only for the treatment of acute manic or mixed episodes, but it is often used as maintenance monotherapy for bipolar disorder. 

Divalproex sodium Depakote Enteric-coated, delayed-... 

In contrast to the large number of studies that have investigated lithium as a maintenance treatment for bipolar disorder, relatively few studies have been made of divalproex sodium, despite its widespread use in the acute treatment of mania. There is evidence from one placebo-controlled study in which lithium was compared with divalproex sodium that the latter drug was better tolerated but that the prevention of relapse did not differ between the drugs. It would therefore appear that a switch to divalproex sodium may be particularly useful in bipolar patients who are experiencing... 

Divalproex Sodium Depakote 125, 250, 500 mg delayed-release tablets... 

Tablets, delayed-release 125, 250, and 500 mg (as divalproex sodium) Rx) Depakote (Abbott)...

Mania (divalproex sodium delayed-release tablets) Trea men of manic episodes associated with bipolar disorder. 

Migraine (divalproex sodium delayed-release and ER tablets) As prophylaxis of migraine headaches. 

Oral products Bedtime administration may minimize effects of CNS depression. Gl irritation may be minimized by taking with food or by slowly increasing the dose. Delayed-release divalproex sodium may reduce the incidence of irritative Gl effects. Swallow the extended-release tablets whole do not crush or chew. Swallow the valproic acid capsules without chewing to avoid local irritation of the mouth and throat. 

Adjunctive therapy - Divalproex sodium or valproic acid may be added to the patient s regimen at a dosage of 10 to 15 mg/kg/day. The dosage may be increased by 5 to 10 mg/kg/wk to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses less than 60 mg/kg/day. If satisfactory clinical response has not been achieved, measure plasma levels to determine whether they are in the usually accepted therapeutic range (50 to 100 mcg/mL). If the total daily dose exceeds 250 mg, administer in divided doses. 

In epileptic patients previously receiving valproic acid therapy, initiate divalproex sodium at the same daily dose and dosing schedule. After the patient is stabilized on divalproex tablets, a dosing schedule of 2 or 3 times/day may be elected in selected patients. 

Mania (divalproex sodium delayed-release tablets) 750 mg/day in divided doses increase as rapidly as possible to achieve the lowest therapeutic dose that produces the desired clinical effect or the desired range of plasma concentrations (trough plasma concentrations 50 to 125 mcg/mL). Maximum concentrations generally were achieved within 14 days. Maximum recommended dosage is 60 mg/kg/day. 

Divalproex sodium delayed-release tablets-The starting dose is 250 mg orally twice/day. Some patients may benefit from doses up to 1,000 mg/day. There is no evidence that higher doses lead to greater efficacy. 

Pharmacology This group includes valproic acid, sodium valproate (the sodium salt), and divalproex sodium (a compound containing equal proportions of valproic acid and sodium valproate). Regardless of form, dosage is expressed as valproic acid equivalents. 

Absorption - /a pro c acid is rapidly and almost completely absorbed from the Gl tract. Absorption of the drug is delayed but not decreased by administration with meals administration of the drug with milk products does not affect the rate or degree of absorption. The bioavailability of valproate from divalproex sodium delayed-release tablets and capsules containing coated particles has been shown to be equivalent to that of valproic acid capsules. 

Children See Warning Box. The safety and efficacy of divalproex sodium for the treatment of acute mania has not been studied in individuals younger than 18 years of age. Divalproex sodium extended-release tablets are not recommended in children. Use of valproate sodium injection has not been studied in children below 2 years of age. 

Migraine - The safety and efficacy of divalproex sodium for the prophylaxis of migraines has not been studied in individuals under 16 years of age. 

Brand Name(s) (divalproex sodium) Depacon, Depakote, Depakote ER, Depakote Sprinkle... 

Kowatch, R.A., Suppes, T., Carmody, T.J., Bucci, J.P., Hume, J.H., Kromelis, M., Emslie, G.J., Weinberg, W.A., and Rush, A.J. (2000) Effect size of lithium, divalproex sodium, and carbama-zepine in children and adolescents with bipolar disorder. / Am Acad Child Adolesc Psychiatry 39 713-720. 

Carbamazepine (CBZ) and divalproex sodium (DVP) are the most common anticonvulsant agents prescribed for adult BD (Bowden et ah, 1994) Post et ah, 1998b) and pediatric epileptic disorders (Trimble, 1990 Dunn et al., 1998). As a consequence of their documented efficacy in these populations, their use has been extended to pediatric behavioral and mood disorders (Biederman et ah, 1998). We review here their mechanisms of action, pharmacokinetics, side effects, and pediatric uses. The multiple cytochrome P450 (CYB)-mediated potential drug interactions of CBZ and DVP are not covered in detail in this chapter. For a comprehensive review of this subjects the reader is referred to a recent publication by Flockhart and Oesterheld (2000). 

BUN, blood urea nitrogen CBC, complete blood cell count CBZ, carbamazepine DVP, divalproex sodium EKG, electrocardiogram SIADH, syndrome of inappropriate secretion of antidiuretic hormone TSH, thyroid-stimulating hormone. 

Valproic acid, valproate sodium, and (DVP) are carboxylic acid-derivative anticonvulsants. Divalproex sodium is a stable coordination compound consisting of valproic acid and valproate sodium in a 1 1 molar ratio (AHFS, 2000). It is a pro-drug of valproate, dissociating into valproate in the GI tract (AHFS, 2000), and a simple branched-chain carboxylic acid (w-dipropylacetic acid) with antiepileptic activity against a variety of types of seizures (Beydoun et al., 1997). Divalproex sodium has been approved for treating adults with simple and complex absence seizures (Mattson et al., 1992), and for mania. It has shown efficacy across a broad spectrum of BD subtypes (i.e., pure mania, mixed mania, and rapid cycling) (Pope et al., 1991 Bowden et al., 1994). 

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