Bipolar disorder divalproex sodium

Antimanic anticonvulsants, particularly sodium valproate and carbamazepine, also have been employed prophylacticaUy in bipolar disorder. However, research supporting their long-term use remains limited, and there is growing evidence for the inferiority of carbamazepine compared to lithium (carbamazepine is not FDA-approved for bipolar disorder). Divalproex, the sodium salt of... 

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... 

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. 

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... 

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

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. 

Sovner (1989) reported that five individuals with bipolar mood disorder responded to standard treatment with divalproex sodium after failing treatment with neuroleptics and/or carbamazepine. A recent retrospective review of divalproex treatment in 28 adults with MR and severe behavior problems showed improvement (Ruedrich et ah, 1999). 

Divalproex sodium was approved by the FDA for the treatment of mania and is commonly used for all phases of bipolar disorder, as well as mood instability due to other causes. 

Tohen. M.. Baker. R.W., Milton. D.R., et al. Olanzapine versus divalproex sodium for the treatment of acute mama. Bipolar Disorders 3, 60-61, 2001. 

Solomon DA, Ryan CE, Keitner Gl, et al. A pilot study of lithium carbonate plus divalproex sodium for the continuation and maintenance treatment of patients with bipolar I disorder. J Clin Psychiatry 1997 58 95-99. 

Gracious BL, Findling RL, McNamara NK, Youngstrom EA, Calabrese JR. Elevated TSH in bipolar youth prescribed both lithium and divalproex sodium. Bipolar Disord 2001 3(Suppl l) 38-9. 

Three antiepileptic drugs have now been FDA approved as mood stabilizers for the prevention of recurring episodes of mania divalproex sodium (Depakote), extended-release carbamazepine (Equetro), and lamotrigine (Lamictal). Many of these drugs are prescribed to children for the control of epilepsy and, increasingly, for bipolar disorder. A critical question is their effect on the developing mental and emotional function of children, but there is little research on the subject (Loring, 2005). 

A 67-year-old man with bipolar disorder became confused, delirious, and manic (99). His only medications were olanzapine 10 mg/day and divalproex sodium 500 mg bd. On day 6, typical neuroleptic malignant syndrome developed. He had a fever (39.9°C), obtundation, rigidity, tremor, sweating, fluctuating pupillary diameter, labile tachycardia and hypertension, hypernatremia, and raised serum creatine kinase. Olanzapine was withdrawn and the syndrome resolved by day 12. 

Revicki DA, Paramore LC, Sommerville KW, Swann AC, Zajecka JM. Divalproex sodium versus olanzapine in the treatment of acute mania in bipolar disorder health-related quality of life and medical cost outcomes. J Clin Psychiatry 2003 64 288-94. 

Predictors of a positive response with valproate include rapid cycling, mixed episodes, comorbid panic disorder, organic mental disorders (e.g., head trauma), and mental retardation. " Low-dose valproate (125 to 500 mg/day) has been reported to be effective in reducing mood cycling in bipolar II disorder and cyclothymia. Oral loading with divalproex sodium, 20 mg/kg per day, may produce a rapid reduction in manic and psychotic symptoms within 4 days without causing major side effects, although there may be a lag time to obtain full antimanic efficacy. Development of tolerance and loss of efficacy with valproate occurs in some patients after several years of treatment." ... 

Ravindran A, Silverstone P, Lacroix D, von Schaick E, Vermeulen A Alexander J. Risperidone does not affect steady-state pharmacokinetics of divalproex sodium in patients with bipolar disorder, Clin Phamacokimt (2004) 43, 733-40,... 

In 60 patients in an 8-week, double-blind, randomized, placebo-controlled study of divalproex extended release in patients with bipolar spectrum disorders, there was nausea in 12 patients taking divalproex sodium and 7 taking placebo, sedation in 10 and 8, weight gain in six and one, abdominal pain in four and one, and abnormal dreams in four and none [313. Adverse reactions that caused withdrawal among those taking divalproex were thrombocytopenia, severe nausea, menstrual irregularity, and rash (one per patient). 

Bond DJ, Lam RW, Yatham LN. Divalproex sodium versus placebo in the treatment of acute bipolar depression a systematic review and meta-analysis. J Affect Disord 2010 124(3) 228-34. 

In a 6-month open study of divalproex sodium extended-release (15 mg/kg/day on day 1 with increases allowed to a maximum of 35 mg/kg) in 226 children and adolescents with acute mania associated with bipolar I disorder the most common adverse events were weight gain (16%), nausea (9%), and increased appetite (8%) raised plasma ammonia concentrations were non-symptomatic in all cases [340 J. 

Redden L, DelBello M, Wagner KD, Wilens TE, Malhotra S, Wozniak P, Vigna NV, Greco 4th N, Kovacs X, Abi-Saab W, Saltarelli M. Depakote ER Pediatric Mania Group. Long-term safety of divalproex sodium extended-release in children and adolescents with bipolar I disorder. J Child Adolesc Psychopharmacol 2009 19(1) 83-9. 

Geller B, Luby JL, Joshi P, Wagner KD, Emslie G, Walkup JT, et al. A randomized controlled trial of risperidone, lithium, or divalproex sodium for initial treatment of bipolar 1 disorder, manic or mixed phase, in children and adolescents. Arch Gen Psychiatry 2012 69(5) 515-28. 

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