Divalproex anticonvulsant

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). 

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). 

According to the Expert Consensus Panel for Mental Retardation Rush and Frances, (2000), the mainstays of the pharmacological treatment of acute mania or bipolar disorder in adults are anticonvulsant medications (divalproex, valproic acid, or carbamazepine) or lithium. Both divalproex or valproic acid and lithium were preferred treatments for classic, euphoric manic episodes. Divalproex or valproic acid was preferred over lithium and carbamazepine for mixed or dysphoric manic episodes and rapid-cycling mania. For depressive episodes associated with bipolar disorder, the addition of an antidepressant (SSRI, bupropion, or venlafaxine) was recommended. According to the Expert Consensus Panel, the presence of MR does not affect the choice of medication for these psychiatric disorders in adults. 

In the Expert Consensus survey (Rush and Frances, 2000), respondents were asked to rate which classes of medication may be helpful for treating patients with severe and persistent physical aggression and those who destroyed property. The atypical antipsychotics were rated most highly, followed by anticonvulsant/ mood stabilizer. These were followed (with much lower priority) by antidepressants and beta-blockers. Among the atypical antipsychotics, risperidone was rated most highly, followed by olanzapine others had much lower ratings. Divalproex or valproic acid and carbamazepine were rated highest of the mood stabi-... 

Sodium valproate is useful in the control of most seizure types and has the shortest half-life of the commonly used anticonvulsants (4—15 hours) a slowly absorbed form of the drug, divalproex sodium, is sometimes preferred. Valproate is relatively free from cognitive and behavioural side effects, but alopecia and weight gain frequently occur. The most severe side effect is idiosyncratic hepatotoxicity and pancreatitis, particularly in younger patients. However, these side effects are more frequent in patients taking valproate as a co-medication with other anticonvulsants. 

The program is straightforward in its call to start drugging children in the absence of any scientific basis In the absence of treatment data, treatment of childhood bipolar illness is modeled on that of adults. Even if the child shows no signs of psychosis, the most toxic adult drugs are recommended For non-psychotic children, in descending order, treatment should be tried with lithium, divalproex, atypical antipsychotic, combining any of these approaches, and other anticonvulsants plus atypical antipsychotics or conventional antipsychotic. ... 

Since first reported by Cade in 1949, lithium has been the most frequently studied and used drug for the treatment of bipolar disorder. Recent trends in the United States have shifted to the use of anticonvulsants—mostly divalproex and valproic acid—although the rationale for this switch in emphasis arguably stands on tenuous scientific grounds. 

Mood stabilizers can be used as augmentation therapy in cases of partial response to antidepressant therapy, especially those with prominent irritability or anger. Anticonvulsants (thought to exert their mechanism in part through antikindling effects) have been effective in treating PTSD. In a retrospective review topiramate reduced nightmares and flashbacks. Divalproex sodium was effective in an open trial. ... 

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... 

Valproic acid (Depakene or Depakote [divalproex sodium]) is a structurally unique anticonvulsant. It is used for the treatment of absence seizures, partial complex, and generalized seizure disorders and is a secondary agent for refractory status epilepticus. It is also commonly used for the prophylaxis and treatment of acute manic episodes and other affective disorders, migraine prophylaxis, and chronic pain syndromes. 

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