Valproate/valproic acid efficacy

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... 

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). 

Valproic acid (valproate), discussed in detail elsewhere as an antiepileptic (see Chapter 24 Antiseizure Drugs), has been demonstrated to have antimanic effects and is now being widely used for this indication in the USA. Overall, it shows efficacy equivalent to that of lithium during the... 

Importantly, its precise mechanism of its anticonvulsant action is still not fully understood. However, it has been duly advocated that its administration specifically inhibits GABA-transaminase, and thereby enhancing the concentration of cerebral GABA. It has also been observed that a few other straight-chain saturated fatty acids i.e., lower fatty acids, such as propanoic acid, butyric acid, and pentanoic acid which are devoid of anticonvulsant characteristic features are relatively more potent and efficacious inhibitors of GABA-transaminase than is valproic acid. Furthermore, it has been adequately substantiated that there exists a rather stronger correlation between the anticonvulsant potency of valproate and other branched-chain fatty acids besides, their capability to minimise the prevailing concentration of cerebral aspartic acid (an amino acid). 

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