Lithium antiepileptic drugs

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... 

Turning to the pharmacotherapy for mania, for decades lithium was the only effective drug treatment. More recently, a number of antiepileptic drugs including carba maze pine, lamotrigine and valproate have been shown to also act as mood stabilisers and are becoming established for the treatment and prophylaxis of both unipolar mania and bipolar manic depressive disorders. 

Exposure to the fetus in the first 2 weeks after conception may have an all or nothing effect (i.e., could destroy the embryo or have no ill effect). Exposure during the period of organogenesis (18 to 60 days postconception) may result in structural anomalies (e.g., methotrexate, cyclophosphamide, diethylstilbestrol, lithium, retinoids, thalidomide, certain antiepileptic drugs, and coumarin derivative). 

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... 

For low therapeutic/toxic drugs such as lithium, this might prove to be an explanation of the reduction in efficacy seen at the end of the menstrual cycle, when these hormone levels fall (Conrad and Hamilton, 1986). It might also explain the reduction in efficacy of other central nervous system drugs such as antiepileptics (Shavit et al., 1984 Roscizeweska et al., 1986) and antimigraine medications, seen with the fluctuation of the menstrual cycle (Gengo et al., 1984). 

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