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. 2002;4(5):200. doi: 10.4088/pcc.v04n0507

Uses of Newer Anticonvulsants: An Update

Timothy R Berigan 1
PMCID: PMC327138  PMID: 15014710

Sir: Since the publication of a recent review of the psychiatric uses of newer anticonvulsants in the Companion,1 2 new anticonvulsants have come to market. The first is levetiracetam, which is U.S. Food and Drug Administration–approved as an adjunctive agent in treating partial-onset seizures in adults with epilepsy.2 Its precise mechanism of action is not known, but does not appear to be due to any interaction with known mechanisms involved in inhibitory or excitatory neurotransmission.3 Levetiracetam possesses a unique pharmacologic profile, a high margin of safety, and potential antiepileptogenic properties by potent inhibition of kindling.4 The principal route of elimination is renal, with about 66% of a dose excreted unchanged.5 To date, there are no published data on levetiracetam and bipolar disorder. However, 2 pilot studies on the treatment of bipolar disorder with levetiracetam are ongoing.6,7 There is 1 case report on the use of levetiracetam as monotherapy in acute mania in a patient who had failed more conventional mood stabilizers.8

The second new agent is zonisamide, approved as an add-on agent for partial seizures in adults.9 It appears to have several mechanisms of action, including blockade of voltage-sensitive sodium channels and T-type calcium currents, modulation of dopaminergic and GABAergic systems, and free-radical scavengers.10 The drug, which has been used in Japan for over 11 years as an anticonvulsant, is metabolized through the liver, is a mild liver enzyme inducer, and is titrated slowly.11 Because zonisamide has been used in Japan since 1989,10 most of the published data describing psychiatric uses are in Japanese without translation.12–14 To date, there is 1 open-label add-on study in English examining zonisamide as an adjunct in 24 patients with mania (15 diagnosed with bipolar mania; 6, with schizoaffective manic state; and 3, with schizophrenic excitement).15 Eighty percent of the bipolar patients, 66% of the schizoaffective patients, and 50% of the schizophrenic patients showed a moderate to remarkable improvement by the end of the fourth or fifth week.15 Kanba and Yagi16 earlier studied zonisamide in 6 patients with acute mania; 2 patients responded very well to zonisamide monotherapy, 1 patient with rapid cycling experienced a decrease in the severity of the episode, 1 schizoaffective patient stabilized, 1 schizoaffective patient progressed from hypomania to moderate depression, and 1 patient with mania did not respond to treatment. More data obtained in a controlled fashion will be required to determine if these new agents will prove to be of value in treating psychiatric disorders.

Footnotes

Dr. Berigan reports no financial affiliation or other relationship relevant to the subject matter of this letter.

References

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