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Oxcarbazepine: An Alternative to Carbamazepine
I. What is Oxcarbazepine (OXC)?
Oxcarbazepine (Trileptal®) is similar to the better-known anticonvulsant, carbamazepine (CBZ, Tegretol®). OXC has been approved as an anticonvulsant in Europe since the early 1980s; it was approved in the United States in 2000 for use as monotherapy in partial seizures in adults, and as adjunctive therapy in children ages 4-16 for partial and secondary generalized seizures. OXC is the 10-keto analogue of CBZ, meaning it is structurally similar to, but differs slightly from, the chemical structure of carbamazepine. The main active metabolite of OXC is the monohydroxy derivative (MHD). In contrast to CBZ and its active epoxide metabolite, OXC and its MHD have fewer side effects and negative drug interactions. For this reason, and given CBZ’s proven effectiveness in bipolar disorder, OXC has recently been further studied as a possible mood stabilizer, with the added advantage of fewer serious side effects than CBZ.
II. How Effective is OXC as a Mood Stabilizer?
OXC was first used as a mood stabilizer in bipolar disorder in 1983, when Dr. Hinderk Emrich of the Max Planck Institute in Munich, Germany, studied 6 patients with manic psychoses in a double-blind, on (OXC)–off (placebo)–on (OXC) trial design.1 In this study, manic symptoms were reduced by 50% in patients during the OXC trials, compared with only 26% on placebo. High doses of OXC were used in this study (1800-2100 mg/day), and no major side effects were reported. To date, in 18 other open-label studies or case reports of OXC in bipolar disorders, the majority show mild to moderate improvement on OXC with few significant side effects (Click here to see table). Dr. Emrich’s further studies of OXC in 1990 showed that for patients with acute mania, OXC was equally effective as haloperidol or as lithium in reducing manic symptoms in two separate randomized two-week studies.2
In a recently published study, Hummel et al.3 found that with OXC monotherapy for acute mania, one third of the patients improved during an on-off-on study of OXC versus placebo for 35 days. Those patients with moderate mania improved the most. However, in contrast to observations with CBZ, those patients with severe or psychotic mania did not respond to OXC at all.
1 Emrich HM, Altmann H, Dose M, and von Zerssen D (1983). Therapeutic effects of GABA-ergic drugs in affective disorders - A preliminary report. Pharmacol Biochem Behav 19: 369-372.
2 Emrich HM (1990). Studies with oxcarbazepine (Trileptal) in acute mania. Int Clin Psychopharmacol 5: 83-88.
3 Hummel B, Walden J, Stampfer R, Dittmann S, Amann B, Sterr A, Schaefer M, Frye MA, and Grunze H (2002). Acute antimanic efficacy and safety of oxcarbazepine in an open trial with an on-off-on design. Bipolar Disord 4: 412-417.
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