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Evidence-based psychiatric medicine: Oxcarbazepine for acute mania.

The Problem

You have a patient with bipolar disorder. He is currently in an acute phase of mania without psychosis. For various reasons, he declines treatment with lithium, valproate, carba-mazepine, or antipsychotic medications. You consider treatment with oxcarbazepine.

The Question

Is oxcarbazepine effective for the treatment of acute mania?

The Analysis

We searched the Cochrane Database of Systematic Reviews (www.cochrane.org) and found no reviews. We then searched Medline, combining "oxcarbazepine or trileptal" and "bipolar or mania."

The Evidence

Oxcarbazepine was approved in 2000 for mono- or adjunctive therapy in the treatment of partial seizures in adults. Since its release as an antiepileptic drug, the published research evaluating the efficacy of oxcarbazepine in the treatment of bipolar disorder has been limited. Although the precise mechanism of action is unknown, oxcarbazepine does block voltage-sensitive sodium channels, resulting in the stabilization of neuronal membranes.

Our search strategy found a fairly recent Canadian review that included chart reviews, open prospective studies, and double-blind studies up to and including 2005 (Can. J. Psychiatry 2006;51:540-5). We were not able to locate any relevant studies published since this review.

Six case reports described the efficacy of oxcarbazepine (1,200-2,400 mg/day) as mono- or adjunctive therapy. Chart reviews of 628 patients with bipolar disorder showed that oxcarbazepine (300-3,000 mg/day) as mono- or adjunctive therapy yielded a response rate of 50%-100%. One of the studies included in the review retrospectively compared oxcarbazepine (n = 27) with valproate (n = 27) add-on therapy in patients with the depressive phase of bipolar disorder, schizoaffective disorder, or major depressive disorder. Efficacy was similar between the two groups.

Several open-label prospective studies have been done. One study compared oxcarbazepine 900mg/day combined with haloperi-dol (n = 10) with haloperidol only (n = 10) in the treatment of mania associated with bipolar or schizoaffective disorder. Although both groups improved, the dose of haloperidol required in the oxcarbazepine group was approximately half of that required in the haloperidol-only group (12.3 vs. 24.9 mg/day).

One study examined the efficacy of oxcarbazepine in an open, nonrandomized trial of 12 patients with mild to moderate mania. Initially, patients were treated with oxcarbazepine monotherapy for 14 days. A 7-day washout period was followed by reinitiation of oxcarbazepine 900-2,100 mg/day for another 14 days. At the end of the first phase, 25% of patients met criteria for response. At the end of the second phase, 33% of patients met criteria for response. Response was defined as a 50% reduction in the Young Mania Rating Scale.

Another group of investigators compared the efficacy of oxcarbazepine with valproate in a single-blind, active-comparator trial. In this study, 57 patients with mania who had received active treatment with valproate for at least 8 weeks were randomly assigned to continue treatment with valproate or to switch to oxcarbazepine. Of these patients, 23 who were switched to oxcarbazepine and 19 who continued valproate completed the 10-week study. Study dosages were 1,000-4,000 mg/day for valproate and 1,200-2,400 mg/day for oxcarbazepine. With the Clinician-Administered Rating Scale for Mania, no significant differences were found between the two groups.

In a small, double-blind, placebo-controlled study, five patients were treated with valproate (dosage not given) and six patients were treated with oxcarbazepine (1,800-2,100 mg/day). Oxcarbazepine performed significantly better than placebo and was comparable with valproate in efficacy. (The duration of each treatment phase varied and was unknown to doctors and patients. These results were published in the mid-1980s.)

Around the same time, the same researchers performed another double-blind study comparing the efficacy of oxcarbazepine with haloperidol and lithium. Oxcarbazepine (n = 19; mean dosage, 2,400 mg/day) had similar efficacy to haloperidol (n = 19; mean dosage, 42 mg/day). Oxcarbazepine (n = 26; mean dosage, 1,400 mg/day) had similar efficacy to lithium (n = 26, mean dosage, 1,100 mg/day). A different group of researchers performed a double-blind study comparing oxcarbazepine (900-1,200 mg/day) with haloperidol (15-20 mg/ day) in the treatment of acute mania in 20 randomly assigned patients. Efficacy was comparable in this study, which was also done in the mid-1980s, but the onset of action of oxcarbazepine was faster.

The Conclusion

The best available evidence suggests that oxcarbazepine is effective in treating acute mania, but one needs to remain mindful that treatment effects may have been overestimated in these small observational studies. Further-more, the double-blind studies were all done in the 1980s, prior to oxcarbazepine's approval for use in epilepsy, and study populations were small in size.

DR. LEARD-HANSSON is a forensic psychiatrist who practices in San Diego. DR. GUTTMACHER is chief of psychiatry at the Rochester (N.Y.) Psychiatric Center. They have no financial interest in any product or service discussed in this column. They can be reached at cpnews@elsevier.com.

BY JAN LEARDHANSSON, M.D.

BY LAURENCE GUTTMACHER, M.D.
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Article Details
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Title Annotation:Adult Psychiatry
Author:Leard-Hansson, Jan; Guttmacher, Laurence
Publication:Clinical Psychiatry News
Date:May 1, 2008
Words:816
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