Oxcarbazepine: Does It Have a Role in Bipolar Disorder?

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BIPOLAR UPDATE

Oxcarbazepine (formerly branded as Trileptal) is an anticonvulsant that is structurally very similar to carbamazepine, which is US Food and Drug Administration-approved for acute or mixed mania but not well studied for depression. Both are thought to work by the same mechanism(s). The drug came to market as an anticonvulsant with very little time left on its patent protection, and it very quickly became a generic product. There was not enough time to do any significant studies on other possible uses such as in bipolar disorder before the patent ran out. Hence, there are very little data pertinent to its efficacy or effectiveness for bipolar mania or depression. What data are available are at best inconclusive,¹ but Maudsley Prescribing in Psychiatry, citing 8 pertinent reports, rate it as “probably effective” for mania—the only medication with that rating in a table of 13 off-label possible alternative treatments.²

The only placebo-controlled study was in children and adolescents.³ The study included a total of 116 patients with symptoms of mania aged 7 to 18 years who were randomized to oxcarbazepine or placebo. There was no significant difference on the Young Mania Rating Scale, nor on rate of response defined as a 50% improvement in the scores. However, the response rates were 42% with oxcarbazepine and 26% with placebo, which looks like it could have become a significant difference if the cohort had been larger.

Oxcarbazepine has a somewhat milder adverse effect profile compared with carbamazepine. Probably the most significant risk with oxcarbazepine is hyponatremia; this most often occurs in the first 3 months of use, but it can occur later. Although few head-to-head comparisons are available,² the incidence might be higher in oxcarbazepine than with carbamazepine. The overall rate is about 2% to 3%, but concomitant selective serotonin reuptake inhibitors (which can lower sodium by a different mechanism) probably increase this risk. Sodium monitoring should occur monthly for the first 3 months and every 3 to 6 months thereafter.

Adverse effects that appear less often with oxcarbazepine include liver enzyme elevations (it is not metabolized and is renally excreted), serious rashes including Stevens-Johnson syndrome, leucopenia, sedation, and other rashes. It is a weaker inducer of cytochrome P450 3A4 compared with carbamazepine and thus has fewer drug interactions. Both oxcarbazepine and carbamazepine are weight-neutral, but they can cause double vision and vertigo. Slower titration may minimize these and other adverse effects. Teratogenicity is a severe problem with carbamazepine; the incidence is unclear with oxcarbazepine but it probably should be considered to be an equally high risk in women of child-bearing potential.

Dosage of oxcarbazepine is about one-third higher than with carbamazepine. The same dose has been used for bipolar mania as is used for seizure disorders; begin with 300 mg bid and increase every 3 days by 300 mg to the maximum dose of 2400 mg, if needed and tolerated. Serum levels are not available.

In conclusion, it seems that oxcarbazepine could be a consideration for patients who you want to treat with carbamazepine for mania (as monotherapy or adjunct) but for whom it would be unsafe or who have been unable to tolerate it. It is unlikely to be of value for someone who had an adequate trial of carbamazepine and has not responded. The evidence base for treating or preventing bipolar depression is very weak for both.

Dr Osser is associate professor of psychiatry, Harvard Medical School, and Consulting Psychiatrist, US Department of Veterans Affairs, National Telemental Health Center, Bipolar Disorders Telehealth Program, Brockton, MA. He is a member of Psychiatric Times® Editorial Board. The author reports no conflicts of interest concerning the subject matter of this article.

References

1. Vasudev A, Macritchie K, Vasudev K, et al. Oxcarbazepine for acute affective episodes in bipolar disorder. Cochrane Database Syst Rev. 2011;(12):CD004857.

2. Taylor DM, Barnes TRE, Young AH. The Maudsley Prescribing Guidelines in Psychiatry, 13th Edition. Hoboken, NJ: Wiley Blackwell; 2018: 237.

3. Wagner KD, Kowatch RA, Emslie GJ,et al. A double-blind, randomized, placebo-controlled trial of oxcarbazepine in the treatment of bipolar disorder in children and adolescents. Am J Psychiatry. 2006;163:1179-1186.❒