Oxcarbazepine in the Treatment of Bipolar Disorder: A Review

Article excerpt

Objective: To review the data on the efficacy of oxcarbazepine (OXC) in bipolar disorder (BD) and to provide recommendations for clinicians on the use of this medication in treating BD.

Method: Using the terms oxcarbazepine and bipolar disorder, oxcarbazepine and mania, or oxcarbazepine and bipolar depression, we conducted a computer-aided search of MEDLINE for the years 1950 to 2005.

Results: Case reports, retrospective chart reviews, open prospective studies, and double-blind studies reported the efficacy and effectiveness of OXC in treating BD. The data indicate that OXC has efficacy in treating acute mania and may be a useful add-on in treating acute bipolar depression and in BD prophylaxis. OXC is generally well-tolerated.

Conclusion: We recommend using OXC as monotherapy or as add-on therapy in refractory mania, but we recommend it be used predominantly as an add-on treatment for other phases of BD in patients who have not improved with well-established treatments or in patients who have difficulty tolerating adequate dosages.

(Can J Psychiatry 2006;51:540-545)

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Clinical Implications

* OXC is effective in treating acute mania.

* OXC can be used as an adjunctive treatment for refractory BD.

* Compared with carbamazepine, OXC has fewer drug interactions and is better tolerated.

Limitations

* The efficacy of OXC in bipolar depression has not been widely studied.

* It is unknown whether OXC has efficacy in the maintenance treatment of BD.

* Although it is recommended for use in refractory BD. the data suggesting this strategy are not supported by Level I evidence.

Key Words: oxcarbazepine, bipolar disorder, mania, depression, drug interactions

Abbreviations used in this article

BD bipolar disorder

BRMRS Bech and Rafelson Mania Rating Scale

CARS-M Clinician Administered Rating Scale for Mania

CBZ carbamazepine

CYP cytochrome P450

DHD dihydroxy metabolite

IMPS Inpatient Multidimensional Psychiatric Scale

MHD monohydroxy metabolite

OXC oxcarbazepine

SD standard deviation

VPA valproate

YMRS Young Mania Rating Scale

Although lithium is considered the gold standard of treatment for BD, research and clinical experience over the past 4 decades have indicated that only a small proportion of patients with BD remain episode- or symptom-free using lithium monotherapy in long-term maintenance treatment (1,2). Thus, to improve outcomes for a substantial number of patients with BD, anticonvulsants and atypical antipsychotics are often used as alternatives or augmentation strategies to lithium. Among anticonvulsants, VPA and CBZ have proven efficacy in treating acute mania (3), and they are likely effective in maintenance treatment, although well-designed double-blind, placebo-controlled trials supporting their prophylactic efficacy are lacking. Although VPA is generally well tolerated, CBZ has significant side effects. Further, it induces CYP enzymes leading to numerous drug interactions with concomitant medications.

OXC is an anticonvulsant developed through structural variation of CBZ with the intention of avoiding metabolites that cause side effects. OXC is metabolized primarily through its reduction to an MHD form that undergoes glucorinidation. OXC is better tolerated than CBZ because it has fewer side effects. Owing to its better tolerability profile, OXC is used increasingly to treat BD.

This paper systematically reviews the pharmacology of OXC and the data on its efficacy in treating BD and provides recommendations for clinicians on the use of this medication in treating BD.

Method

Using the terms oxcarbazepine and bipolar disorder, oxcarbazepine and mania, or oxcarbazepine and bipolar depression, we conducted a computer-aided MEDLlNE search for the years 1950 to 2005 . …