Oxcarbazepine treatment of refractory bipolar illness.

To the Editor: Numerous studies over the past 25 years have demonstrated the efficacy of carbamazepine in bipolar illness. (1) Unfortunately, carbamazepine can be a difficult medication to use, due to significant drug-drug interactions, laborious titration related to enzyme autoinduction (both due to induction of the cytochrome P450 system), potential for agranulocytosis and hyponatremia.

Oxcarbazepine, the 10-ketoanalog of carbamazepine, is an effective anticonvulsant and shows little interaction with the cytochrome P450 system and minimal risk of agranulocytosis. (2) Surprisingly, there are only a few reports of its utility in bipolar illness. We present such a case.

A 62-year-old man with a 40-year history of bipolar illness had become quite refractory to treatment, with recurrent severe manic and depressive episodes. He ultimately responded partially to a combination of lithium and valproic acid; clozapine 75 mg b.i.d. was added, resulting in complete remission of all symptoms.

He remained symptom-free for the subsequent 26 months, but then developed critical agranulocytosis. Risperidone was substituted for clozapine with rapid normalization of the white count, but he became manic and was hospitalized.

On the inpatient unit, the patient was pressured, tangential, intrusive and grandiose, sleeping less than one hour per day. Despite numerous medication trials, the patient's manic symptoms continued to worsen, with worsening pressured speech to the point of incoherence, echolalia and impulsive screaming. Young Mania Rating Scale (YMRS) score at that point was 28.

We considered introducing carbamazepine, but as the patient was on warfarin for a history of pulmonary embolus, we instead added oxcarbazepine, which was titrated to an ultimate dose of 600 mg b.i.d. He tolerated this well, with no side effects. The addition of oxcarbazepine proved dramatically effective, with rapid resolution of all manic symptoms; within two weeks, YMRS was 3. The patient remains on lithium carbonate 900 mg q.h.s. (serum level 0.9 mEq/L) and oxcarbazepine 600 mg b.i.d., and his symptoms have remained in remission for the past four months.

Given its structural and pharmacologic similarity to carbamazepine and its clinical advantages, it is surprising that oxcarbazepine has not been studied more extensively in bipolar illness. There were only a few small, controlled studies in Europe in the 1980s (3-5) and only case reports and small uncontrolled series since. (1) Oxcarbazepine is better tolerated and simpler to use than carbamazepine, and this limited, but positive, experience warrants more extensive controlled trials.

Tricia G. Majczenko, MD

Department of Psychiatry

Jonathan T. Stewart, MD

Geropsychiatry Section

University of South Florida College of Medicine 

Bay Pines VA Medical Center

Bay Pines, FL

References

1. Hirschfeld RMA, Kasper S. A review of the evidence for carbamazepine and oxcarbazepine in the treatment of bipolar disorder. Int J Neuropsychopharmacol 2004;7:507-522.

2. Bazil CW. Antiseizure drugs. In Noseworthy JH (ed). Neurological Therapeutics: Principles and Practice. London, Martin Dunitz, 2003; pp. 297-307.

3. Emrich HM, Altmann H, Dose M, et al. Therapeutic effects of GABA-ergic drugs in affective disorders: a preliminary report. Pharmacol Biochem Behav 1983;19:369-372.

4. Emrich HM, Dose M, von Zerssen D. The use of sodium valproate, carbamazepine and oxcarbazepine in patients with affective disorders. J Affect Disord 1985;8:243-250.

5. Emrich HM. Studies with (Trileptal) oxcarbazepine in acute mania. Int Clin Psychopharmacol 1990;5:83-88.