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Chapter 37. Carbamazepine and Oxcarbazepine

Terence A. Ketter, M.D.; Po W. Wang, M.D.; Robert M. Post, M.D.
DOI: 10.1176/appi.books.9781585623860.419522

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Excerpt

Pharmacotherapy of bipolar disorder is a complex and rapidly evolving field. The development of new treatments has helped to refine concepts of illness subtypes and generated important new management options. Although the mood stabilizers—the first-line agents lithium, valproate, and lamotrigine and the alternative agents carbamazepine (CBZ) and oxcarbazepine (OXC)—are considered the primary medications for bipolar disorder, antipsychotics, antidepressants, anxiolytics, and a new generation of anticonvulsants are commonly combined with mood stabilizers in clinical settings (American Psychiatric Association 2002; Ketter 2005; Suppes et al. 2005). These diverse medications have varying pharmacodynamics, pharmacokinetics, drug–drug interactions, and adverse effects, thus offering not only new therapeutic opportunities but also a variety of new potential pitfalls.

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FIGURE 37–1. Carbamazepine and oxcarbazepine metabolism.CBZ = carbamazepine; CBZ-D = carbamazepine-10,11-dihydro-dihydroxide; CBZ-E = carbamazepine-10,11-epoxide; CYP3A3/4 = cytochrome P450 3A3/4 isoenzyme; MHD = monohydroxy derivative; OXC = oxcarbazepine.+ = indicates enzyme induction; – = indicates enzyme inhibition.

FIGURE 37–2. Stepped-care approach to bipolar depression.Composite schema of results from three different studies in which patients with bipolar depression received carbamazepine (CBZ) monotherapy (Post et al. 1986), lithium (Li) added to CBZ (Kramlinger and Post 1989b), and a monoamine oxidase inhibitor (MAOI) added to CBZ±Li (Ketter et al. 1995b). Each successive intervention yielded additional efficacy.
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TABLE 37–1. Carbamazepine (CBZ) and oxcarbazepine (OXC) in acute mania: 23 double-blind studies
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TABLE 37–2. Carbamazepine (CBZ) in acute depression: four controlled studies
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TABLE 37–3. Carbamazepine (CBZ) and oxcarbazepine (OXC) in prophylaxis of bipolar disorder: 16 controlled or quasi-controlled studies
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TABLE 37–4. Drugs whose serum concentrations are DECREASED by carbamazepine (and oxcarbazepine)
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TABLE 37–5. Drugs that INCREASE serum concentrations of carbamazepine (but not oxcarbazepine)

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CME Activity

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Sample questions:
1.
The main metabolic pathway of carbamazepine is mediated primarily through which of the following cytochrome P450 (CYP) enzyme systems?
2.
What is the major difference in oxcarbazepine’s metabolism in comparison with carbamazepine’s metabolism?
3.
Recent research has found that the risk of developing a serious rash with carbamazepine may be much higher in certain populations. Which patient population should be genetically tested before starting carbamazepine?
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