Carbamazepine & Oxcarbazepine

Carbamazepine — Tegretol — was for a long time a first-line mood stabilizer alongside lithium and valproate. It is still effective, but it has been pushed into a narrower clinical role by two problems: drug interactions and a specific pharmacogenomic concern. Both are worth understanding because they teach you about CYP induction and pharmacogenomics in ways nothing else does.

The mechanism is voltage-gated sodium channel blockade, similar in concept to lamotrigine. The clinical effect — useful for bipolar mania, also useful for seizure disorders, also FDA-approved for trigeminal neuralgia — is broad.

The drug interaction problem is that carbamazepine is a potent inducer of CYP3A4, and to a lesser extent other CYP enzymes. That induction means carbamazepine accelerates the metabolism of many co-administered drugs. Oral contraceptives become less effective — pregnancies have occurred in patients who didn't know to switch contraception methods. Warfarin levels drop. Many psychotropics — including some antipsychotics, some antidepressants, and other mood stabilizers like lamotrigine — are cleared faster. The patient on carbamazepine needs every co-medication reviewed for induction effects, and contraception counseling is essential in women of childbearing potential.

Carbamazepine also induces its own metabolism — autoinduction. Over the first three to six weeks of treatment, plasma levels drop even at unchanged doses. The dose that achieved a therapeutic level at week one will not maintain that level at week six. Re-check the level after the autoinduction stabilizes (typically four to six weeks) and adjust dose accordingly.

The pharmacogenomic concern is HLA-B*1502. This allele is substantially more common in Han Chinese, Thai, Filipino, and some Southeast Asian populations. Carriers have approximately ten-fold elevated risk of Stevens-Johnson syndrome or toxic epidermal necrolysis with carbamazepine. The FDA recommends HLA-B*1502 genotyping before initiating carbamazepine in patients of Asian ancestry. Positive result means use a different agent. This is one of the cleanest examples of pharmacogenomic testing producing actionable clinical change.

Other monitoring: CBC for aplastic anemia (rare but real), LFTs for hepatotoxicity, sodium for hyponatremia, carbamazepine level. Therapeutic levels are typically 4-12 micrograms per milliliter.

Oxcarbazepine — Trileptal — is the structural cousin to carbamazepine designed to reduce some of these problems. Less potent CYP3A4 induction, no autoinduction, fewer drug interactions. The trade-off is more hyponatremia via SIADH — clinically significant in elderly patients particularly. Monitor sodium periodically. The HLA-B*1502 concern applies to oxcarbazepine as well in Asian populations.

For most bipolar patients today, carbamazepine and oxcarbazepine are not first-line. Lithium, valproate, lamotrigine, and the atypical antipsychotics with bipolar indications dominate practice. The patient who has done well on carbamazepine historically can continue, with careful drug interaction management. New starts usually go elsewhere.