Bipolar Disorder Medication Spotlight: Tegretol (Carbamazepine)

By Candida Fink MD

With this post, we continue our biweekly series on medications used to treat bipolar disorder and related symptoms. This week, we focus the spotlight on Tegretol (carbamazepine) – an anti-seizure medication that has been found useful in treating bipolar disorder. Following are some of the primary benefits Tegretol offers:

• Useful in treating acute mania and mixed states particularly when a person doesn’t respond well to or tolerate lithium or valproate (Depakote).
• May also help with maintenance treatment – reducing the frequency of all cycles.
• Does not typically cause significant weight gain in most people who take it.

Although most people tolerate Tegretol, it does have some drawbacks and negative side effects, including the following:

• Can reduce effectiveness of birth control pills.
• Has potentially serious interactions with a number of other medications.
• May lead to reduction of white blood cells or platelets. Your doctor will want to run blood tests before beginning treatment and regularly thereafter to monitor your white blood cell and platelet counts and the concentration of Tegretol in your blood.
• Could cause or contribute to liver problems. Again, your doctor may order liver function tests before starting carbamazepine and then about every six months to rule out any problems.
• Blurred vision.
• Difficulty with balance and walking called ataxia.
• Nausea.
• Severe skin reaction called Stevens Johnson Syndrome.

The possibility of the severe skin reaction from Tegretol has always been known. However, recently it has been discovered that people of Asian ancestry who carry a specific genetic marker are at particularly high risk of a dangerous skin reaction from Tegretol. This means that if a physician wishes to prescribe Tegretol to a person of Asian ancestry, they will need to get a test for this marker which is called HLAB*1502. The test is already commonly used in transplant patients and is readily available. The marker is not a genetic abnormality but rather just one of many possible variations. This variant is found almost exclusively in individuals of Asian ancestry. The skin reaction can happen in other people without the marker, so monitoring for skin reactions is still important regardless of ancestry.

Tegretol is used far less often than Depakote – for no particular reason it seems other than habit on the part of physicians. It is a good medication with a generally well tolerated side-effect profile, but it does require frequent blood tests and can be difficult to use in people who take a number of different medications. While Tegretol may be used alone to treat bipolar mania and cycling, it is also used (and possibly more often) as an additional agent – layered on to something like lithium or Depakote.

Unlike lithium and Depakote, there seems to be no set blood level (concentration of Tegretol in the blood) that is considered therapeutic (effective in preventing mood cycling). But there are levels in the blood that can be too high, so blood levels are still drawn regularly. To prevent negative side effects from occurring, your doctor is likely to start you at a low dose and ramp up the dosage slowly until symptoms appear in control.

Tegretol has the unusual property of causing its own blood level to drop as the doses are increased. Tegretol pumps up the activity level of the very enzymes that break it down, so frequent blood level checks are necessary at the beginning of treatment until the enzymes are maximally “induced” in this way.

Another anti-seizure medication is available that’s actually one of the breakdown products of Tegretol – called Trileptal (oxcarbamazepine) – that does not require such regular blood levels and does not have some of the other potential risks of carbamazepine. Physicians have begun prescribing it to treat bipolar disorder, but there is really no data to support its use. One study was done in children and adolescents, which showed the medication was no better than placebo. Adult research is almost nonexistent. Trileptal carries a risk of lowering sodium concentration in the blood, so sodium levels must be monitored if someone is taking Trileptal.

Caution:Tegretol comes with several warnings, including the following:

• Never stop taking any medication cold turkey, especially an anti-seizure medication. Withdrawing an anti-seizure medication too quickly can actually cause seizures. Always consult your doctor before you stop or decrease your medication.
• Grapefruit and grapefruit juice tend to increase the concentration of Tegretol in your system, so avoid it if you’re taking this medicine.
• Because Tegretol can decrease the effectiveness of contraceptive pills, be sure to tell your doctor if you’re taking the pill to prevent pregnancy. Also let your doctor know if you’re trying to become pregnant.
• Be sure to tell your doctor if you are taking or about to start taking any other medications, herbals, vitamins, or over the counter products because many substances can affect levels of Tegretol in the blood.

If you’ve taken Tegretol for bipolar disorder or are a doctor who has prescribed it, please share your experiences, insights, and observations.

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