(revised 2/2019)

Carbamazepine can be a very effective mood stabilizer. You may not hear about it so much, because it is trickier to use and has some risks. The big risks are rare, but they sound scary. However, many people who use it get improvements in sleep and anxiety that could not be achieved with lithium or valproate.

Because carbamazepine is so little understood, I made a brief video presentation about it, 5 minutes; but the same stuff and more is covered below.

Advantages:

  • no weight gain (generally no more than our society commonly produces)
  • no side effects for most people once they are up to speed
  • often significant help with sleep

Disadvantages:

  • Rare risks to blood, skin, liver
  • Interacts with many other medications
  • Decreases the reliability of birth control pills, requiring condoms or an IUD
  • Requires multiple blood test follow-ups

In general, we probably don’t use it often enough, getting scared away by the risks. However, there is a growing concern that it can cause decreased bone density, although that has not been fully established yet. But between this and the interference with birth control pills, it makes it hard to use for young women. Nevertheless, the risks that go with getting manic symptoms are substantial; and some young women cannot tolerate lithium. And most young women should not use divalproex because of its tendency to cause “polycystic ovarian syndrome”. So sometimes, one has to consider carbamazepine despite the risks.

Carbamazepine can rarely cause a severe anemia — your bone marrow stops making red blood cells. Less rarely, though still very uncommonly, it can cause the marrow to stop making white blood cells. These are your infection-fighting cells, and without enough, you would be vulnerable to a severe infection. Unfortunately, you cannot feel your white blood cell level (too few red cells — “anemia” — is a problem you can feel!). Therefore blood tests are required at least for the first 6 months when this white cell problem usually shows up; after that, it’s much less clear when or even if to monitor; here’s a little essay on balancing tests and safety.

While lithium and valproate may have more daily side effect risks, at least they do not have these potentially fatal risks (though virtually any medication you take can cause a rare “idiosyncratic” reaction, like an allergic response, and be fatal). Thus for almost all patients, carbamazepine is a distant second choice relative to lithium and valproate.

Slow release formulas can make a difference in tolerability: if you cannot tolerated the immediate release 100 or 200 mg , even if you split the dose to 3 times a day ( which is a hassle, but one way to make the immediate release form workable.)

I usually begin with 100mg twice daily, or even once nightly if I’m really being cautious. I increase to 600 mg total (e.g. 300 mg twice daily) as soon as the lower dose is clearly tolerated. Some patients just can’t take carbamazepine even in the lowest doses: they develop severe nausea, dizziness, and a listlessness that does not diminish with time. That makes things a little tricky, as these are the side effects (along with blurred vision) of too high a carbamazepine level. However, patients who can handle the lower doses will generally find these side effects diminish rapidly, within 3-4 days. They often experience them at each dose increment, again diminishing quite rapidly.

Carbamazepine increases the activity of enzyme systems in the liver, so that the liver chews up medications more quickly. This reduces the blood levels of other medications you might be taking (not all, but most). Thus carbamazepine has potential interactions with other common medications, generally lowering their levels. So the risk to watch for is loss of effectiveness of a medication that was previously working. There are two classic medications to watch for in this respect: warfarin (coumadin), a blood thinner; and birth control pills! Women on BCP’s are at risk of pregnancy when carbamazepine is started and should use additional means of birth control until their cycles are clearly regulated and the dose of carbamazepine is no longer increasing.

This enzyme increase also affects carbamazepine itself: blood levels of carbamazepine fall as the induction (enzyme increase) occurs, generally over the first three months on the medication. It is crucial to recognize that although you may feel the medication “stopped working”, it may be that all you have to do is turn up the dose to get back to the original, effective blood level.

At one conference I heard someone advocate “get to 1200 mg”, and since following that suggestion I have had more success with this medication. It is as though everyone’s liver eventually becomes similar in enzyme activity at this dose.  Blood levels on 1200 mg are usually at the top of the therapeutic range. However, levels do not predict response well, so there is usually little reason to measure them. So I generally follow the “get to 1200” plan. Just keep increasing, slowly, until it’s working fully — unless there are side effects that will not diminish.  In that case, go back down one step until those side effects are gone or fully manageable, and that’s the maximum dose. See how blood levels don’t really matter?

Rash is common with carbamazepine and can progress to a severe skin condition called “Stevens-Johnson Syndrome”, which can be fatal. You must watch for a rash, call if in doubt, and you may have to stop the medication if a rash occurs.

When does the rash show up, if it’s going to?

(Update 5/2015): For almost everyone who’s going to react to carbamazepine with a rash, it happens in the first three weeks, and the majority get it in two weeks. After that, the risk is far, far lower (but not zero, so don’t entirely relax vigilance). Levi

CBZ rash onset graph