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 (where one cannot “push” the dose due to risk of increasing side effects — nausea, diarrhea, or tremor with lithium; weight gain with valproate).
Because carbamazepine is so little understood, I made a brief video presentation about it, 5 minutes.
- 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
- 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 (except that virtually any medication you take can cause a rare “idiosyncratic” reaction, like an allergic response, and be fatal; this is more common for routine antibiotics than it is for routine mood stabilizers). 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 (a big hassle, but one way to make the immediate release form workable generics unless forced to by cost factors or the need for tiny dose increments. In the U.S., Carbatrol may be superior to Tegretol XR; the manufacturer emphasizes smoother blood levels over time (less “peaks and troughs”).
I usually begin with 200mg slow release twice daily, or even once daily if I’m really being cautious. I increase to 600 mg total 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. This 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 again 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 generally reduces the blood levels of almost any medication metabolized in the liver (most medications are). Thus carbamazepine has multiple potential interactions with other common medications, but generally it lowers 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, so-called “autoinduction”: blood levels of the medication 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 as though the medication “stopped working”, with this medication the dose must be increased just to maintain 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 saturates (re: enzyme induction) 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. Rather, I suggest following the “get to 1200” plan, unless you have side effects that will not diminish; in that case, you have reached your maximum dose, regardless of level.
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. Monitoring for blood cell problems is required, at least in the first 6 months. The manufacturer’s guidelines suggest monitoring beyond that point. Your doctor will help you decide how often to monitor.
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