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Carbamazepine 
(U.S.: "Tegretol XR", "Carbatrol")

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.  This is why Trileptal, which is carbamazepine with an extra oxygen (oxcarbazepine) is an important new medication: it does not cause this blood cell problem -- but it's much more expensive than carbamazepine, which is available as a generic.

However, when forced to use it by side effects or insufficient response to valproate and lithium or money-limits, carbamazepine can be an extremely effective mood stabilizer. Most people can handle doses pushed to the usual maximum, 1200 mg,  over time.  Most 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, tremor or worse with lithium; weight gain with valproate).

Slow release formulas make a very big difference in tolerability: do not use 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, with the "autoinduction" phenomenon reviewed below, 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. 

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