Oxcarbazepine (Trileptal)

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Oxcarbazepine is a very appealing alternative to carbamazepine except for one thing — it doesn’t work anywhere near as well.

When I first wrote this page 10 years ago, oxcarbazepine looks like a promising alternative. We had been using carbamazepine for years, and there were some significant well-known problems with it. It looked like maybe oxcarbazepine would relieve us of some of those problems.

Unfortunately, in the last 10 years, I have come to recognize that none of my patients have done well enough on oxcarbazepine to take it alone, with nothing else. I have switched lots of patient’s from oxcarbazepine to carbamazepine and seen them do much better. So I have stopped using oxcarbazepine at all.

Oxcarbazepine does have the advantage of not requiring blood tests. This makes it attractive in child/adolescent psychiatry, where the clients are not very fond of getting stuck with needles. Unfortunately, I think that in the name of avoiding lab testing, patients are given a medicine which is just not going to work as well.

With that introduction, here is what I wrote in 2003 with a few revisions to reflect this change of opinion about it.

Oxcarbazepine/Trileptal is not really a “new” medication. It’s just an old one, carbamazepine/Tegretol with an oxygen stuck on it. This oxygen solves a problem that kept carbamazepine a distant third choice compared to lithium and divalproex/Depakote:  the tendency to decrease white blood cells, which are your infection-fighting cells.

Oxcarbazepine also seems to cause side effects less often than carbamazepine. By going up slowly on the dose, people seem to be able avoid very the nausea and dizziness that are listed as side effects for this medication, nearly entirely. However, as the dose nears the top of what people can tolerate, dizziness and cognitive slowing/dulling are common. These usually are the limiting factors in how high we can push the dose. Few of my patients have been able to handle any more than 1800 mg, which is about 3/4 of the rated maximum dose (2400 mg); most people end up around 1200-1500 mg and even then they have some fuzziness. To avoid that most people have to stay at 1200 mg per day or less, and then it doesn’t work as well as it should (my opinion; you’ve figured out that I prefer carbamazepine?)

Some people have to stop oxcarbazepine for ankle swelling. That’s related to the known problem with hyponatremia — a lowering of blood sodium that occurs in about 3 people per 100 treated. For most people this feels like getting the ‘flu: generally a little ill, slowed down, weak, maybe a headache. This would be regarded as a “side effect”. Since I tell my patients to lower the dose for any side effect, this has not become a problem. The very worst thing I could find in the published literature on hyponatremia and oxcarbazepine (the manufacturer sent the existing data on this at my request) was a coma in a 70 year old who was also taking Depakote. When oxcarbazepine was stopped she came out of it with no lasting problems. For more, see a nice review of this hyponatremia issue from 1994.

What about weight gain, since many similar medications seem to cause this problem? “Weight gain” is listed for carbamazepine, and oxcarbazepine seems to act like carbamazepine in almost all respects. But I’ve not seen people gain weight on carbamazepine, and I’ve used a lot of it. If it does cause weight gain at all, it’s not even close to the league of divalproex. Overall oxcarbazepine seems, like carbamazepine, to be neutral as far as weight gain risk goes.

There are few studies of the effectiveness of oxcarbazepine. The randomized/blinded trials are small and old. There is a recent chart review study showing moderate effectiveness.Ghaemi (Update 2013: No significant research has emerged since then to support its use . . .)

The problem is, this medication may not have quite as much oomph” as the more widely tested medications like lithium, Depakote, and more recently lamotrigine and olanzapine. Worse yet, the manufacturer is not going for an “FDA indication” for bipolar disorder, so we are unlikely to see large head-to-head trials of this medication versus those more standard approaches. At this point it is mainly on the list because it causes so few problems and has so few long-term risks compared to the others.

Obviously that makes for a tricky decision: should you try a medication that may not have as much power as the others but is less likely to cause other problems? This medication may be for people whose symptoms are not severe; who do not need to see improvement right now; or who need to add something to an existing set of medications. It could be an appropriate starting place for someone has a lot of manic-side symptoms — sleep problems, irritability, agitation — but whose symptoms are not currently severe. By comparison, if the symptoms were more on the depressive side — low energy, low motivation, sleeping a lot, everything looks negative — lamotrigine appears from current data to be a better choice with similarly few side effects (but one bigger risk, the rash problem; see lamotrigine).

Conclusion: oxcarbazepine does not have a place among the “first-line” treatments for bipolar disorder. If you’re looking at it, most of the time you’d be better off considering carbamazepine.

(updated 11/2014)

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