Trileptal

TRILEPTAL

Trileptal (oxcarbazepine) is currently FDA-approved only for use in treating certain types of seizure disorders. However, for many years, this drug has been used in Europe as a mood-stabilizer for patients with bipolar disorder.

Trileptal and Tegretol 
(oxcarbazepine and carbamazepine)

Trileptal is not really a "new" medication.  It's just an old one, carbamazepine (Tegretol) with an oxygen stuck on it.  But fortunately this oxygen solves the biggest problem that kept carbamazepine a very distant third choice compared to lithium and Depakote -- the tendency to decrease white blood cells, which are your infection-fighting cells.  Since people don't "feel" their white blood cells, these could get dangerously low and leave a person vulnerable to infection.  Tegretol is still a reasonable choice.  It's still around as a choice because as generic carbamazepine it's quite a bit cheaper than Trileptal. 

The difference with Trileptal is that it does not cause the blood cell problem.  The medication has been in use in Europe for 10 years, and that's how the manufacturer has learned this.  How do you know if they are right?  Here's why:  if the manufacturer says it's not a problem, and they're wrong, they could get sued and would very likely lose millions of dollars.  So they do not make these claims lightly.  Compare Tegretol: there are warnings all over the paperwork that comes with that medication, from the manufacturer, to make sure no one forgets to caution patients about this problem. 

Trileptal also seems to cause side effects less often than Tegretol.  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.   

A few of my patients so far have had to stop Trileptal 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 Trileptal (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 Trileptal 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 Tegretol, and Trileptal seems to act like that medication in almost all respects.  But I've not seen people gain weight on Tegretol, 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 Depakote, or less so, lithium.  So far Trileptal seems, like Tegretol, to be neutral as far as weight gain risk goes. 

But does it work?!  Yes; it seems to be very similar to Tegretol in that respect.  It does not work for everyone, which is of course the same story as for any of these mood stabilizers -- for any given person, sometimes one will work and another not at all.  Tegretol has not been as well studied as Depakote, and particularly lithium, for which we have the best research.  But most studies show Tegretol in the same general league as Depakote in terms of effectiveness, which has certainly been my experience with it as well.  And so far, Trileptal has been about as good as Tegretol, perhaps just a bit less so.  I don't have many patients who've done well on Trileptal alone, compared to a few folks who have, on Tegretol alone.  

There are few studies of the effectiveness of Trileptal.  The randomized/blinded trials are small and old.  There is a recent chart review study showing moderate effectiveness.^Ghaemi     There is a great review of all the Trileptal data available up to 2002 through Bipolar Network News. 

Thus it appears that at this point, with 10 years of European experience and now some here in the U.S., Trileptal has some advantages over other mood stabilizers: 

• low potential for risky side effects;
• few side effects at all, in most people (though that is true of lithium and Depakote at low doses);
• does not require blood tests before or during its use;
• can be started quicker than lamotrigine;
• does not appear to be associated with weight gain like Depakote (or less so lithium);
• less likely than lithium to produce bothersome side effects. 

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: Trileptal may have a place among the "first-line" treatments for bipolar disorder.  Particularly if weight gain is a highly feared risk, and depression is not prominent -- see last paragraph above -- I would support a patient's decision to start with Trileptal.