Q:  Asian Heritage & Med Sensitivity?

Dr. Phelps,

You mention you have extremely medication sensitive patients.  My 19-year old daughter is the most hyper sensitive patient her doctor has ever treated.  She is bipolar II with mixed episodes.

Question:  Does that mean that she may respond to meds faster than normal?  She became manic in 3 days after she started taking 1/4 of a .75 Wellbutrin pill (this was added to her cocktail of 1/2 ml of Prozac and 225 mg of Trileptal, both of which she had taken for a long time).  So we quit both the Wellbutrin and Prozac immediately and added 40 mg of lithium.  It "kicked in" by the third day.  Unfortunately, we had to quit because she became severely depressed 3 weeks after stopping the antidepressants. (I guess it took that long to get "cleared out" of her system).  To combat the depression, her pdoc added the Prozac back in and she "perked up" the next day.  But 4 days later, she is experiencing racing thoughts and agitation again (manic?)

She is Japanese and I know that Asians are often more sensitive to meds.  Have you heard of a mood stabilizer that works "best for Asians?" (is there such a thing?)  

I'm wondering if maybe she needs to be back on lithium at a lower dose?  Or maybe lower the Prozac?  She has always had an underlying stress/anxiety disorder.  

What would you recommend?  Thank you for your insight!


Dear Ms. M' -- 
Sorry to hear about what you've been through.  Some thoughts:  first, lithium can indeed "kick in" within 3-4 days, in fact that's precisely when I start looking for some impact (although the full effects might not develop for a month or so, and there is reason to think that something would still be changing the better even many months later). So that particular medication effect may not be part of your daughter's story, although that dose, at 40 mg, is very small indeed, so that does match your sense that small doses of things do a lot. . I

As you may have learned,  lithium is handled in the body very differently than most other medications: it goes out through the kidneys without having been changed ("metabolized") by the liver.  By contrast, liver metabolism is the route by which most medications are inactivated and removed from the body (ultimately the breakdown products go out in stool or urine). There are a group of liver enzymes which are responsible for most medication metabolism. These are called the cytochrome P-450 enzymes.  There are about six which metabolize most medications.  

One enzyme, 2A6, is responsible for metabolizing nicotine from cigarettes. Few Europeans have the slow version of this enzyme, but 15-20% of Asians do.  A possible difference in lung cancer risk has been associated with this enzyme difference.^Oscarson (This enzyme is also responsible for metabolizing a blood-thinning medication called coumadin).  But an even more important P-450 enzyme also differs greatly in Asians, called 2D6.  A slow-working version of this enzyme is very common in Asian populations and quite uncommon in caucasians.  An amazing list of these enzymes and medications involved, in outline form, by a former medical student named Anne Chung, is available on the 'net; you'll see the general idea and how much is known, even if the details are too technical: Chung. 

So, the point is that yes, your daughter be "more sensitive to medications" in this genetic way, due to her Asian heritage. However, she might also be "more sensitive to medications" because she is very sensitive to antidepressants, if those are the only medications (besides lithium) which you've seen a problem with so far. This might not be a genetics issue, it might be a "bipolar" issue, as that is very common. I have had several adult patients who could spring quickly toward mania with tiny doses of antidepressants, as little as 2 mg of Prozac or 1/2 of a 75 mg Wellbutrin. 

Overall, the doses of medications you've described are indeed very small.  Whatever mood stabilizer used, starting with small doses sounds like your standard approach anyway (e.g. Trileptal is usually dosed around 1200-1500). I've never seen mood experts talk about picking a mood stabilizer on the basis of ethnicity (e.g. trying to find one not metabolized by 2D6), and never thought of trying to do that myself.  Usually there are other factors driving our choices that would probably be more powerful -- desire to avoid weight gain, or need for one which could help with sleep, or antidepressant clout (that sounds particularly likely for your daughter), or cost.  Since all the doses you've named are extremely small, there's either something different about how your daughter metabolizes medications, or how she reacts to them. But in either case, you'd just have to do the same thing: start low and go up carefully. Make sure not to stop at too low a dose based on this history, though: keep going until symptoms are controlled or some limiting side effect appears, or you get to routine dose sizes -- all under the direction of the psychiatrist, of course. Good luck with that. 

Dr. Phelps

Published January, 2006