Tryptophan: Canadians Are Using It, Why Not We Americans?

That's a real question, not a come-on. I don't know the answer, frankly. But I'm beginning to wonder -- and maybe should have been wondering long ago. Here's why:

1. There is some evidence, not great, not a lot, but moderately consistent, that tryptophan can treat depression like Prozac (generic: fluoxetine) and the other serotonergic antidepressants.
2. Until it went off the market back in the 1990's, we were using tryptophan as a medication for sleep. It was cheap, and it seemed to work.
3. The FDA pulled it from the market because of a clear association with an unusual allergic reaction ("eosinophilic myalgia" and related problems). But since then, other countries including Canada have allowed it to be used, judging the allergic reaction problem to be related to an impurity problem since solved.
4. The FDA, however, continues to block the prescription of tryptophan in the U.S., saying that tryptophan itself might still carry some risk of this allergic reaction. Yet at the same time, they allow it to be used as a dietary supplement, including in powdered baby milk.

So, if it's okay for babies, why isn't it okay for the rest of us? I've collected a few references on this issue but would be interested to hear from anyone who has more solid information on this issue.

• The FDA announcement (2001, no updates)
• A thorough, somewhat technical review from an alternative medicine website
• A 2006 review of using 5-HTP, the next step toward serotonin from tryptophan
• A 2004 review of the "contaminant" issues

Because of a wonderful librarian, I've been able to read those last two papers listed there. The bottom line, combining the two: evidence for effectiveness is moderate; evidence for risk, due to the contaminant problem, is extremely low and not clearly a remaining risk at all, particularly using the 5-HTP approach.

What's the difference between tryptophan and 5-HTP? The latter molecule ("5-Hydroxy-Tryptophan") is the only middle step between trytophan you eat and serotonin in your brain. There are some controls on how much serotonin you end up with for a given amount of tryptophan in your diet -- but amazingly, you can push your serotonin around rather dramatically with changes in dietary tryptophan. If I get some inquiries or comments here, indicating interest (blog just started; I know it's almost invisible so far...), I can write up a simple summary of some of the chemistry.

But in closing, consider this very remarkable finding: two weeks of daily tryptophan supplements shifted "normal" volunteers toward a "positive bias" in their interpretation of facial expressions and emotional words. They noticed positive expressions more easily, and noticed negative ones less; they paid less attention to negative words; and they startled less easily. Overall they were just a little more positive in their outlook. (Interestingly, only the women experienced this effect, not the men).

Depression, especially "bipolar depression" -- more than plain depression, but not necessarily manic-depressive; explained here -- is hard to treat sometimes. And it's common. So having a simple, cheap treatment would be great. Could tryptophan, or 5-HTP, qualify as such a treatment? If there is low risk, we would need less evidence of effectiveness to justify trying it. But the risk story is still fuzzy. See why I find myself asking: Canadians are using it, why not we Americans? Do they know something we don't, about safety? Or is our FDA properly protecting us from risk?
JP

Learned Today: Medication Interactions

One of my patients seen today is taking multiple medications: quetiapine (Seroquel), lithium, carbamazepine, thyroid, and occasionally a little tiny bit of clonazepam (Klonopin). Those are just "my" medications, the ones I prescribe. (This is unfortunately not unusual: at Harvard's bipolar clinic, the average number of psych' medications their patients are taking is four) She's also taking diovan, verapamil, omeprazole, HCTZ, and Relafen from her primary care doctor. You don't have to recognize those medication names to see the problem, which pharmaco-experts are always warning about: the potential for interactions between drugs.

In case you've not already found one, here's a relatively simple medication-interaction checker. But before you get too excited: the problem is the interactions you'll find listed are too inclusive. Lots of interactions listed here are theoretical more than real. The computer lists things that in clinical practice just don't really cause much trouble. So you, a patient or family member, might see some interaction listed and think there's something to worry about when a doctor who's used these medications for years knows it's not a common problem.

For example, in my patient's case, carbamazepine's potential "neurologic side effects" are more likely when used in combination with lithium. This interaction shows up on most lists; on the checker linked above, it is said to be "moderate in severity". But it is also "poorly documented", which I presume reflects the fact that we who use these two together only rarely see any evidence of this problem. It's nice for me to know about, but for you to worry about? No, and that's why I would only recommend these drug interaction checkers to patients and families with caution.

If your doctor is in a hurry (whose isn't?), you could cause trouble by asking her/him to review a list of medication interactions you printed out. On the other hand, interactions -- as could occur between several of the medications my patient today is taking -- are worth checking: by somebody, at some point. So if you think maybe your doctor hasn't had time to run a check; and if you have a good enough relationship to carefully raise the issue of interactions without ruining your connection with this doc'; then you might want to run your medications through a checking program such as the one listed above.

Doctors really don't have a good system for monitoring for interactions, and patients/families could become a useful part of the team by running these checks and bringing in the list for review -- as long as they understand that some of the interactions will be minor, or "poorly documented", and can be safely ignored in the majority of cases. Obviously the best time to run that check would be each time a new medication was going to be added to the list, before that medication was started. But here's where you have to remember: the point of the list is to make one think, and consider what's known, not to raise a red flag about every potential interaction (because the programs are not good at telling which issues merit a red flag or a yellow one or a green one!).

So you might say to the doc's nurse: "I really trust Dr. Jones' judgment, and I want to take this medication with confidence, so I'd just like to make sure that the medication interactions I've found are minor and not an issue we need to worry about, as I understand is common with these lists. Can you just check with Dr. Jones and make sure there's nothing here to worry about? I'll assume that unless I hear back from you, I should go ahead with this new medication. I can email you the list if you like" [cut/paste]. You'll see that this approach is similar to the general approach outlined in my essay on Talking with Doctors. It's tricky. It's new. Still a good idea, I think, but blame me if your doctor doesn't like it, and be prepared for that to happen! Good luck with the process.