Combination T3/T4 Thyroid Hormone
(Revised June 2003; reviewed July 2004) 


Combining low dose T3 and low dose T4 seemed to help one young patient very much.  After her response I used the same approach for about 25 patients who were in some ways similar to her.  I think it helped quite a few of them too, but this is not a good way to arrive at any conclusions about whether a treatment "works" (there is too much risk of hope biasing the results, both in the patients and in the clinician).  

At that time I had not seen any clear drawbacks to this approach.  Now I've finally seen one:  an older patient clearly became worse with the treatment described below.  There are others in my "first 25" who also got worse, but it was not clearly due to the thyroid treatment.  Now I've finally seen one patient where there is no doubt:  she got worse after it was started, and got better when it was stopped, and each change was quite significant though not dangerous.  

Therefore, based only on my young patient's experience, there appear to be some patients out there who will benefit substantially from using a combination of T3 and T4 thyroid.  But there are some who will worsen, and instead do better on T4 alone, based on my older patient's experience.  

(I hope you are thinking "we're considering a treatment based on single patients' experience?"   If you've toured much of the rest of this site, I hope you've been learning to think in terms of the big research studies called randomized, controlled trials.  In this case we're talking about the very beginning of a research idea, which could easily end up a dud.   However, I've checked it out informally with some smart researchers who know about thyroid (Frye, Luechter, Roy Chengappa, Post) and nobody's said "oh forget it, that's been done, it didn't work"; or "nah, that won't work, and here's why". They've been generally encouraging of further consideration of this approach.  Too bad I'm not geared up to study this properly.  

One woman's success story

My patient Ms. B' (she encouraged me to write this up) deserves the credit for this idea, if it ever turns out to be useful.  She had years of hospitalizations, suicide attempts and constant suicidal thinking in the winter.  Summers were much better, often too good.  She would cycle rapidly, often just hoping she'd hit a "high" in time to get an entire college term's work done in a few days, after spending most of the term so low on energy she'd have trouble even getting to class.  She could not handle even a tiny dose of any antidepressant without profound energy acceleration, increased risk of self-harm of one form or another, and dramatic decreases in sleep -- even in winter, when she would need the antidepressant the most.  Light therapy helped some, but not enough.  We still desperately needed some way to help with the winter depression, and the summer agitations.  She went through all of the usual mood stabilizers, usually with a slight benefit and lots of side effect problems.  None of them helped enough to enable her to take an antidepressant.  We ended up with an unusual collaboration, casting around for options.  She taught herself quite a bit of neurochemistry in the process.  

Somehow in her research she came up with the idea of combined T3 and T4, each of which we'd tried separately.  She showed me a research study on which this whole idea hangs, from the New England Journal of Medicine, not routinely read by psychiatrists but probably the most respected medical journal in the U.S. Bunevicius (it's described in a survey of the research on this approach).  Thus there is some evidence for doing things this way, though it does not come from research in psychiatry in any but a few cases.  

After going on combined T3/T4 thyroid hormone (there are several versions), she completely stopped her rapid-cycling.  Depression remained a problem, though much less so than before.  We cautiously added buproprion (Wellbutrin SR; the generic was clearly less effective for her) and this time she could stay on it without cycling.  She even added another "natural" agent known to sometimes cause hypomania in bipolar disorder, and got away with that.  Winters were still worse, but she could function. 

This woman had suffered so much, and prior treatments had offered so little, that this change seemed almost certainly due to the thyroid.  The change followed within days of starting it, and nothing we had ever tried, even with significant hope on both our parts, had ever had an effect like this.  Of course, with a "sample size of 1", you can never completely drop your doubts.  

Several of my patients have since seemed to respond to the combination also, but none had so dramatic a response after so little previous improvement, so it is less certain that their experience represents response to the hormone.  

How is this supposed to work? 

Caution, here comes a personal opinion.  

Remember, we're comparing this combination approach, with almost no data in psychiatry to go on (just a little from endocrine research; here's that literature survey again) -- with the "supraphysiologic" approach, which does have some data on effectiveness, and also data showing that even those high doses do not seem to be associated with risk.Gyulai   So, I asked myself, what if T3 and T4 combined would do what it takes supraphysiologic doses of T4 to do?  As far as I can tell, this has not been studied -- except by my young patient Ms. B' (this would be called a "case report", if I ever got around to submitting it for publication).  

And the point of all that was:  what if we could use lower doses of the combination that didn't make a person hyperthyroid like the supraphysiologic doses do (at least by lab test, though apparently in their reports, not by symptoms experienced by their patients)?  Wouldn't that be at least as low a risk, and perhaps quite a bit lower?  We're certainly not taking much more risk than we've taken for years giving, T3 at 25 or 50 mcg doses to people with "normal" levels of T4 already present.  

Thus my personal opinion:  I think the combination approach has no more risk than currently accepted treatments, probably less, and it caused something really stunning to happen in one patient (and I think maybe a few more).  It doesn't work for everyone, and some people can get worse (just like two of my patients clearly got worse when I was trying the supraphysiologic approach), though it seems at this point not dangerously so.  When other mood stabilizer approaches have been tried, including many in combination, I consider this one, alongside the "supraphysiologic" option.    

However, one last comment before details of how I've been doing the dosing:  if you're going to discuss this with your psychiatrist, you are almost certainly going to get blank, "I don't understand" looks.  This approach is off their map, and should basically stay off until we have more data comparing it to the supraphysiologic approach.  You can try to explain it, but that probably won't work (patients have written and told me this).  You can try to find an endocrinologist, but she/he will probably pooh-pooh the combination (at least that's been the very common experience, perhaps just now beginning to change after that New England Journal article; here is an example of that controversy if you wish ). 

So why am I telling you all this, if you can't use it?  Good question.  But my philosophy is to teach patients about options, then try to collaborate on the final choice of treatment.  Maybe the thyroid issue will pry open some discussions with your doctor -- there's at least one NEJM article to cite, after all, and that's supposed to get most people's attention in my business.  But be careful out there; expect that your doctor will not wish this discussion to fall in his/her lap, and be prepared for that (here are some thoughts about how to talk with doctors about things like this).    

How do you combine T3 and T4?

There are several ways to do this.  Since both T3 and T4 have been around for years, one can simply use one pill of each type.  This may be less expensive for some people, depending on the co-pay structure of your insurance (here's a list of manufacturer's #'s for free or low cost thyroid; caution, they usually ask you to demonstrate that you can't afford to pay for it.)

Alternatively, there are two forms of combined T3 and T4 in a single pill.  These are "Thyrolar", a new synthetic form; and Armour Thyroid, which is made from pig thyroid glands.  There is a rather heated discussion going on now amongst thyroid believers and doctors about which is the best, which is the purest and varies the least, and so forth.  If you wish, here is a general discussion of your thyroid options.  Finally, here's a list of the different thyroid forms by cost, and how to "translate" from one dose type to another.