Antidepressants & "Activation"
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Q:  Antidepressants & "Activation"

Hi, Dr. Phelps,

I have unipolar recurrent depression, and I am worried that ten years of antidepressants and combinations of antidepressants have made my illness worse. I'm now on a fairly high dose of effexor and the maximum dose of wellbutrin; plus we've recently added Geodon (the Geodon *feels* like a magic bullet, but time will tell).

I've read various descriptions of 'bipolar spectrum disorders', and I fit some of them very closely, but I don't have mania, hypomania, or euphoria of any kind :-)(well--I sort of do. See question #1).

If you can answer these two questions for me, I think it might help me figure out what to do next:

*With most antidepressants, plus Geodon, and Lamictal (which gave me a rash), I've had an initial feeling of 'activation' (that's what doctors call it, I think). I've read that activation can be a 'sign' of bipolar spectrum disorder, but am *sure* sure I heard somewhere that antidepressants are *expected* to cause activation initially. Can you help me understand this better?

**I had a period of time sixteen years ago during which I was horribly depressed, I was climbing the walls, and I was afraid to seek treatment. During this time, for example, I felt like I had to keep walking for hours on end, or the depression would 'overtake' me and be so profound that I would have to kill myself.   To me, a 'lay person', I fit the DSM IV description of a mixed episode to a T. I've tried to mention this to two different psychiatrists, but  both of them said it was not relevant because it was so long ago and because it hasn't recurred. What do you think? Should I try to bring it up again? To be honest, I'm afraid to (I know that's 'unhealthy'). I don't want to be disrespectful, and I don't want my doctor to be mad at me. Finally, I don't want to thought of as a bad patient or labeled with the dreaded 'Borderline' diagnosis.

Thanks--I'm sorry this email is so long.

Dear Ms. W' -- 
After you try a series of antidepressants and they don't work or they do but "poop out" (which itself has been suggested
represents a "soft sign" of bipolar disorder), a new strategy is worth considering anyway, namely a "consider possible bipolarity" strategy whether there are obvious symptoms  to support the diagnosis, or not.  Some people also think that obviously recurrent "unipolar" depression is a "bipolar" phenomenon simply missing the other pole, just as there are (about 10%, I believe Dr. Mauricio Tohen's work has shown) people with obvious manic episodes, thus clearly "bipolar", who never have depressed episodes, only the "one pole".  

So, I think you could say there are 3 reasons to try treating you as though you have bipolar disorder:  the "it's time for a new strategy" reason; the poop-out reason; and the recurrent unipolar reason above -- all even if you never had a symptom of hypomania at all.  

Then, figure in the fact that in many patients the hypomania can be extremely brief compared to the depression (39 to one in one recent study by Dr. Judd of the NIMH and colleagues), so that it's easily missed if you don't know exactly what you're looking for (and yet you're the one who'd have to see it, in order to report it).  And figure in the fact that some of my patients who clearly "cycle" have hypomania that looks to them as no more than briefly joining the rest of the human race in terms of energy and motivation and capacity for pleasure, and sometimes it lasts only a day or so, or even a few hours (and how are we to tell that this wasn't just a good experience and not "hypomania"?  some patients are very good at being able to tell the difference, in my experience, i.e. noting episodes where for no reason at all this happens, and often in clear association with some sleep change that also "cycles").  

After all that then we could turn to the episode you had years ago.  But since walking is known to have antidepressant effects, one could wonder whether you were just treating your depression as opposed to responding to some over-energized state that warrants considering mixed bipolar disorder.  I guess my overall sense is that there are other good reasons, above, to wonder about bipolar disorder, so that you don't have to rely on this single episode from long ago -- although if you were about in your early-to-mid 30's, so that episode was in late adolescence, then the fact that "it only occurred once" is less relevant as we know that mixed states are common in adolescents as the first way for bipolar disorder to show up (making diagnosis tricky, of course, since adolescence itself rather looks like "mixed state" bipolar disorder in numerous ways). 

And finally, do antidepressants cause "activation" in people who don't  have bipolar disorder?  Certainly not every time, as your phrasing of it implies.  In fact, it's uncommon enough to leave room to wonder whether people who exhibit that response (but not so much as to suggest hypomania, or even the vague state you'll hear referred to as "akathisia"), might be "just a little bipolar" in the sense of the bipolar spectrum way of thinking about bipolar II relative to unipolar (as you may have read in my diagnosis section on bipolar II).   Therefore, as your asking implies, there is just a little reason to wonder whether your consistent reaction is just one more small data point suggesting that your "recurrent unipolar" is a bit farther over toward bipolar than the pure unipolar end of the spectrum as your treatments thus far have been based upon. 

The good news in all this is that there may be some nifty treatment options for you when you look at mood stabilizers (as opposed to Geodon, if the magic bullet thing doesn't work out) with your doctor.   Note that even old lithium has been used as an add-on to partially effective antidepressant treatment with good results in many studies -- so you don't even have to invoke "bipolar" to try that one!  

Good luck to you. 

Dr. Phelps

Published June, 2004


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