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Treament-Resistant Bipolar Maintenance, Part I

Let’s take a walk down memory lane.

It shouldn’t be hard–I provide all the memories, and, come to think of it, since you’re at your computer, you don’t really have to walk too far, either.

I began a two-part post, The Bipolar Road Less Traveled: Beyond Lithium I and Beyond Lithium II,  on how to treat treatment-resistant bipolar depression, by addressing the pivotal role lithium has played in the treatment of this illness–and the need these days, inexplicably, for something different.

It went something like this, as my cut-and-paste recalls:

“Once upon a time, if you were diagnosed with bipolar disorder, you were treated with lithium.

And, once upon a time, it worked.

According to the Report of the Surgeon General, “Success rates of 80 to 90 percent were once expected with lithium for the acute phase treatment of mania (e.g., Schou, 1989); however, lithium response rates of only 40 to 50 percent are now commonplace (Frances et al., 1996).”

Search me why this decline in effectiveness would be so, but fortunately, given that this is the case, there are a plethora of alternative psychiatric treatments for mood stability, from the anticonvulsants to the atypical antipsychotics.”

And I then went on to discuss that despite the plethora of treatments, sometimes things just stay stuck, as the bipolar patient does in depression if he has treatment-resistant bipolar depression, and then shared some of the latest treatments.

But let’s say you’ve got a different problem. Let’s say you’ve got what’s called “treatment-resistant bipolar maintenance.”

That’s right–the doctors can get you to a stable mood, and then, just when things should be fine, you’re off to the races again. You just won’t stay put. What do you do now?

Actually, it’s a challenging problem. Just when patient and doctor would like to maximize effectiveness and minimize side effects of a successful regimen, there’s no time to waste, as the patient’s flipping through moods again.

It’s difficult. Many patients will need a combination of treatments that work in conjunction to fend off either a manic or depressive episode. Many will also require more than one medication to prevent a swing to each pole. It adds up quickly, and the side effects multiply. You can keep adding and adding, and adding, hoping eventually the chemicals will assert their authority and insist your mood stay put, but it’s always best to know what the latest research recommends in terms of targeted treatment.

I imagine that a couple of the most effective ideas might not be the easiest sell–but remember that the alternative of mood instability is not really acceptable either. Ready?

Okay–clozapine. There, I’ve said it. Sometimes you can get by with it at low doses; sometimes you’ve got to boost it up to standard doses.

With one of  those scientific publication titles that I’m just wild for due to their creativity and ability to leave you hanging, “Low doses of clozapine may stabilize treatment-resistant bipolar patients” found that, well (you’ll never guess), low doses of clozapine helped stabilize (I feel foolish–can you finish the rest yourselves?). . . [See all references below.]

The problem? It’s one you already know if you’ve dealt with clozapine. Yup–it’s the side effect profile. I hesitate to go into it in great detail–and, of course, any medication could have side effects–but let me just toss out the words low white blood cell count, hypotension, seizures, muscle stiffness, just for some starters, leaving out the standard psychiatric medication side effects of weight gain, orthostasis, hyperglycemia. . .well, the point’s really been made.

It does, however, remain one of the best options. And once I’ve warmed you up on the topic of “Everybody’s Favorite Treatments,” I’ll share another of the top recommendations for treatment-resistant maintenance. It is–of course, you knew it–ECT.

Look, I’ve seen ECT work wonders, in cases where everybody had just about run out of hope, so I myself have no beef with it. But it isn’t one of those things that everyone wants a piece of, like the proverbial painless dentistry, sliced bread and indoor plumbing, or an investment slice with Bernie Madoff in the days when. . . .Well.

However, research clearly supports its efficacy in treatment-resistant bipolar (see Sienaert and Vaidya) and  Sienaert & Peuskens conclude, clear as can be, “Long-term C-ECT is an effective and safe prophylactic treatment in individual treatment-resistant patients with bipolar disorder.”

It’s hard to argue with that. I recognize, of course, that ECT can have a devastating impact on memory, and that undergoing a procedure time and again is not what people had in mind for a good time. However, maintenance ECT is excellent for the person who is medicine resistant, not complaint with medicine, or plagued by side effects.

Okay, I’ve made my plea. Let’s say you’re still cycling, and for whatever reason you won’t be on clozapine, nor will you be patiently waiting for an induced seizure week after week. There are other choices.

Let me close this post with the option of thyroid supplementation.

Yes, that’s right. And not just for the thyroid-hormonally deficient.

Useful only as an add-on treatment, levothyroxine, or T4, is a synthetic form of the thyroid hormone. And initial research has shown that adding levothyroxine supplementation to mood stabilizers increases the stabilizers’ efficiency.  That’s true regardless of the bipolar person’s actual thyroid levels.

Bauer & Whybrow studied 11 treatment-refractory bipolar patients. Levothyroxine was added to their medication regiment, and, while the patients took it, their scores on both depressive and manic symptom rating scales decreased significantly. In that 1990 study, side effects of adding the hormone were minimal.

It looks like a home-run, really. But this gets a little dicey, too, when we address the side effect issue of long-term usage. Long-term levothryoxine supplementation can potentially cause osteoporosis and cardiac arrhythmias, which can put treaters over a barrel when making the decision to use it over the long-haul.

Still flip-flopping from high to low to high and back again despite all those meds you currently take, unable to tolerate clozapine, not ready for maintenance ECT, and got no results for levothyroxine? Okay, we’ll keep digging–and meet you back, same place, same time, for a few more ideas that might just get you–finally–to stay put.


Bauer MS, Whybrow PC. Rapid cycling bipolar affective disorder. II. Treatment of refractory rapid cycling with high-dose levothyroxine: a preliminary study. Archives of General Psychiatry 1990; 47(5):435–40.

Chou James. Treatment-resistant bipolar disorder: A review of treatment approaches. Psychiatric Times 2011; 27(7):58-62.

Fehr Bettina, Ozcan M, Suppes Trisha. Low doses of clozapine may stabilize treatment-resistant bipolar patients. European Archives of Psychiatry and Clinical Neuroscience 2005; 255(1):10-14.

Muzina David, Calabrese Joseph. Rapid-cycling bipolar disorder: Which therapies are most effective?  The Journal of Family Practice 2002; 1(3).

Sienaert P, Peuskens J.  Electroconvulsive therapy: an effective therapy of medication-resistant bipolar disorder. Bipolar Disorder 2006; 8(3):304-6.

Vaidya NA, Mahableshwarkar AR, Shahid R. Continuation and maintenance ECT in treatment-resistant bipolar disorder. Journal of ECT 2003; 19(1):10-6.

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22 Responses to Treament-Resistant Bipolar Maintenance, Part I

  1. bigron42 March 27, 2012 at 9:13 am #

    I’m just a guy with a limerick reply…

    A Bipolar woman named Josephine
    Tried Lithium then she tried Clozapine
    She tried T 47,
    It sure felt like heaven,
    So she went on her trip to Aberdeen.

    Compliments of Humorous Interludes

    • Candida Abrahamson PhD March 27, 2012 at 9:26 am #

      A truly bipolar humorous interlude. I love these–particularly when the rhyme scheme calls for you to wind up in places like Aberdeen. The day’s not over–I may counter yet.

      • bigron42 March 27, 2012 at 9:44 am #

        Have at it. (Is that relly a sentence?) You are very good and a worthy opponent for my feeble gray matter.

    • Candida Abrahamson PhD March 27, 2012 at 10:05 am #

      This, I must confess, is not one of my all-time greats, and the syllabic structure is definitely long for a pure limerick–but I hate to turn down a poetry challenge! I hope you accept it as it is:

      Flipping and flopping through emotional coasts
      Desperate to settle; of stability to boast
      Clozapine: No! Seizure: Avoid!
      Already tried her mom’s Synthroid.
      Where to turn now? Aha—tomorrow’s post!

  2. Grainne March 27, 2012 at 9:18 am #

    Informative and interesting. Thanks for sharing this post.

  3. billgncs March 27, 2012 at 7:44 pm #

    All meds have side effects. I have found that without a thyroid my normal stoic composure runs the gamut of emotions. How inconvenient. Hope the levels get sorted out soon.
    Nice to know my beloved synthroid has it in for me. Where does paranoid fit in? ( smile ) probably need another pill!

    If you’ll just take this pill everyday
    You won’t run into traffic to play
    But watch out for the quake, when your heart seizes and shakes
    and the ambulance carts you away.

    • Candida Abrahamson PhD March 27, 2012 at 8:38 pm #

      True enough on the side effects–and thanks for your contribution to the limerick nonsense!

  4. theartistryofthebipolarbrain March 27, 2012 at 10:05 pm #

    Candida, thanks for your information! I am an oddity, being rapid-cycling bipolar 2. Apparently, rapid-cycling is much rarer in bipolar 2. I wasn’t aware of that, but okay. I read your previous posts on the treatment resistant bipolar depression, which I would have thought captured me more fully, but I think I will need to talk to my doc some more. And it’s interesting about the thyroid med since my grandmother had thyroid issues and they are always checking my levels. Luckily, I have a great psychiatrist who is also a pharmacokinetic specialist (I think that’s the correct title). I started with him in January and we are still adjusting meds. I will have to talk with him about all of this. Especially since I seem to be having one of the less-desirable side effects to Lithium. 🙂 Ah well, I’ll get this figured out.

    • Candida Abrahamson PhD March 28, 2012 at 8:32 am #

      Sometimes it’s like making the most complex cocktail–a little bit of this and a little less of that. . .I’m just glad you’ve got a good doctor, and hope you’ll be able to work it out, side-effect-free–soon!

    • DeeDee April 2, 2012 at 7:28 am #

      Really? Rapid cycling is uncommon in bipolar 2? I didn’t know that – count me in as another oddity, then, because I’m definitely rapid cycling. Not that my psychs ever bothered to mention that to me.

      • Candida Abrahamson PhD April 2, 2012 at 8:41 am #

        No. Sorry about the confusion. Rapid cycling is actually quite common in bipolar 2. That’s backed up consistently, but some accessible examples are at,, and even good old Wikipedia, at Just as an interesting tidbit, you’ll notice that RC is much more common among women than men. Dr. Joseph Goldberg, who has written excellent peer-reviewed articles on bipolar disorder, did a piece for medscape on RC, and, as I’m a huge fan of his, I include it here for you, too: Hope that clarifies things, Candida

      • DeeDee April 2, 2012 at 8:50 am #

        Thanks, Candida – I thought I’d seen that before.

        I expect hormones could play into rapid cycling. I certainly notice a mood drop with estrogen and progesterone levels dropping on a monthly basis. Mood stabilizers actually made that a lot more obvious because they smoothed out the rest of the background noise.

        • Candida Abrahamson PhD April 2, 2012 at 9:10 am #

          You’re spot-on again. That’s one of the significant theories on why RC is so much more common in women. The article most relevant to the issue, if you can get it, is by Ragson, Bauer & Elman, et al, called “Menstrual cycle related mood changes in women with bipolar disorder” in the 5th issue of the 2003 volume for the journal “Bipolar Disorders.” I think you’d get a lot out of it.

          • DeeDee April 2, 2012 at 9:27 am #

            Fascinating! This also jibes with my experience of oral contraceptives causing extreme mood swings. I’ve noticed that when nothing else interferes, often the precipitous drop in mood at the luteal phase is preceded by a relatively high mood as well. Very interesting.

      • theartistryofthebipolarbrain April 2, 2012 at 4:23 pm #

        That’s what the info I have read says. Don’t know how accurate it was, though. 🙂

        • Candida Abrahamson PhD April 2, 2012 at 6:29 pm #

          No worries. At least now you know not out of the norm–you’ve got lots of company, if that’s a comfort!

  5. Emily Lyons March 31, 2012 at 8:48 pm #

    I think the really good question is why so many people don’t respond to lithium anymore. One reason may be that so many people have been treated with anitdepressants prior to their bipolar diagnosis, which can worsen the course of bipolar. The other is probably that hospitals want people out so fast these days that there just isn’t enough time for a conventional mood stabilizer to kick in- antipsychotics are a bit faster (at least they can sedate you), leading to their use, and often polypharmacy, when in the past just a single mood stabilizer would have been used.

    • Candida Abrahamson PhD March 31, 2012 at 8:53 pm #

      Interesting theory about the treatment of bipolar patients with antidepressants, which can, indeed, cause switching if the person isn’t on a mood stabilizer, perhaps contributing to the severity of the illness. It’s also very likely connected to one of the unanswered questions in the psychiatric literature surrounding lack of replicability. Studies that show meds work and are effective can often not be repeated–it’s a particular problem with antidepressants. Same seems to go for lithium.

  6. DeeDee April 2, 2012 at 7:31 am #

    This is very interesting, in part because when manic symptoms first emerged for me in college, it was diagnosed as a thyroid deficiency (actually T3 and not T4, but I took T4 for awhile). The thyroid medicine really helped with the sleep-related problems of atypical depression.

    Eventually the docs said that my thyroid levels were normal and I didn’t need the meds anymore – how often does that happen? Usually when someone has thyroid problems, it’s a permanent thing. Unfortunately I can no longer remember the progression of my treatment and symptoms, since no one was paying any attention to the latter, so I don’t know if improvements in mental state were concurrent with the treatment or not.

  7. Katie April 18, 2013 at 11:25 pm #

    Think the effectiveness of lithium reducing by half has anything to do with the rise in bipolar diagnosis by 40% since the mid-90’s?

    That was my first thought. Perhaps all the cases that are difficult are not true bipolar disorder.


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