Beyond ‘Beyond Lithium’–Treament-Resistant Bipolar Maintenance, Or Not Staying Put, 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.

clozapine’s structure

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.

This is levothyroxine all dressed up with no place to go. She really prefers her brand name of Synthroid.

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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