The Bipolar Road Less Traveled: Beyond Lithium, Part II

Who didn’t read “The Road Not Taken” by Robert Frost in some high school English class? Perhaps you aren’t all privy, as I am as an undergraduate English major, to certain fascinating facts about it– Frost said of his own poem, “it’s a tricky poem – very tricky!” Each stanza follows an a b a a b rhyme scheme! And–now here’s a clincher–It’s in iambic tetrameter! Now aren’t you sorry you majored in something a bit more, say, practical?–but you’re probably all familiar with the closing lines about the narrator’s choice between two roads:

“I took the one less traveled by,
And that has made all the difference.”

Well, let’s say you, as a person suffering from bipolar, have tried all the standard treatments–lithium, the antidepressants, the mood stabilizers, the atypical antipsychotics–and your depression simply hasn’t remitted. (Recall from my post “Crying–Then Flying” that the amount of time the bipolar person spends in the depressive phase vastly outweighs the amount of time s/he spends manic.)

It’s horrible and crushing and every minute feels like an hour–and you understandably begin to lose hope.

But there are other treatments out there, just when you think you’ve tried everything. You simply need to take the road less traveled.

Let’s run through a few of the alternative medications to mood stabilizers, antidepressants and atypicals that psychiatrists are already beginning to use with bipolar depression, so you know there are options out there.


In his ground-breaking study on Provigil in the August 2007 issue of the American Journal of Psychiatry, Mark Frye, head of the Mayo Mood Clinic which focuses exclusively on treatment-resistant depression and bipolar disorders, and a team of researchers analyzed the use of Provigil (aka modafinil) as an adjunct to other treatments. Provigil is actually approved to treat excessive sleepiness for those who suffer from narcolepsy and shift-work sleep disorder, but Frye et al thought to add it on to the medicine regime of patients who were not sufficiently responsive to mood stabilizers.

Using the Inventory of Depressive Symptomatology as a measure, Frye and his team found a significant positive response to the addition of Provigil. As an additional benefit, Provigil did not cause patients to switch into a manic episode, which can be a hazard with the use of antidepressants.


Used to treat Parkinson’s disease, the first randomized, placebo-controlled trial (this is the phrase to have in your lexicon if you plan to attend a meeting of researchers. You’ll have hit pay dirt) on Mirapex was run by Joseph Goldberg et al and published in the March 2004 issue of (you guessed it by now) the American Journal of Psychiatry.

They studied a group of patients for whom mood stabilizers and standard antidepressants had failed. And the results looked good. 67% of patients had a reduction of 50% or more from their baselines Hamilton depression scale scores, which in this business is pretty darned good. As a positive addition, it has also been found to help reverse the cognitive impairment often suffered by bipolar patients [I’m sorry, but it seems to be true. See “Cognitive Function Across Manic or Hypomanic, Depressed, and Euthymic States in Bipolar Disorder” for just one example, or even refer back to my post on brain volume loss suffered by bipolar patients.]

[See Dr. Darvin Hege’s, a well-known Atlanta psychiatrist’s, post “Mirapex – A New Medicine for Depression”, for information from someone in the trenches.]


Rilutek is a medication used to treat Lou Gehrig’s disease. A Dr. Husseini Manji and his colleagues administered it to severely depressed bipolar patients, together with lithium, for 8 weeks. Scientists have found that effective drugs against bipolar depression boost the amount of a certain protein in (who do you think they experimented on?) rats’ brains–and Rilutek does that, too. In some of the patients Manji studied, there was almost a complete remission of symptomology–with no switching into mania. However, his study was on an extremely small number of patients, and the verdict is not yet out–and we haven’t heard yay or nay from the rats.

Interestingly enough, that’s the same Dr. Manji who’s looking into the use of tamoxifen, the breast cancer drug, for bipolar mania.


Before I address this supplement (often used as an antidote for acetaminophen poisoning, in case you want to know) I want to clarify that am not a hippy, organic, granola-ey sort of person, and particularly not when it comes to treating bipolar. This is a serious illness, and I believe it requires the use of medications. I personally don’t believe it should be treated with vitamins and herbs alone.

That having been said, there is real research out there indicating the effectiveness of n-acetylcysteine in treating bipolar depression. In the September 2008 issue of Biological Psychiatry there is a study by Berk et al of the herbal supplement that indicates it’s an effective add-on drug for bipolar depression. Medscape covered the research and noted patients taking n-acetylcysteine improved in all depression study measures.

Big plusses? No known reports of adverse side effects (and when do you hear that in discussions about bipolar medications?) and it’s a score economically, with a 60-tablet bottle of 1000 mg pills sold online by Source Naturals for $11.00. That’s probably pretty lucky, since at this point I can’t imagine your insurance covering it. [Take a look at “N-acetyl cysteine (NAC),” put out by PsychEducation.org and updated as recently as 1/12, for more helpful information.]

And actually there are more options for treatment being studied all the time (would you believe it if I told you motion sickness patches are in the running? Or producing electric fields around the brain? It’s all for real). There is hope, no matter how bad it feels, or how dark the future can look.

And if you end up using one of these treatments-hopefully to much success-just know you “took the road less traveled by.” And that, as we know, can make “all the difference.”


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