The Bipolar Road Less Traveled: Beyond Lithium, Part I

Posted on February 2, 2012 by


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 anti-convulsants to the atypical antipsychotics.

And these seem pretty much able to control the acute phases of mania. What I’ve found, in my practice, is that the place where all hell breaks loose is in managing the soul-sucking symptoms of bipolar depression.

According to “Antidepressants for Bipolar Disorder: A Clinical Overview of Efficacy and Safety” in the Psychiatric Times, antidepressants are the most commonly used treatment in the U.S. for bipolar depression. But this in itself may help explain why so much of bipolar depression seems treatment-resistant.

Because, despite what logic and intuition would dictate, antidepressants do not seem to be the answer. Research is scarce on the effectiveness of antidepressants for bipolar depression, and most of what there is has not indicated that they have great success.

Michelle Sidor and colleagues from the University of Texas, Dallas (Journal of Clinical Psychiatry) searched the literature from 1980 to 2009 for random controlled trials (the gold star of research) and concluded that “treatment with antidepressants was . . .no better than placebo or other standard treatments.”

Happy Pills, by posterize

And in a research article with another one of those witty, innovative titles that I love (here goes), “Antidepressants ineffective in bipolar depression” in the 2007 British Medical Journal, the researchers found (all together now) that antidepressants were ineffective in treating bipolar depression.

Depressing, I know.

So some of the more standard-of-care practice in treating bipolar depression has moved into the realm of two other departments.

First, the anti-convulsant mood stabilizers have prophylactic powers against depression–so if you’re on them before you tank, your tanking should be less frequent and less profound. [That's my big plug for complying with your doctor's wishes that you take a mood stabilizer, by the way, no matter how much you squawk before you do it.] And research has shown that mood stabilizer lamictal is effective in treating the depressive pole of bipolar, so it’s often used in cases where the patient remains depressed despite use of other mood stabilizers.

Friend Two is the atypical antipsychotics, initially used in treating schizophrenia, but now approved for use in bipolar disorder, and used off-label for a variety of different ailments. They’ve taken a lot of heat–and I, for one, can perfectly well understand why–for their side effects, but when it comes to mood management, they’re certainly effective.

A growing number of studies highlight the relevance of the use of the atypicals (that’s trendy short for ‘atypical antipsychotics.’ Saves a good 5 syllables, and now you sound like you’re in the know.) for bipolar depression. For example, a 2005 paper in the Journal of Clinical Psychiatry entitled “Typical and atypical antipsychotics in bipolar depression” asserts that the atypicals now have a significant role in treating bipolar depression. And a 2007 paper that reviewed the research on the topic to date, “Atypical antipsychotics in bipolar disorder: systemic review of randomized trials” by Derry and Moore, found them as effective as any other established drug therapy.

I’m not totally clear on how the atpyicals work in treating bipolar and schizophrenia–and I may not be alone. Antipsychotics work on the dopamine system [have your eyes glazed over yet? I'm almost done for today], but that’s as far as I’ve gotten–and as far as a fair number of people–including some psychiatrists–have gotten as well.

In fact, when I asked one of my consulting psychiatrists how Geodon, an atypical used to treat both ends of the bipolar spectrum, works, he chuckled, and came out with this adaptation of a ‘dumb blonde’ joke [does it get more offensive?]:

“A blonde goes into a store and sees a shiny object. She asks the clerk, ‘What is that shiny object?’
The clerk replies, ‘That is a thermos.’ The blonde then asks, ‘What does it do?’
The clerk responds, ‘It keeps hot things hot and it keeps cold things cold.’
The blonde then says, ‘That’s amazing. How does it know which one to do?’”

And that, he said, pretty much describes the prevailing knowledge about geodon–it pulls the high pole down and lifts the low pole up–but how does it know which to do?

Inspires confidence, right?

But what if the mood stabilizers and the atypicals either haven’t worked for you, cause intolerable side effects–or just simply aren’t enough on their own?

Well, then you need to take a ride down the bipolar road less traveled.