If you have so-called unipolar depression, could you possibly be bipolar waiting to happen? Perhaps you haven’t been having luck with your antidepressant. Let’s investigate.
In 2002, the NIMH began recruiting 4,000 patients with unipolar depression for the largest series of antidepressant medication trials ever conducted. The study is known as STAR*D (Sequenced Treatment Alternatives to Relieve Depression). In the first round of STAR*D, all the patients were tried on flexible doses of the SSRI Celexa. Predictably, in findings released early this year, about half failed to respond to the drug.
Fine, we know antidepressants aren’t magic bullets, but can you improve your chances of success if you try another medication approach? The second round of STAR*D was designed to found out precisely that. The 1,500 or so who did not fare well on Celexa and who elected to stay in the study were then tried on either one of three antidepressants (Zoloft, Effexor, or Wellbutrin) or a meds combination (Celexa with Wellbutrin or Celexa with the novel anxiety med Buspar). One-third of those on a second antidepressant got better, and one-quarter of those on the combo treatment got better.
So far, so good.
In July, the American Journal of Psychiatry released the third-round findings. Patients who had not responded well to earlier treatments were tried on yet another antidepressant (either the novel action Remeron or the old-generation nortryptiline). The results here were positively discouraging, between 12 and 20 percent getting better.
So what went wrong? When I first reported on the second round results in my Newsletter, Frederick Goodwin MD, former head of the NIMH and the leading mood disorders expert in the world, got back to me and informed me that the patients in STAR*D had had a mean of six depressive episodes.
In other words, most of the patients in the study experienced shorter “recurring” depressions interspersed with intervals of recovery rather than one long “chronic” depression. Dr Goodwin pointed out to me that when the pioneering diagnostician Emil Kraepelin coined the term “manic-depression,” it referred to both recurring so-called unipolar depressions and what we now call bipolar disorder.
According to Dr Goodwin, the DSM confused matters and led clinicians astray when it split manic-depression into unipolar depression and bipolar disorder.
Here’s where you need to pay close attention: When these recurring depressions are short and frequent they are “highly recurrent” and bear some semblance to the more publicized cycles of bipolar disorder. A cycle – even if “up” is only “normal” – is still a cycle. Hagop Akiskal MD of the University of California at San Diego would like to go back to Kraepelin and reclassify these highly recurrent depressions as bipolar. Dr Goodwin has proposed a more restrictive classification.
So maybe now you are beginning to see why round three failed. People with bipolar depression tend not to respond well to antidepressants. And we clearly had people in the study whose unipolar depressions behaved like bipolar depressions. These people will fail on an antidepressant just about every time. Moreover, antidepressants risk speeding up cycles, so an antidepressant may ironically result in yet more recurring depressions in a patient.
So would these individuals with highly recurrent depressions do better on bipolar meds? That’s the catch. STAR*D didn’t see this coming. There’s another catch. We simply don’t know much about treating old fashioned bipolar depression, either.
So here you are, a patient with so-called unipolar depression. You’ve failed on three antidepressants after giving them all a fair trial. What do you do? Your psychiatrist may have good reasons for trying you on yet a fourth. But if he or she fails to give you a good reason, you are entitled to suggest a mood stabilizer. Don’t feel you have to have a bipolar diagnosis to receive a bipolar med. The rationale, as Oregon psychiatrist Jim Phelps MD explained in his recent book “Why Am I Still Depressed?”, is to treat “the cycle” rather than “the symptom.”
In other words, get the cycle under control and there will be fewer depressions. It’s a pity that STAR*D failed to test this proposition. But if your antidepressant isn’t working at the moment, you’re in no position to sit around and wait five years for another study. Talk to your psychiatrist today.
Learn more about treatments for bipolar disorder.
Published On: July 27, 2006
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