"One More Nail In The Coffin Of Antidepressant Use In Bipolar Disorder"

That headline quotes an editorial in this month's American Journal of Psychiatry by Nassir Ghaemi, an associate professor of psychiatry at Emory University and one of the thought leaders in psychiatry on bipolar disorder. I'm beginning to like his thinking a whole lot. In recent years, he's described bipolar disorder as an existential problem and he's urged his colleagues to take the alleged child bipolar disorder with a grain of salt and proceed with due caution.

Ghaemi's editorial comes in response to a small paper in the AJP which looks at results of the STEP-BD study for bipolars with rapid cycling, generally understood as four or more episodes in a year. In other words, the nasty, gnarly crap that I see way too many people put up with, the kind of crap that four and five meds--your psychopolypharmacy from Hell--doesn't seem to cut through either. You know the story: people who are taking Lithium, Lamictal, Celexa, Prozac and Abilify all at once and don't seem to get a lot better, if at all.

The upshot of the paper is that a high percentage of patients in the STEP-BD study who had rapid cycling were also taking an anti-depressant. From the study's abstract:

"Patients who entered the study with earlier illness onset and greater severity were more likely to have one or more episodes in the prospective study year. Antidepressant use during follow-up was associated with more frequent mood episodes."

I've not been able to review the entire paper because AJP pulled my free press access recently and hasn't reinstated it yet, so if anyone has the full paper, feel free to shoot it my way. But Ghaemi basically reviewed it for all of us in his editorial, so I'm just going to quote liberally.

"In this issue of the Journal, Schneck and colleagues report new data from the NIMH-sponsored Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study, in which about one-third of the patients with bipolar disorder had rapid cycling; these patients also had more recurrences in the 1-year follow up. Only 5 percent of these rapid-cycling patients continued to meet that definition (four or more episodes in a year) at the 1-year follow up, either because of appropriate treatment in STEP-BD or because of natural history. The major predictor of worse outcome was antidepressant use, which about 60 percent of the patients received, most often accompanied by mood stabilizers.

"By focusing on the relationship between antidepressant use and rapid cycling, the STEP-BD study fills an important void. Not only is the study far larger (N=1,742) than any prior investigation, it is also prospective, unlike all but one prior observational study. Moreover, unlike that study, this STEP-BD study shows that antidepressants are associated with worsened course of illness even after adjustment for severity of baseline depression."

And:

"In my own clinical experience, most cases of refractory bipolar disorder, usually of the rapid-cycling variety, are due to the mood-destabilizing effects of antidepressants. Such patients often receive antidepressants for years, with or without mood stabilizers. They rarely receive mood stabilizers in the absence of antidepressants. If antidepressants are seen as mood destabilizers, then an adequate therapeutic trial of mood stabilizers for rapid cycling can occur only in the absence of antidepressants. Frequently, in patients with refractory rapid-cycling bipolar disorder, multiple trials of mood stabilizers appear to fail, as the data of Schneck et al. suggest, because they are evaluated with antidepressants. When antidepressants are stopped, those same mood-stabilizing agents can then be effective. Stopping antidepressants thus is the sine qua non of treating rapid-cycling bipolar disorder. Sometimes, in a minority of cases, usually with highly suicidal patients during depressive episodes, short-term antidepressant treatment may be warranted. But in most patients with rapid cycling, these mood destabilizers are best avoided." (Emphases in the original text)

And, Ghaemi points out that this isn't the classic manic switch, or mania induction from anti-depressants, that he's talking about:

"Mood destabilization with antidepressants should be distinguished from an acute manic "switch." Antidepressant-induced mania, or switch, is a short-term phenomenon; one might define it as happening within 2 months of the beginning of antidepressant treatment. Mood destabilization is a long-term phenomenon, reflecting more mood episodes over time than would have occurred by natural history. Antidepressants may cause long-term mood destabilization without a short-term manic switch, and vice versa. Although some agents may have low rates of acute manic switch, especially when used with mood stabilizers, the data from STEP-BD suggest that even the new generation of antidepressants can produce long-term mood destabilization."

And, then the bit that's got me smiling:

"In sum, like other results from STEP-BD, this study may be one more nail in the coffin of antidepressant use in bipolar disorder. It would seem rational to turn our attention from antidepressants toward better proven interventions, particularly psychotherapies, for the depressive morbidity of bipolar disorder."

Why am I smiling? Not only because I've been pointing out for about a year that in an earlier round of STEP-BD it was established that placebo beat anti-depressants in treating bipolar depression, but because I figured out in 2003 that anti-depressants simply didn't do squat for me in treating depression and seemed to agitate the heck out of me. It was about that time that I finally developed the nerve to stand up to a doc and say, "No way, Jose" to a suggestion that I take Wellbutrin. I'd just had a bad go with Lexapro and in previous years I'd had bad experiences with Prozac, Paxil and Zoloft (all in the early to mid-1990s) and lame experiences with Wellbutrin, which I took on and off from 1998 to 2002. And, I'd simply had enough of anti-depressants and told my then-doc that I didn't think they did much for bipolar disorder except cause trouble.

I'm also smiling because Ghaemi stressed the use of psychotherapy in treating bipolar depression, especially for rapid cyclers whom I am sick and tired of seeing jammed up on five meds and getting no relief.

I enjoy being right and having thoughts leaders in the field say that I was by implication. Sorta makes my day. And I'm sure it sorta doesn't make the day of the marketing departments at numerous pharmaceutical companies which make anti-depressants. And that makes me grin.

If any of you with bipolar disorder have questions about your use of anti-depressants, do one real smart thing: don't go off them without consulting with a doctor first. Then do something even smarter: when you go to see him or her, take along a copy of Ghaemi's editorial (it's linked above) and wave it at your doctor. Ask them if they have eyes and can read. Then ask for an appropriate tapering schedule for the anti-depressant you are taking.

That said, if you are diagnosed with bipolar disorder and you think anti-depressants work just fine for you in combination with a mood stabilizer, then rock on with your current meds mix.

Posted by Philip Dawdy at March 4, 2008 12:03 AM
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