Blog | Tuesday, August 28, 2012

Contaminated truths: Wellbutrin, depression, GSK and evidence

Like any perpetually anxious physician, I had one thought when I read the jaw-droppingly obscene details about GlaxoSmithKline's briberies and deceit. Well, maybe two thoughts. The first thought was that I don't play nearly as much golf as these other doctors do.

The second thought was, "Oh my God, I hope I didn't prescribe any of these medications unnecessarily!"

And I didn't. Not really. Let me explain: one of the medications mentioned in the indictment is Wellbutrin (generic bupropion), a medication that is useful by itself for depression and smoking cessation. The evidence for these is untainted by Big Pharma, though it's susceptible to the same problems and controversies afflicting all pharmacological treatment for depression.

But another claim, which I have heard for the past few years, is that Wellbutrin is useful to "augment" pharmacological treatment for depression with SSRIs. To be honest, the claim was one of many that I have heard from colleagues that I did not verify with a good look at the evidence. (How much that we have heard from colleagues, superiors, and teachers are things we haven't verified ourselves? That's why we should be open about our biases and ignorance, and ask patients for equal measure of skepticism and trust.)

When I read the GSK doings, I decided to check and see if what I had thought true about Wellbutrin as an "augmentive" therapy actually was true. And I found out – it is, kinda. There was a randomized controlled trial in the New England Journal of Medicine of patients who had "failed" (that is, not achieved remission of their depression) with SSRIs. They compared bupropion as augmentation (that is, together with an SSRI) to buspirone as augmentation. The results were promising. As the researchers say with commendable restraint, "Augmentation of citalopram with either sustained-release bupropion or buspirone appears to be useful in actual clinical settings."

Taking a closer look, though, leads to some misgivings. There was no placebo group (i.e., patients given SSRI and a sham drug), and no group with the SSRI alone. Further, while the endpoints were specified in advance, and GSK had no active role, per the paper, in study design, authorship, or funding, the disclosure section of the article reads like an encyclopedia of pharmaceutical companies. All the authors were getting money from them all.

Do I think Wellbutrin is a useful augmentive therapy for depression? I'm not as sure as I was, after actually reading the paper. But the uncomplicated truth of its usefulness has filtered down to us, and spread throughout doctors everywhere, partially due to GSK's perfidy. Without their overpushing Wellbutrin, I might have more confidence in the possibility of genuine clinical usefulness.

How many clinical truths are contaminated by pharm money?

Zackary Berger, MD, ACP Member, is a primary care doctor and general internist in the Division of General Internal Medicine at Johns Hopkins. His research interests include doctor-patient communication, bioethics, and systematic reviews. He is also a poet, journalist and translator in Yiddish and English. This post originally appeared at his blog.