1 Boring Old Man

^{Author’s Statement of Bias: All of this scientific objectification involved in reviewing these studies is something of a regression for me.  I left the world of hard science half my life ago, not in flight but rather because of a fascination with subjectivity. And as a practitioner, I found no real conflict between the two – depression was no exception. In my mind, depression was two things – an adjective/adverb or a noun. It was a feeling about life that colored experience and lead people to psychotherapy, the kind I did. And then there was Depression [the noun] that wasn’t a modifier of experience, it was a pervasive determinant of experience – something I thought of as biological. It didn’t take a MADRS or HAM-D to tell the difference – you can feel it in the waiting room. I guess it was sort of like Freud and Kraeplin were talking about two different things and I appreciated both views. When the Charlie Nemeroffs of the world appeared, it took me a while to understand that they talked as if all depression was a noun, a thing to be medicated as if it were a disease. Since I didn’t believe that, I drifted away from the Psychiatric world as it was in the 1990s and 2000s. Now I find myself going back over the things  I got away from. I’m biased, but I think [hope] it’s the bias of experience. When I look at these studies, I don’t think the people in these clinical trials all have Major Depressive Disorder. I’ve seen enough of MDD to know that they don’t improve like the ones in those trials on placebos. Major Depressive Disorder is a clinically distinct disease to me.}

That said, what are we to make of the claims that Seroquel XR or Abilify are indicated as an augmentation to Antidepressants in patients who don’t respond? These studies all rely on the Montgomery-Åsberg Depression Rating Scale as the primary outcome variable. It’s an observer rated ten item scale with 0-6 levels for each item [so the range of scores is 0 to 60]. I’ve included an abbreviated version of the items in this post.

This table compares the MADRS scores from the studies used by the FDA to approve Seroquel XR and Abilify as augmentation for Treatment Resistant Depression. Look in the row labeled Differences. That’s the improvement after six weeks of the Atypical Antipsychotic in the MADRS score. Then look at the MADRS items below and see if an improvement of 2.40 to 3.55 points seems that relevant on a 60 point scale. It sure doesn’t look that way to me. I say statistical but irrelevant. And when I look at the subject’s  own ratings, and I see that their ratings were not statistically significant between Placebo and Medication, I say the same thing:

They’re all in it together – Pharma, their paid physician Key Opinion Leaders who may be investigators at Clinical Research Centers that might be  affiliated with a Clinical Research Organization and might be an author who is on the Speaker’s Bureau and fronts for a medical writer who might be with a Clinical Research Organization or a Medical Writing Company etc. etc. Whatever the arrangement in a particular case, all of these elements are part of every one of these articles and Clinical Trials I’ve reviewed. And the Pharmaceutical Company pays and controls all of them.

And with this business of Augmentation of Antidepressants with Atypical Antipsychotics in Treatment Resistant Depression, they’ve really outdone themselves because it is a scientifically unsupported, unsupportable premise. Could anything be worse? Sure. It’s on the left. Chairmen of Departments and high ranking faculty members from our best academic institutions are part of this system – using Pharma money to support their Departments, schlepping around the country as Scientific Advisers, on Speaker’s Bureaus, giving CMEs, and being Journal Editors publishing these CRO-Charts. It’s downright Faustian…