1 Boring Old Man

Only the first page of this article is available on-line. The whole article summarizes Rush’s conclusions and thoughts about future directions for further clinical research. I’ve already been perhaps too vocal about what I think about STAR*D, so I’ll forgo any detailed comments on this particular version. I thought instead I’d take a shot at summarizing the STAR*D view of human depression and clinical research:

My heading, A Midsummer Night’s Dream, doesn’t refer to my opinion of the article quoted above by Dr. Rush, though maybe I do think a lot of it is fantasy based. It refers to an actual dream I must’ve had last night but don’t remember. I ran across the quoted article late last night, up trying to finally conquer lingering jet-lag. In my opinion, the article, true to form, way overvalues and over-interprets the results from the STAR*D study and reaches conclusions, many of which would usually be grist for the mill. When I awoke this morning, however, I found myself thinking about the article in a different way – not my usual grinding internal argument with the analysis or conclusions. I was thinking that these STAR*D reports are based on a way of thinking that is foreign to me. Thus my hypothesized dream. I stand by my endless complaints that the methodology and analysis is flawed, and my over-riding concern about the pharmaceutical industry’s intrusive agenda, but a lot of my angst about STAR*D and many other similar studies is a complaint about the whole system of thinking they represent [also also what’s missing]. Thus my attempt to define that system of thought.

^{What we as physicians attend to are signs and symptoms – things we see and hear about. We see these things as markers of an underlying cause, a disease. We do things [history, physical, tests] to intuit the underlying cause [diagnosis]. Treatment is aimed, if possible, at the underlying cause. In cases where the underlying cause is unknown, physicians use whatever data possible to group the signs and symptoms as if they had a unitary cause [a syndrome] and represented a disease. Research is directed towards further refining the descriptions and searching for a cause or causes. Symptomatic treatment is fine so long as it doesn’t mask the underlying cause or harm the patient. Many treatments are empirical – things found to be effective without knowing why. Other treatments are based on known medical science. There are corollaries such as preventive medicine etc.}

The STAR*D model represents a certain kind of medical thinking in situations where empiricism is the order of the day – paraphrased these days as "evidence-based medicine." When we don’t know a cause, we evaluate proposed treatments based on the measured results. We actually do the same thing when causality is known to test the effect in patients [we test an antibiotic that kills a bacteria in vitro to see if it works in vivo in infected patients]. In many medical specialties, a lot of the conditions have unknown causes [oncology, neurology, rheumatology, etc.]. In others like infectious disease or orthopedics, the specialty itself is defined by causes. Psychiatry is obviously in the first group – a specialty where most causality is unknown or speculative. I reject Dr. Insel’s redefining psychiatry as "clinical neuroscience." That’s his opinion [or wish], not a fact. I lived through a time when my former specialty, rheumatology, was seen as "clinical immunology." That was a fad, now long passed.

What my Midsummer Night’s dream must’ve been about is that the STAR*D way of thinking is just not my cup of tea. As a practicing physician, it’s incumbent on me to know as much about empirical medicine as possible. It’s my job to suggest and advise patients about the best known path for them to follow and warn them about the dangers along the way. A practicing doctor is the interface between medical science and the patient. But as a scientist, what interests me is causality and pathophysiology. I’m not conflicted about that difference. "Interest" just is what it is. A major force in my pique about modern psychiatry is that it seems to me to be only empirical, but my unknown dream told me that my "interest" was carrying too much weight in my mind. My complaint about modern psychiatry is that the pressure to understand causes, refine diagnoses, find the mechanisms of disease or treatments, seems relegated to the background. But empirical medicine is a perfectly legitimate part of medical science – applying scientific principles to validate outcomes.

That doesn’t change what I think about STAR*D. I think they’ve done a huge study on a heterogeneous diagnostic group pretending it’s a single disease. I can’t fathom how they came up with their sequencing scheme. They changed outcome parameters in mid-stream for questionable reasons and with-held the advertised parameters [which they have]. They pretended that the massive dropout rate didn’t matter, even though the subjects fled like rats on a sinking ship. It did matter. And they wrote a jillion papers in deceptive and jury-rigged ways. I honestly don’t think the study is interpretable, even if they were forthcoming. It’s lousy and distorted "empiricism." And I don’t think the cutting edge is predicting drug response with biomarkers. I see that as another piece of work driven by industry.

If that were all, I’d just say "bunk!" and move on. But that’s not what I’ve done. At my current rate, I’ll have as many blog posts about STAR*D as they have articles [that’s an exaggeration]. I think I’m using STAR*D as a way of expressing other things. My real complaint about modern psychiatry, besides the corrupting influence of industries of various flavors, is that it lacks the tension and curiosity about things unknown that drives medicine forward. For all the talk of neuroscience, what I mostly see in our literature is "product testing" and the application of any new technology of science that comes along to conditions without creative ideas and hypotheses driving the endeavor. I don’t know why people have Schizophrenia, and I want to know about that. There are thousands of similar questions, and not all of them have to do with neuroscience. I’m sure that people get depressed, have bad anxiety, or behave destructively because of things in their minds, or biographies, or lives – not in their brains. That seems self-evident to me. And I’m tired of having those of us who are interested in that causality discounted as kooks based on complaints about the early theories of Freud or the arrogance of our predecessors.