1 Boring Old Man

^{For us, STAR∗D demonstrates that treatment for depression may be less effective than advertised. After 14 weeks of citalopram (average dosage of 41.8 mg per day), 28% to 33% of participants experienced remission. A total of 50% achieved remission after a subsequent switch to or augmentation with another antidepressant. An additional 13% to 14% experienced remission after additional trials with other antidepressants or augmenting strategies. At the end of 12 months, with up to four treatment steps, roughly 70% of participants were in remission. These results are positive, especially for a population with moderate to severe depressive symptoms and substantial comorbidity. However, most placebo controlled trials report response rates of roughly 30% among depressed persons in placebo groups. It should be noted that remission rates in such placebo groups are lower than 30%. In addition, depressive episodes frequently last from six to 12 months, suggesting that some episodes among STAR∗D participants could have been self-limiting even without treatment.  Furthermore, many STAR∗D participants who achieved remission subsequently relapsed. In the absence of a placebo control group, one could argue that the results of STAR∗D demonstrate weak, transient effects of antidepressant treatment.}

^{Nevertheless, let’s assume that the results are due to medication effects and not placebo effects or nonspecific influences. Should we accept 28% remission rates after 14 weeks as success? Is a 70% remission rate at one year sufficient? How high should we set our goals for this disabling and often deadly disease? For us, the results of STAR∗D suggest that important goals remain out of reach…}

The fragment of Insel’s article may seems like a critical reading – mentioning the placebo effect and saying that we need to do better. But he mistates the results even more blatantly than the STAR*D team [70% instead of 67%]. And I expect Insel’s motive in saying that we need to do better has to do with justifying further NIMH research into depression. Insel took the reported result of STAR*D at face value instead of gasping aloud at the poor quality of the work like the rest of us. I guess if you’ve just paid $35 M for a study, you cheerlead it no matter what.

^{In general, traditional intervention research has focused on comparing how groups of individuals receiving an experimental intervention fare against a comparison group that does not receive that intervention. This approach has given us information about treatments for selected groups of people but not necessarily about how to choose the best treatment for a specific individual. We need personalized medicine: tailoring pharmacological, behavioral, and other forms of treatment to the needs of each individual. A new generation of clinical trials is needed to gather a wider array of data and examine the kinds of questions that can be used for personalized decision-making in medicine.}

^{Public trust will ultimately depend on finding better treatments, but this goal can only be reached if psychiatry finds a way for academic investigators to interact with industry without real or perceived financial conflicts of interest. New NIH regulations will increase clarity and rigorous NIMH oversight can ensure better management, but academic leaders and their professional societies will need to transform what has become a culture of influence. The greatest threat to an era of improved public health stemming from the productive and ethically sound relationship among academia, industry, and practice is a defiant embrace of the status quo, in which psychiatrists are seen as a leading source of the problem rather than as leaders in finding the solution for financial conflicts of interest.}

But my real complaint about Insel is more about what’s missing. In spite of an impressive 38 page Strategic Plan with the loftiest of goals, he strikes me as a really good speaker with nothing to say. Like his cronies, he’s a breakthrough freak [breakthrough freaks…], always swinging to knock it out of the park. He seems to be about more treatments, faster development. He can’t seem to get enough of "Translational Science" – rapidly moving things from the bench to the bedside, as they say. But I don’t hear much focus on the bench. It’s more about the "moving"  than anything else. To wit, in that article at the top of this post, he says:

^{Depression is the largest source of medical disability for Americans between 15 and 44 years of age. The National Comorbidity Survey Replication reported an annual prevalence of 6.6%, with half of the cases classified as "severe" or "very severe". Although more people are receiving treatment for mental disorders such as depression, there is no evidence that either the morbidity or mortality of these disorders has substantially changed in the past two decades…}

^{But perhaps most of all, STAR*D reminds us that we have a long way to go in the treatment of this common, disabling illness. In 2007 in the United States more prescriptions were written for antidepressants than for any other class of medication, at a cost of nearly $12 billion. Research needs to move beyond simply investigating the comparative effectiveness of current medications to pursuing the development of better treatments that will reduce the burden of illness from depression…}