May 2007 Issue [Article]

Manufacturing Depression

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A journey into the economy of melancholy

Doctor George Papakostas has some bad news for me. For the last half hour, he’s been guiding me through a catalogue of my discontent — the stalled writing projects and the weedy garden, the dwindling bank accounts and the difficulties of parenthood, the wife I see mostly in the moments before sleep or on our separate ways out the door, the typical plaint and worry and disappointment of a middle-aged, middle-class American life, which you wouldn’t bore your friends with, which you wouldn’t bore yourself with if you could avoid it and if this sweet man with his solicitous tone…

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Minor Depression is a provisional diagnosis, listed at the back of the DSM-IV, where it awaits further study. Research that uses this diagnosis thus has a twofold aim: to provide another FDA-approved indication for a particular drug and to give Minor Depression medicine’s most lucrative imprimatur — the five-digit code that allows doctors to bill insurance companies for treatment.

According to the World Health Organization, the countries with the highest consumption of fish have the lowest rates of depression. And it happens that omega-3s make cell membranes, such as the receptors in your brain that absorb serotonin and other neurotransmitters, more permeable. To a psychiatrist already convinced that depression is the result of deficiencies in serotonin transmission, the significance of this correlation outweighs any of the other possible explanations for why someone in fish-deprived France might be more prone to depression than someone in Korea or Japan.

Or too hard up for subjects. The investigators expect that it will take five years to enroll the three hundred subjects needed to complete the study.

The way that researchers decide whether these tests can accurately indicate depression is by correlating responses on them to responses on tests already known to measure depression — a good idea, unless there is no anchor at the end of the chain, in which case you may well have created a self-validating semiotic monster.

About $2.5 million over five years.

The advantage of antidepressants over placebos in those trials was an average of two points on the HAM-D, a result that could be achieved if the patient ate and slept better. The average improvement in antidepressant clinical trials is just over ten points, which means, according to Irving Kirsch, a University of Connecticut psychologist, that nearly 80 percent of the drug effect is actually a placebo effect.

In 2002, researchers observing the EEGs of patients in an antidepressant-versus-placebo trial stumbled on a pattern of brain activity common to those subjects who respond to placebos. Drug companies were very interested in this discovery, not because it allowed them to study the placebo effect but because it might allow them to identify those placebo responders and bounce them out of a trial before it starts.

Neither have they shown that in identifying the brain chemistry of a given mood or experience they have found the cause rather than the correlates; that is, they could have found the ways the brain provides, but doesn’t originate, that mood or experience.

As it happens, these are also drugs that affect serotonin. The concept of “serotonin deficiency” was invented in 1954 by two Rockefeller University scientists. In a short notice in the back of Science, they noted that LSD, whose profound effects on consciousness were well known, contained within itself a copy of the serotonin molecule, and that serotonin had recently been discovered in the brain. They speculated that a lack of serotonin, whose role in neurotransmission was still not accepted, must have something to do with mental illness.

All of which raises the question of how the doctors know what kind of follow-up to provide, whether to give a drug or not. Later, the lead investigator on the study, David Mischoulon, told me that they “take their best guess” about whether the subject was on drug or placebo. The reason for not disclosing my experimental condition, he explained, was so that doctors wouldn’t detect a pattern in the responses and thus “break the blind.” He added that I could indeed find out when the study is completed — about five years from now, he estimated.

Manufacturing Depression

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