Marcia Angell On The Epidemic Of Mental Illness
And Why Anti-Depressants Don't Work

At the NYRB.

Holy crap. And this is no kook writing. Apparently the effects of anti-depressants on depression are basically indistinguishable from the effects of "extra-strength placebos," i.e. placebos with side-effects. One hypothesis: there is simply no relevant difference in the drugs, but patients in studies with regular, inert placebos can tell whether or not they are getting the medicine, so the studies are not actually blind.

Overall, a really informative paper, marred by one minor apparent error. Angell writes:

When it was found that psychoactive drugs affect neurotransmitter levels in the brain, as evidenced mainly by the levels of their breakdown products in the spinal fluid, the theory arose that the cause of mental illness is an abnormality in the brain’s concentration of these chemicals that is specifically countered by the appropriate drug. For example, because Thorazine was found to lower dopamine levels in the brain, it was postulated that psychoses like schizophrenia are caused by too much dopamine. Or later, because certain antidepressants increase levels of the neurotransmitter serotonin in the brain, it was postulated that depression is caused by too little serotonin. (These antidepressants, like Prozac or Celexa, are called selective serotonin reuptake inhibitors (SSRIs) because they prevent the reabsorption of serotonin by the neurons that release it, so that more remains in the synapses to activate other neurons.) Thus, instead of developing a drug to treat an abnormality, an abnormality was postulated to fit a drug.

That was a great leap in logic, as all three authors point out. It was entirely possible that drugs that affected neurotransmitter levels could relieve symptoms even if neurotransmitters had nothing to do with the illness in the first place (and even possible that they relieved symptoms through some other mode of action entirely). As Carlat puts it, “By this same logic one could argue that the cause of all pain conditions is a deficiency of opiates, since narcotic pain medications activate opiate receptors in the brain.” Or similarly, one could argue that fevers are caused by too little aspirin.

Unless I'm missing something, that's a perfectly legitimate inference to a hypothesis, and in no way inconsistent with sound scientific practice. ("postulated" at the end of paragraph one probably means "hypothesized.") As Angell points out, there are plenty of objections that can be raised against how the hypothesis was tested--and that's where the action is in such cases. But there's nothing wrong with the hypothesis nor its formation--or, at least, none that's evident from the above. Also, the analogy with aspirin isn't a good one...unless the brain naturally produces aspirin.

But that's a quibble about an otherwise interesting--jaw-droppingly interesting--article.