This post is in response to Can Depression Ever be Good for You? by F. Diane Barth

Peter Kramer's favorite drug

Dedicated to Peter Kramer

Diane Barth has referenced Marcia Angell's review in the NYRB of three "anti-psychiatry" books. Barth emphasizes the sheer size of the medicalization, pharmacologization, and medication of our emotional states, and mainly the use of antidepressants by 10 percent of all Americans over the age of 6 (a figure which can only grow, since younger Americans are being medicated at a much higher rate than current adults).

Barth reflects on the meanings -- even the uses -- of depression.  But antidepressants are not the fastest growing psychiatric drug. As Angell points out, "The increased use of drugs to treat psychosis is even more dramatic. The new generation of antipsychotics, such as Risperdal, Zyprexa, and Seroquel, has replaced cholesterol-lowering agents as the top-selling class of drugs in the US." (All quotes are from Angell article unless otherwise indicated.)

The books, and their review in such a prominent publication by such a prominent medical figure (Angell is former editor of the New England Journal of Medicine), have much more to tell us. They announce the end of the psychiatric revolution.

The psychiatric revolution is "the emergence over the past four decades of the theory that mental illness is caused primarily by chemical imbalances in the brain that can be corrected by specific drugs." This revolution was spearheaded when the antidepressant "Prozac (about which Peter Kramer writes so lovingly) came to market in 1987 and was intensively promoted as a corrective for a deficiency of serotonin in the brain."

I spoke with a highly intelligent, critical-thinking young drug-policy reformer about antidepressants, which she swears by. She formed this judgment since her mother was bedridden by depression, and Prozac "cured" her. "I don't care what the studies say about the drugs," she observed, "I know they work for my mother." (I haven't followed up with the woman, so I can't say how permanent this solution has proved to be. But fall-offs from optimal performance by these medications -- sometimes quite dramatic fall-offs -- are standard.)

Such personal proof is people's gold standard -- if they see it, they believe it. But it is actually no proof at all. People around the world swear by any number of cures Americans would sneer at, along with the many "proven" therapies in the United States that have since been thoroughly discredited. This is why the FDA demands that randomly assigned subjects with a given ailment be treated with a therapy and the results compared to an untreated control group before they approve a medication for prescription to Americans.

The science and the psychology behind this are that, when people receive any psychiatric therapy, they invariably improve. There are three key reasons for this. In the first place (and this truth has been increasingly buried by the psychiatric revolution and the definition of emotional disorders as diseases), people tend to improve over time. When people enter therapy, they are often at a nadir, one from which they would rebound to a lesser or greater degree on their own no matter what is done for them.

The second reason for improvement is that people tend to respond to care, no matter what kind of attention, medication, or therapy it represents. This bias, of course, is controlled for by administering a placebo treatment to the control group of randomly assigned subjects in a therapeutic trial. The comparison between the groups allows for the calculation of the third contributor to improvement -- the value added from actual therapy.

Which is where the first of the books Angell reviews -- British academic psychologist Irving Kirsch's The Emperor's New Drugs: Exploding the Antidepressant Myth -- comes in. Broad scientific clinical trials of antidepressants have never found that much value-added from them.  The amount uncovered in such trials, if taken seriously, would stun and disillusion providers and patients alike. I would say the range is from 5%-25%, with a mean of 15%. In other words, placebo produces roughly 85% of the benefits of the actual drugs.

But with every refinement of the placebo, the drug's advantage declines. The best example is trials involving psychoactive placebos. In other words, if the placebo pill is inert, the subject experiences no chemical reaction of any kind. If the placebo is an active one, then the patient can say, "Oh, it's kicking in." When such psychoactive placebos are employed, the added improvement from antidepressants tends towards 5%.

Kirsch used the freedom-of-information act to obtain all the trials drug manufacturers conducted on the key antidepressants, which they are obligated to present to the FDA.  Many show no -- or even negative -- results. But the results aren't averaged by the FDA, who are only checking for some positive demonstrations of efficacy.  For their parts, of course, the manufacturers publish only the positive results. It was left to Kirsch and his colleagues to perform such an even-handed overall analysis of all the submitted data.  He then further partialled out the data to examine studies with active placebos and other refinements, all of which reduced the detected benefits of antidepressants.

"Kirsch reported a number of other odd findings in clinical trials of antidepressants, including the fact that there is no dose-response curve -- that is, high doses worked no better than low ones -- which is extremely unlikely for truly effective drugs. ‘Putting all this together,' writes Kirsch,

leads to the conclusion that the relatively small difference between drugs and placebos might not be a real drug effect at all. Instead, it might be an enhanced placebo effect, produced by the fact that some patients have broken [the] blind and have come to realize whether they were given drug or placebo. If this is the case, then there is no real antidepressant drug effect at all. Rather than comparing placebo to drug, we have been comparing ‘regular' placebos to ‘extra-strength' placebos."

Robert Whitaker, a well-informed and passionate journalist, has written Anatomy of an Epidemic: Magic Bullets, Psychiatric Drugs, and the Astonishing Rise of Mental Illness in America. Whitaker's point of departure is that, no matter how many more Americans with mental illness we identify and treat, the number continues to grow. After four decades when this has been true, the argument that we are simply divining people who were previously missed to receive extremely effective therapies is beginning to lose its sheen. This process seems to be self-fulfilling or, using medical terminology, iatrogenic.

This is not, strictly speaking, a scientifically based argument (as Whitaker is not scientifically trained). But Whitaker does refer to sound pharmacology when he notes that psychiatric drugs have long-term consequences that both cause the brain to rely on them (and to show withdrawal discomfort, often severe, when removed), and may actually depreciate brain functioning.  The latter conclusion is based on some extremely spooky research.  As described by Angell:

One well-respected researcher, Nancy Andreasen, and her colleagues published evidence that the use of antipsychotic drugs is associated with shrinkage of the brain, and that the effect is directly related to the dose and duration of treatment. As Andreasen explained to The New York Times, "The prefrontal cortex doesn't get the input it needs and is being shut down by drugs. That reduces the psychotic symptoms. It also causes the prefrontal cortex to slowly atrophy."

And so, Whitaker concludes, we have basically a mental-illness-causing system.

The last book reviewed, by Daniel Carlat, is Unhinged: The Trouble With Psychiatry -- A Doctor's Revelations About a Profession in Crisis. Carlat is a practicing psychiatrist, and perhaps as a result is not so radical as the other two authors can afford to be.  And yet, in his calm presentation of the realities of psychiatric practice, the influence of drug manufacturers, and the distressing long-term trends in mental illness and our inability to get a handle on it, his book may be the most alarming of all. Carlat has no axe to grind, and yet he describes American psychiatry in a way reminiscent of the American economy -- it has reached a point of declining results from which there is no return.

How does all of this reflect on the psychiatric "illness" model? None of these three authors believe the brain-chemistry-dysfunction version of reality. According to Angell:

the main problem with the theory is that after decades of trying to prove it, researchers have still come up empty-handed. All three authors document the failure of scientists to find good evidence in its favor.  Neurotransmitter function seems to be normal in people with mental illness before treatment.

Patients cannot be identified by pre-existing levels of any neurochemical or combination of them. For these authors, researchers, and Angell, the modern disease model of psychiatric illness is a myth.

Shades of Thomas Szasz.

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