Just when you’re about to give up on your government and join the Tea Party or the Occupiers, it comes along and does something to renew your faith in the institution.

In this case, it’s a study sponsored by the National Institutes of Health and published in the Proceedings of the National Academy of Sciences, right here for free. It’s about what happened when researchers gave Paxil to rats right around the time they got pregnant. What happened to their babies, or pups, as momma rats call them

Turns out the Paxil wasn’t so good for the pups. I recommend you slog through the article, but here’s the 411.

manipulation of 5-HT during early developmentin both in vitro and in vivo models disturbs characteristic chemoarchitectural and electrophysiological brain features, including changes in raphe and callosal connections, sensory processing, and myelin sheath formation. Also, drug-exposed rat pups exhibit neophobia and disrupted juvenile play behavior.

Quick translation: Giving relatively high doses of Paxil to rat mommas early in their pregnancy makes their pups’ brains develop differently. And the pups have stranger anxiety and refrain from play more than the pups of untreated mothers. Male pups sshow these effects more than female.

The researchers argue that these results might be relevant to the increase in autism in human pups, or babies as their mommas call them. Autstic kids also tend to have stranger anxiety and trouble playing with their peers. This is a long, long leap, but it’s also really suggestive, for at least three reasons:

1. It might actually be true that among the factors fueling the autism epidemic is the depression epidemic, or should I say the antidepressant epidemic. The fact that this is even possible should be enough to bring us up short, because what it really means is that this is not something that we know the answer to. Or, to put it another way, in figuring out whether or not to approve these drugs, or to warn women about risks if they are sexually active and uncontracepted, the FDA did not look at acute effects of the SSRIs on these structures and processes. Now, you can’t expect them to look at everything, but really these findings are pretty basic, if you’re interested in what happens in early pregnancies of animals taking antidepressants. Remember, the thalidomide tragedy happened because no one, except one lonely FDA bureaucrat, thought to ask the question about in utero exposure to the drugs. So this one just goes on the long list of variables in the enormous uncontrolled experiment known as the pharmacological era. History will not judge us kindly.

2. Consider what would happen if, say, marijuana or MDMA (Ecstasy) were to turn out to cause these kinds of effects in rats. The National Institute on Drug Abuse, the Drug Czar, the Partnership for a Drug-Free America would already be carpet bombing you with more news about how dangerous these drugs are. Part of the justification for this differential treatment is that antidepressants have clinical value and illicit drugs do not. But at least pot and ecstasy do what they’re supposed to do most of the time, which is more than you can say for Paxil.

3. Psychiatric News ran a story–in the same issue that they ran a piece reporting that psychedelic drugs can change your personality for the better, like that’s news, and another resurrecting the supposedly dead neurotransmitter imbalance theory of depression –on the PNAS report. In it, a psychiatrist worried out loud that the study might “be used as a rationale for pregnant women to not use SSRIs.” As if that would be the worst thing in the world, and just another, you know, hysterical reaction to flames fanned by antipsychiatrists.

This is what psychiatrists always say when their credibility is called into question: that if people stop believing them, they will go off their meds and thus, presumably, off their rockers. But I wonder just how much proof there is about this. I mean, probably one-third of my patients are on psychotropic drugs (other than alcohol or pot, I mean). And most of them have either read my depression book or the articles I’ve written or heard me on the radio or otherwise know I’m a critic of psychiatry and of antideprssants in particular. I talk with them frequently about the topic. It’s a classic setup for someone to try to please me by going off their drugs. And do you know it has never happened? Not once has someone said, “You know, I read that thing of yours, and I’m kicking the habit.” So if it’s not happening to me, I wonder to whom it is happening. I suspect this reaction is more about psychiatrists’ wish to have a good reason to shut up their critics than it is about what actually happens in the real world.

I hate to do this, because it’s old news. But then again, so is Peter Kramer’s argument in yesterday’s Times, in which he argues that the failure of antidepressants to beat placebo in clinical trials is not an indication that the drugs don’t work. Instead he blames it on the research.

Kramer’s problem is that he has to reconcile two apparently contradictory truths: that antidepressants don’t work (according to the FDA data) and that they do (according to his, and many others’, clinical experience, including mine).

The obvious , and scientific, way to deal with this conflict is to say that the evidence that they do work is anecdotal, and that the hard numbers–37 out of 74n trials failed to detect an advantage of drug over placebo, a lousy 2-Hamilton-point aggregate advantage, etc.–tell the real story. That;s the conclusion Kirsch draws and it leads him to say that even when they do work, antidepressants work by placebo effects (amplified by the side effects).

Kramer is right to say that Kirsch’s position is ideologically motivated. he wants to believe that drugs don’t work, so he listens to prozac and hears placebo, which to me simply indicates that he (Kirsch) hasn’t taken enough serotonergic drugs. But Kramer is wrong to say that the dismal results on the trials are an artifact of poor research design, at least in the way he imagines. I suppose the problem could be poor gatekeeping, as Kramer implies, and that the samp0le popuolation in the SSRI trials isn’t sick enough, but this is a pretty lame answer, especially when there’s another one that unties this knot.
It’s true that the Hamilton was standardized on hospitalized patients. it’s also true that it was never meant to be a diagnostic test. it was meant to measure improvement in a population already identified (by Hamilton himself in the old days, by something like the SCID now) with depression who were taking tricyclics (and, probably, MAOIs). The items, more than half of them neurovegetative signs and symptoms, are tailored to the drugs. But when the drugs changed, the tests didn’t. (Note that his is a purely commercial problem–the studies Kirsch looked at were conducted the way they were because they were the way to win the FDA approval game.) And it could be that the Hamilton is a a lousy tool for measuring the effects of SSRIs.

the conclusion that the SSRIs don;t work rests on the assumption that the Hamilton is both the best way to measure depression improvement and the best way to measure the effects of SSRIs; it also assumes that depression is the proper target for the drugs. I think all these assumptions are faulty. Of course, I think the whole idea of depression as a disease is vastly overrated. That’s my prejudice. But I also think the SSRIs do work, i.e., the chemical effect of tweaking serotonin metabolism is in part a change in consciousness. But it’s not one that the Hamilton is sensitive to. That’s why the drugs seem not to work. You can’t find feathers with a magnet.

to me, this outcome is the drug companies hoist on their own petard. They didn’t have to market SSRIs as antidepressants. That was a decision made for commercial reasons as much as scientific or medical and tough luck for them. Not that it matters. They got their indication and they laughed all the way to the bank.

What’s ironic about this is that the person who has done more to prove that antidepressants don’t simply relieve people’s depression is none other than Peter Kramer. But more important is the fact that this kerfuffle is in part due to a willful blindness. There are a few studies of the effects of SSRIs on personality, indicating that wahtever antidepressant effect they have is secondary to the way they change people’s personalities, but in general there’s not much incentive to do those studies. As a society, we’re pretty chary of drugs that change personality. Think about all those ads in which Pharma promises that the drugs won'[t change who you are. That would be a tough sell. It would also turn out that if what you want to do is to transform people’s personalities, there are other serotonergic drugs that do it much better and quicker (LSD, MDMA, etc.) and without daily intake, not to mention old-fashioned psychotherapy which at least doesn’t ruin your sex life.

People sometimes ask me how I got started in the writing racket. Sometimes they’re just curious. Sometimes they’re trying to figure out how to do it themselves. The short answer to the question is that I owe it all to the Unabomber. The long answer is to be found in my first published article, which appeared in McSweeney’s in 1999 and documents my long and fraught relationship with Ted Kaczynski. It turned out to be the lazy man’s way to getting published; after the article ran, all sorts of doors suddenly opened. I’m not recommending this method, but if you want to see how to get a serial killer to run interference for you, or if you’re just curious, you can read all about it right here.

Someone could make a living (or at least a blogging) hating on David Brooks. (Indeed, someones do. Try googling “I hate David Brooks.”) Today’s column, apparently the outline for a commencement speech (is it possible that no citadel of higher learning invited Brooks to give their grads a sendoff?), is the same old thing he’s been peddling in his columns and his book for awhile now: a hash of animus toward “expressive individualism” (see Habits of the Heart for maybe the best version of this argument and for a good example of how it inevitably ends up affirming the protestant work ethic), rejection of the idea of being-over-doing (as if this were the prevailing ethic of our time, rather than a straw man put up by people who think we just don’t do enough), affirmation of “expertise,” and wishful thinking about the innate goodness of us all (especially the successful and rich), but I’ve done my hating, and I have to agree with what a friend of Mark Engler’s said: “Mocking David Brooks is somehow both the lowest of low-hanging fruit and vital to our democracy. It’s a puzzle.” An important thing to do, in other words, but one that devolves into vice the more you do it. I’ve done my bit, but I don’t want to end up needing glasses, let alone going blind, so no more.

But here’s what’s worth hating on this morning. I paid my money to the New York Times so that I can legitimately read more than twenty articles a month. I promptly forgot how much that cost me, but whatever it is, shouldn’t it exempt me from those ads that darken whatever I’m reading, splash across my screen, take forever to load in, and withhold the “click here to close” X for a mercilessly long time? At least when a cat lies down on your newspaper, it doesn’t try to get you to buy anything.

Which says a lot about both ideologies.

Anyway, that would be David Brooks, and here’s the link to my review of his book,  The Social Animal

http://www.thenation.com/article/160752/dumbest-story-ever-told-david-brooks