… in and that’s the kicker, ain’t it? I mean, lots of people are on them; but do the little buggers actually work?

The New York Review of Books (scroll down) has for awhile been the go-to place for essays by writers who question the utility of antidepressants for many (not all – some people do benefit from some antidepressants) of the people prescribed them; but obviously, as The Guardian‘s headline suggests, the subject – as vast stretches of Europe and America chomp down on them – is very much out there.

If the very question as posed seems to you outrageous, impossible, obscene, consider for a moment the way antidepressants are made. Not that you really want to know. It’s like the thing about how sausages are made. Better not to go there.

But let’s go. Let’s ask why Louisiana’s attorney general is suing Pfizer, maker of Zoloft. For $987 million. Or so.

Attorney General Buddy Caldwell claims Zoloft is barely more effective at treating depression than a placebo, but Pfizer has persuaded doctors and consumers otherwise…

Long before Zoloft was approved by the FDA, Pfizer knew it had “serious issues with efficacy” because in early Zoloft trials, the placebo group actually had better results, the state claims.

“These early trials showed that ‘placebo still seems to be the most effective group’ and that “there is still no striking evidence of beneficial drug effect with placebo often being the superior treatment,'” the complaint states.

“Nonetheless Pfizer chose to go forward in attempting FDA approval.”

The attorney general claims that to do this, Pfizer published only information that pertained to Zoloft efficacy, and suppressed conflicting studies.

Pfizer then engaged in a “ghostwriting program to misleadingly enhance Zoloft’s credibility,” the lawsuit states. [Note: Most American med schools have no policies at all on the practice of ghostwriting among their professors.]

… Louisiana claims that despite numerous studies that show that Zoloft is “no more effective than a sugar pill at treating depression,” Pfizer’s ad campaign included a large sales force that visited healthcare professionals on a routine basis, took them out to luxurious diners and events during which salespeople promoted Zoloft.

Laissez les bons temps roulez! And as for those sad sacks – let ’em eat expensive sugar pills.

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One more note: Pfizer will settle. A thousand million dollars is nothing to Pfizer. Cost of doing business.

… an “explosive” segment on anti-depressants as no better than placebos for the vast majority of people taking them? Will it be, as promised, explosive? Harvard’s Irving Kirsch will talk about his research, featured in The Emperor’s New Clothes: Exploding the Antidepressant Myth – another promised explosion. Marcia Angell’s review of his and other books on the subject in the New York Review of Books was also, I guess, explosive… But so far that essay prompted only a flaccid little response from Peter Kramer in the New York Times.

We’ve heard nothing from the companies that make billions of dollars off the sale of do-nothing, stuffed-with-side-effects drugs except for what they told Stahl: They work. Kramer said the same thing: “[I]t is dangerous for the press to hammer away at the theme that antidepressants are placebos. They’re not.”

Dangerous!

But why are Kramer and company doing little other than repeating, while speaking darkly of risk, that antidepressants work?

Et alors. I’m not sure major attention even of the sort 60 Minutes represents will constitute a bombshell. Positions here are and have long been entrenched, and you don’t exactly kiss goodbye a ten billion dollar enterprise without a struggle.

And millions of Americans – despite witnessing an extremely loud and incredibly close prescription pill epidemic – seem wedded to a sense of themselves as chemically dependent. Indeed to a sense of life itself as the sort of thing you need Prozac to pursue.

… gets some high-profile attention.

David Brooks, New York Times:

Anybody who is on antidepressants, or knows somebody who is, should read Marcia Angell’s series “The Epidemic of Mental Illness: Why?” from The New York Review of Books. Many of us have been taught that depression arises, in part, from chemical imbalances in the brain. Apparently, there is no evidence to support that.

Many of us thought that antidepressants work. Apparently, there is meager evidence to support that, too. They may work slightly better than placebos, Angell argues, but only under certain circumstances. They may also be permanently altering people’s brains and unintentionally fueling the plague of mental illness by causing episodes of mania, for example. I wouldn’t consider Angell the last word on this, but it’s certainly a viewpoint worth learning about.

The latest study suggests antidepressants work no better than placebos.

UD‘s posts about Angell’s essays are here (scroll down).

If you’ve read Marcia Angell on antidepressants, you’re unlikely to be surprised by a recent study suggesting that “individuals who use antidepressants are much more likely to suffer relapses of major depression than those who use no medication at all… [P]eople who have not been taking any medication are at a 25 per cent risk of relapse, compared to 42 per cent or higher for those who have taken and gone off an antidepressant.” Paul Andrews, of McMaster University, argues that “antidepressants interfere with the brain’s natural self-regulation of serotonin and other neurotransmitters, and… the brain can overcorrect once medication is suspended, triggering new depression.”

In her much-discussed New York Review of Books essay, Angell reviews the similar arguments of Robert Whitaker:

If psychoactive drugs do cause harm, as Whitaker contends, what is the mechanism? The answer, he believes, lies in their effects on neurotransmitters. It is well understood that psychoactive drugs disturb neurotransmitter function, even if that was not the cause of the illness in the first place. Whitaker describes a chain of effects. When, for example, an SSRI antidepressant like Celexa increases serotonin levels in synapses, it stimulates compensatory changes through a process called negative feedback. In response to the high levels of serotonin, the neurons that secrete it (presynaptic neurons) release less of it, and the postsynaptic neurons become desensitized to it. In effect, the brain is trying to nullify the drug’s effects.

… With long-term use of psychoactive drugs, the result is, in the words of Steve Hyman, a former director of the NIMH and until recently provost of Harvard University, “substantial and long-lasting alterations in neural function.” As quoted by Whitaker, the brain, Hyman wrote, begins to function in a manner “qualitatively as well as quantitatively different from the normal state.” After several weeks on psychoactive drugs, the brain’s compensatory efforts begin to fail, and side effects emerge that reflect the mechanism of action of the drugs. For example, the SSRIs may cause episodes of mania, because of the excess of serotonin. Antipsychotics cause side effects that resemble Parkinson’s disease, because of the depletion of dopamine (which is also depleted in Parkinson’s disease). As side effects emerge, they are often treated by other drugs, and many patients end up on a cocktail of psychoactive drugs prescribed for a cocktail of diagnoses. The episodes of mania caused by antidepressants may lead to a new diagnosis of “bipolar disorder” and treatment with a “mood stabilizer,” such as Depokote (an anticonvulsant) plus one of the newer antipsychotic drugs. And so on.

Some patients take as many as six psychoactive drugs daily. 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.”*

Getting off the drugs is exceedingly difficult, according to Whitaker, because when they are withdrawn the compensatory mechanisms are left unopposed. When Celexa is withdrawn, serotonin levels fall precipitously because the presynaptic neurons are not releasing normal amounts and the postsynaptic neurons no longer have enough receptors for it. Similarly, when an antipsychotic is withdrawn, dopamine levels may skyrocket. The symptoms produced by withdrawing psychoactive drugs are often confused with relapses of the original disorder, which can lead psychiatrists to resume drug treatment, perhaps at higher doses.

“Ghosted” medical school professors – researchers who allow themselves to be named as authors of studies which are in fact all, or in part, written by ghost-writing agencies in the pay of drug firms promoting certain pills and devices – are a dime a dozen.

But not all ghosted – or in various other ways pharma-compromised – professors are created equal. When they come from our most respected universities – Harvard, Duke, Penn, Stanford – they lift a merely scummy underhanded practice all the way up to a national disgrace.

Professors are themselves of course reluctant to talk about the practice. In his withering response to Brown University professor Peter Kramer’s recent effort to defend antidepressants, Felix Salmon notes that Kramer

…takes care not to even mention part two of [Marcia] Angell’s two-part [New York Review of Books] series, where she talks at length about how psychiatry has been captured by drug companies, who “are particularly eager to win over faculty psychiatrists at prestigious academic medical centers”. (After reading Angell’s second essay, you’ll certainly wonder why Kramer doesn’t disclose how much income he gets from pharmaceutical companies.)

One of these prestigious medical centers, and the president of its university, has just hit all the papers.

[It is alleged that] five psychiatrists allowed their names to be appended to a manuscript that was drafted by medical communications company Scientific Therapeutics Information, hired by SmithKline Beecham, now GlaxoSmithKline. The paper [reportedly] misrepresented information from a research study on the antidepressant drug Paxil.

The manuscript published in the American Journal of Psychiatry in 2001, and cited many times since, suggested that Paxil may be beneficial in the treatment of bipolar depression, without acknowledging the medical communication company’s contribution or the extent of GSK’s involvement.

If any of the claims are true, it’s a really icky case: The complainant, a University of Pennsylvania professor who, along with colleagues, was involved in the research and writing of the paper, even claims that “the ghostwriting firm, Scientific Therapeutics Information in Springfield, N.J., chose [one researcher] as the paper’s first author and that Glaxo then decided to replace him with [Charles] Nemeroff.” [Background on Nemeroff here.]

Eeny meeny miny mo, who’s the biggest pharma ho? Ghost company offers one candidate; pharma co. another… Meanwhile, where are the actual, like, professors of medicine who supposedly wrote this shit? Sitting on their asses, directing their secretaries to add another ghost-written article to their hundreds and hundreds of ghost-written or guest-written articles…

Since this scandal largely involves the University of Pennsylvania, one would expect at least a word or two from its president, Amy Gutmann – especially since she chairs President Obama’s bioethics commission. Rather than traveling to Washington and generalizing about good and evil in the world of science, Gutmann should stay home, release a statement about this situation, and investigate the troubling ethical matters in her own backyard.

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Many more details here, including the shameful non-involvement of some authors of the study, and the undisclosed pharma affiliation of others.

Marcia Angell, New York Review of Books.

With long-term use of psychoactive drugs, the result is, in the words of Steve Hyman, a former director of the NIMH and until recently provost of Harvard University, “substantial and long-lasting alterations in neural function.” As quoted by Whitaker, the brain, Hyman wrote, begins to function in a manner “qualitatively as well as quantitatively different from the normal state.” After several weeks on psychoactive drugs, the brain’s compensatory efforts begin to fail, and side effects emerge that reflect the mechanism of action of the drugs… The episodes of mania caused by antidepressants may lead to a new diagnosis of “bipolar disorder” and treatment with a “mood stabilizer,” such as Depokote (an anticonvulsant) plus one of the newer antipsychotic drugs. And so on.

Some patients take as many as six psychoactive drugs daily. 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.”

Getting off the drugs is exceedingly difficult, according to Whitaker, because when they are withdrawn the compensatory mechanisms are left unopposed. When Celexa is withdrawn, serotonin levels fall precipitously because the presynaptic neurons are not releasing normal amounts and the postsynaptic neurons no longer have enough receptors for it. Similarly, when an antipsychotic is withdrawn, dopamine levels may skyrocket. The symptoms produced by withdrawing psychoactive drugs are often confused with relapses of the original disorder, which can lead psychiatrists to resume drug treatment, perhaps at higher doses.

Angell’s review of three books about psychoactive drugs and depression suggests that for the most part the pills don’t work, and are (see above) positively dangerous.

And what’s this got to do with universities? High-profile professors of psychiatry all over this country, some of them paid by drug companies, legitimize the use of these pills by millions and millions of Americans, including very small children.

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UD thanks MattF for the link.