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.

Robert Whitaker writes the strongest response so far to Peter Kramer’s defense of antidepressants.

… this book. It shows a child’s hand grabbing a massive number of pills. [Scroll down to read some of the book.]

Your Child Does Not Have Bipolar Disorder is a richly deserved attack on one of Harvard University’s most prominent professors, Joseph Biederman, a man whose financially self-interested insistence on this serious diagnosis continues to damage and stigmatize millions of young children.

The book’s author, Stuart Kaplan, a professor at Penn State, also has a blog on which he worries, in a day-to-day way, about the psychiatric profession maintaining Buy-Bipolar Biederman’s regime. He notes that although the diagnosis is gradually (thanks to books like Kaplan’s, and to Biederman’s having been sanctioned for taking and not disclosing drug money) being discredited, the editors of the latest, in-progress DSMV are still saying things like this:

… ‘[C]lassic’ adult [bipolar disorder] clearly does present in pre-pubertal children as well as in adolescents, although it may be rare in the younger age group. Unambiguous agreement about this fact weighed heavily in the Work Group’s deliberations.

Kaplan goes to town on this:

The use of the wording “unambiguous agreement about this fact” is a coercive rhetorical device that has held sway for more than 15 years in the pediatric bipolar scientific literature. Instead of providing evidence, the Work Group attempts to persuade the reader that everyone who is smart and important knows this to be true. In truth the assertion is unfounded and has no place in sophisticated scientific discussions of bipolar disorder in children. The clause “although it may be rare in the younger age group” suggests some hesitation on the part of the Work Group in endorsing the existence of Bipolar Disorder in pre-pubertal children.

That the committee accepted as fact that bipolar disorder exists in children raises the issue of the use of the word fact in psychiatry as contrasted with its use in other sciences and in everyday conversation. The use of word “fact” in scientific papers in psychiatry is highly unusual. The use of the word in this context by the DSM-V Work Group is jarring to regular readers of the scholarly literature in psychiatry. In this scientific literature, papers end with conclusions preceded by discussions that are expected to point out the limitations of the scientific work. Conclusions are usually modest, tentative and limited. The word fact is almost never used.

Are there “facts” in psychiatry comparable to the physical constant of the speed of light in physics, the periodic table in chemistry, the function of the adrenal gland in biology, or the boiling point of water on the earth at sea level in everyday life? There may be some (e.g., need for an adequate environment for infants and children for psychological growth and development) but most so called facts in psychiatry are brief stand-ins or proxies for many inferences and theories that shift and change abruptly. For example, the diagnosis of bipolar disorder in adults is based to some degree on the diagnosis of Manic Depressive Insanity first developed by Kraepelin. The veracity of his observations and theories about psychosis are part of the brew of the current diagnosis of Bipolar Disorder. The diagnosis is based to limited degree on Kraepelin’s theories and a large number of other hypotheses many of which are disputable. Fact as the acceptance of some immutable truth does not enter into the discussion.

When the DSM-V Work Group refers to the unambiguous fact that the disorder exists in prepubertal children, does the Work Group have any specific age range in mind? Preschoolers? Children ages 10 years to 12 years? Children ages 6 years to 12 years? Each of these age groups has been the subject of controversy related to bipolar disorder in children, but they are lumped together without any discrimination between them. Similarly, the use of the word “rare” by the DSM-V Work Group remains inexplicably undefined. The expression “rare” has a specific meaning in medicine, referring to a prevalence of 1 or less cases per 1500. Is this what the DSM-V Work Group means? There is a startling lack of precision in the discussion of the existence of pediatric bipolar disorder in childhood by the DSM- V Work Group. Many people, myself included, believe it is closer to the truth to assume, until proven otherwise, that this prepubertal “disorder” does not exist at all.

The misdiagnosis monster lives: the stake must still be driven in to the heart of the beast.

Beast? Why the strong language?

Because the diagnosis is doing terrible things to children; and because the only people benefiting seem to be the people who sell all those pills under the child’s hand on the book’s cover.

The bipolar monster was loosed because American university professors, in cooperation with drug companies, created it. Indeed the problem that confronts us now, as Kaplan says, is how to kill it.

We’re talking Australia here (the stats for the States are probably worse); and the Australian media is beginning to wonder

1. why the country hasn’t been able to come up with prescription guidelines for this runaway train; and

2. why the committee of experts charged with this task has got in-hock-to-pharma folk on it.

Of course the underlying problem is that Australia is … a little slow. How long does it take for news to get there? We’ve known for years that Joseph Biederman’s research is compromised by his own pharma affiliations, but here comes the committee to announce that they’ve been unable to decide on the Australian guidelines because

US psychiatrist Joseph Biederman, whose work is cited over 80 times in the draft guidelines, and two colleagues were sanctioned by Harvard University after allegedly failing to report more than $1.6m they received from drug firms.

Uh… ye-e-e-s-s… Biederman’s conflicts of interest and non-disclosures and, er, “strong pro-drug views” have now gotten him into formal trouble. But Harvard took its sweet time. Everybody’s been scandalized by Biederman for ages. Where were you guys?

Meanwhile, millions of children down under get diagnosed with ADHD and have to take really strong drugs… I guess… Ho hum.

Misdeeds — from hiding study results to paying off doctors — have made Big Pharma an inviting and, frankly, an appropriate target… Antidepressants have something like celebrity status; exposing them makes headlines.

It’s not that anti-depressants have celebrity status; it’s that more Americans take them than almost any other drug. Americans of all ages, including very little children. They make headlines because they are – I and many other observers believe – massively over-prescribed.

Peter Kramer’s missing the point here, in other words. As a result, his effort, in tomorrow’s New York Times, to defend anti-depressants against Marcia Angell, Irving Kirsch, and a range of other scientists who’ve argued that they achieve only a slightly better outcome than placebos, has a vague, irrelevant feel. He complains about the limitations of the studies Angell and Kirsch cite, but these limitations aren’t particularly significant, and the studies he cites have their own limitations.

Kramer insists, for instance, that anti-depressants seem to work for “social unease.” He does not ask whether social unease is something we should think of as needing treatment. Treatment with powerful brain-altering chemicals, chemicals that have significant side effects. He does not ask what we should do about a culture in which wall-to-wall happy pill television commercials make socially uneasy people demand anti-depressant medication.

Instead, Kramer points out that “data bearing on the question is messy.” Yes, it is. But increasingly the data points toward remarkably little effect, for many of the people taking them, from anti-depressants. To say this is not to be a headline-grabber. On the contrary, it is to express a concern about the well-being of one’s fellow Americans.

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Lacking an empirical basis for his claim that anti-depressants deserve to be given to masses of people, Kramer turns to scare tactics.

[I]t is dangerous for the press to hammer away at the theme that antidepressants are placebos. They’re not. To give the impression that they are is to cause needless suffering.

No one says anti-depressants are placebos. Would that they were. People getting bad side effects from anti-depressants would be far safer taking placebos. What people are increasingly saying — and shame on the press for reporting it! — is that when it comes to lifting depression, these pills are pretty much the same as placebos. For most people, they don’t seem to do squat.

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Felix Salmon also notices the remarkably vague, not-really-there feel of Kramer’s article.

There’s an excellent overview of the gruesome mental health industry in today’s Globe and Mail.

Even as the DSM tries to be more inclusive and “dimensional,” it runs the risk of sucking millions of merely unhappy and eccentric souls into the ranks of the mentally disturbed, at vast cost.

… in the case of depression would be the practice of giving depressed people multiple anti-depressants. A recent study suggests that

Combination antidepressant treatment using 2 antidepressants appears to offer no advantage over monotherapy in patients with major depressive disorder (MDD) and may even do more harm than good, new research suggests.

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A public policy group in England responds to the amazing statistics on British women and their use of antidepressants:

These shocking figures reveal an escalating crisis in women’s use of anti-depressants. We know from working with women and girls in our centres that anti-depressants have a role to play but they are too readily prescribed as the first and only remedy. Three in five women are offered no alternatives to drugs at their reviews and one in four currently on anti-depressants have waited more than a year [to be considered for psychotherapy].

… piercing. And it ain’t pretty.

In his zeal to prove cultural bias in empirical research, Stephen Jay Gould may have been guilty of bias himself.

… he’ll have any political power anytime soon. Still – Dr. Kutcher seems to deserve a bit of scrutiny.

… deceive me…

So in love with you am I!

He was nominated for state health director, but shortly after accepting the nomination he turned it down.

He has just resigned as head of family medicine at the state university.

Allegations of medical reimbursement fraud keep following him around, but no one’s saying much.

If he is guilty of this, what an amazing, high-level instance of corruption this would have been – state health director! Even by Hawaii’s standards — it has long been one of our most corrupt states — this would have been quite an accomplishment.

Neal Palafox remains a tenured member of the UH medical faculty. I wonder how long that will last.

UD‘s buddy Bill Gleason has a honey of a post up about homeopathy and the University of Minnesota.

A lobster shell golf ball for use on cruise ships.

From The McGill Daily:

[W]hy are we so keen on defining grief as a disorder?

… The inclusion of pathological grief as a clinical diagnosis would serve to reinforce the perception of grief as a problematic, rather than a natural human reaction to loss and bereavement.

[Leeat] Granek’s concerns over the inclusion of grief in the DSM stretch beyond the realm of negative societal perceptions and attitudes. Grieving has traditionally been done in tight-knit communities made up of family, friends, and close community-members. In recent years, these support networks have shrunk or largely disappeared, which has changed the way individuals are able to grieve. Granek explains what is happening is a “diagnostic creep” which has meant that more and more people are being screened for grief “disorder.” Indeed, as Granek pointed out, anyone who has ever experienced a loss or grief falls into that purview, and can face diagnosis. As grief becomes an increasingly common diagnosis of disorder, human experiences are relegated to the institutionalized sphere: the offices of therapists, psychologists, and psychiatrists. “…

See also Edward Shorter’s recent essay.