BELOW are more media articles about how psychiatric drug ads may be misleading the public about a "chemical imbalance," from:

_Wall Street Journal_ 11/18/05

_United Press International_ 11/10/05

_WebMD_ 11/7/05

_Time Magazine Pacific_ 11/21/05

AT BOTTOM are links to the latest news about this controversy.

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_The Wall Street Journal_

November 18, 2005; Page B1

SCIENCE JOURNAL

By SHARON BEGLEY

Some Drugs Work To Treat Depression, But It Isn't Clear How

Hardly any patients know how Lipitor lowers cholesterol, how Lotensin reduces blood pressure, or even how ibuprofen erases headaches. But when it comes to Prozac, Zoloft and Paxil, ads and glowing accounts in the press have turned patients with depression into veritable pharmacologists, able to rattle off how these "selective serotonin reuptake inhibitors" keep more of the brain chemical serotonin hanging around in synapses, correcting the neurochemical imbalance that causes depression.

There is only one problem. "Not a single peer-reviewed article ... support[s] claims of serotonin deficiency in any mental disorder," scientists write in the December issue of the journal PLoS Medicine.

Indeed, a steady drip of studies have challenged the "serotonin did it" hypothesis. A 2003 mouse experiment suggested that SSRIs work by inducing the birth and growth of new brain neurons, not by monkeying with serotonin. In March, a review of decades of research concluded that something other than "changes in chemical balance might underlie depression." And as Jeffrey Lacasse and Jonathan Leo write in PLoS Medicine, although ads for SSRIs say they correct a chemical imbalance, "there is no such thing as a scientifically correct 'balance' of serotonin."

How did so many smart people get it so wrong? Medicinal chemist Derek Lowe, who works in drug development for a pharmaceutical firm, offered an explanation in his "In the Pipeline" blog. "I worked on central nervous system drugs for eight years, and I can confidently state that we know just slightly more than jack" about how antidepressants work.

It is not for lack of trying. In 1965, psychiatrist Joseph Schildkraut of Harvard University suggested that a deficiency of a brain chemical causes depression. With the success of drugs that block the reuptake of these chemicals, that idea started to look pretty good.

Yet the evidence was always circumstantial. You can't measure serotonin in the brains of living human beings. The next best thing, measuring the compounds that serotonin breaks down to in cerebrospinal fluid, suggested that clinically depressed patients had less of it than healthy people did. But it was never clear whether depression caused those low levels, or vice versa. A 2002 review of these early experiments took them to task for such flaws.

There had always been data that don't fit the serotonin-imbalance theory. Depleting people's serotonin levels sometimes changed their mood for the worse and sometimes didn't. Sending serotonin levels through the roof didn't help depression, a study found as early as 1975.

There is little doubt that the SSRIs do what their name says, keeping more serotonin in the brain's synapses. But the fact "that SSRIs act on the serotonin system does not mean that clinical depression results from a shortage of serotonin," says Dr. Leo, professor of anatomy at Lake Erie College of Osteopathic Medicine, Bradenton, Fla. No more so, anyway, than the fact that steroid creams help rashes means that rashes are caused by a steroid shortage.

A clue to how SSRIs do work comes from how long they take to have any effect. They rarely make a dent in depression before three weeks, and sometimes take eight weeks to kick in. But they affect serotonin levels right away. If depression doesn't lift despite that serotonin hit, the drugs must be doing something else; it's the something else that eases depression.

The best evidence so far is that the something else is neurogenesis -- the birth of new neurons. When scientists led by Rene Hen of Columbia University and Ronald Duman of Yale blocked neurogenesis in mice, SSRIs had no effect. When neurogenesis was unimpeded, SSRIs made the mice less anxious and depressed -- for rodents. As best scientists can tell, SSRIs first activate the serotonin system, which is somehow necessary for neurogenesis. That is what takes weeks.

Claiming that depression results from a brain-chemical imbalance, as ads do, is problematic on several fronts. Patients who believe this are more likely to demand a prescription. If you have a disease caused by too little insulin, you take insulin; if you have one caused by too little serotonin, you take serotonin boosters.

Most people treated for depression get pills rather than psychotherapy, and this week a study from Stanford University reported that drugs have been supplanting psychotherapy for depressed adolescents. Clinical guidelines call for using both, and for psychotherapy to be the first-line treatment for most kids. Psychotherapy "can be as effective as medications" for major depression, concluded a study in April of 240 patients, in the Archives of General Psychiatry. Numerous other studies find the same.

The hegemony of the serotonin hypothesis may be keeping patients from a therapy that will help them more in the long term. The relapse rate for patients on pills is higher than for those getting cognitive-behavior psychotherapy.

Some 19 million people in the U.S. suffer from depression in any given year. For many, SSRIs help little, if at all. To do better, we have to get the science right.

Write to Sharon Begley at sciencejournal at wsj.com

Wall St. Journal article on "chemical imbalance" fraud

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http://tinyurl.com/a7wwk

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_United Press International_

Health Business

Study: Public misled by depression ads

WASHINGTON, Nov. 10 (UPI) -- The most commonly prescribed anti-depressants may be effective, but drug ads are misleading about how the drugs work, a new study suggests.

The study, published in the December issue of the Public Library of Science Medicine, focuses on manufacturers that market the cutting-edge class of anti-depressants known as selective serotonin reuptake inhibitors.

The study results add to the criticism of drug companies for allegedly filling the airwaves with slick but deceptive advertising on various medications.

SSRIs can help relieve depression, but the medical evidence that they do so by correcting low levels of serotonin in the brain is weak, and therefore should be eliminated from direct-to-consumer ads in magazines and on television, the study's authors said.

The authors were Jonathan Leo, a professor of neuroanatomy at Lake Erie College of Osteopathic Medicine in Bradenton, Fla., and Jeffrey R. Lacasse, a Ph.D. candidate at Florida State University's College of Social Work.

The duo attacked the widespread use of the "serotonin theory of depression" in their accompanying text, saying clinical evidence does not adequately support the statement that serotonin imbalances in the brain are responsible for clinical depression.

"Depression and anxiety are complicated issues that cannot be explained in a 30-second commercial," the authors wrote. "When the serotonin theory is portrayed with clever visual portrayals that do not accurately represent the neuroscience research, consumers are led to believe that medication is necessary for the treatment for depression."

Leo added that, contrary to the message in the ads, the prescribing information on the drug labels do not say that SSRIs correct serotonin imbalances.

Leo and Lacasse called on the Food and Drug Administration to exercise more authority about what goes into direct-to-consumer advertising to make sure it is fair and balanced and urged people to become more active in their own care.

"In terms of real-life effects of this advertising, we are concerned that this oversimplified theory has become the intellectual justification for 10-minute office visits which result in the prescription of antidepressants for a variety of ill-defined conditions," Lacasse concluded. "In general, people need to be more skeptical regarding claims of chemical imbalance as explanation for psychological distress."

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WebMD Medical News

Essay Questions Role of Antidepressants

Authors Challenge Link Between Chemical Imbalance and Depression

By Salynn Boyles

Reviewed By Louise Chang, MD

Nov. 7, 2005 -- Do the most widely prescribed antidepressants work by correcting a chemical imbalance in the brain? That's being challenged in a newly published essay.

The essay's authors say the assertion that depression results from an imbalance in the brain chemical serotonin and related chemicals is not supported by the scientific evidence.

They write that there is "a growing body of medical literature casting doubt" on the so-called "serotonin hypothesis." But a widely known antidepressant researcher who spoke to WebMD disagrees.

Brown University psychiatry professor Peter D. Kramer, MD, is the author of Listening to Prozac and Against Depression.

"The connection between what these drugs do and what seems to be useful in the treatment of mood disorders is just as strong or stronger today as it was 13 years ago when I wrote Listening to Prozac," he says.

Kramer acknowledges that there is still much to be learned about the impact of brain chemistry on depression and other mental illnesses. He says it is unlikely that serotonin imbalance alone explains depression, but he adds that Prozac and other antidepressants that target serotonin clearly help many people.

Are Ads Misleading?

Selective serotonin reuptake inhibitors (SSRIs), include the drugs Prozac, Paxil, Zoloft, Lexapro, and Celexa. The drugs increase the availability of serotonin, which acts as a chemical messenger in the brain among other areas.

Millions of Americans take SSRIs for depression and other mood disorders, and in the U.S. alone sales of the drugs top $10 billion a year.

In a newly published essay, anatomy professor Jonathan Leo, PhD, along with colleague Jeffrey Lacasse, say that SSRI ads aimed at the public are often misleading.

Leo teaches neuroanatomy at Lake Erie College of Osteopathic Medicine in Bradenton, Fla.

"The advertising is not portraying the science in a true light," Leo tells WebMD.

He says the ads typically claim that SSRIs restore the serotonin balance of the brain but adds that there is "no such thing as a scientifically established correct balance of serotonin."

Leo cites a 2002 review which found that SSRIs were only slightly more effective than placebo for treating depression. He adds that efforts to use brain imaging to document chemical imbalances linked to mental illness have proven disappointing.

He also points to studies suggesting that nondrug treatments, including psychotherapy and exercise, may be as effective as drugs for treating certain mental illnesses.

"As long as people are told about all these things I have no problem with using these drugs," he says. "Without a doubt, they help some people. Our point is that the explanation for why they work is simplistic and potentially misleading."

Movie Star Spat

Leo and Lacasse published their essay in the December issue of the Public Library of Science journal PLoS Medicine. The Public Library of Science is a privately funded, nonprofit group that publishes scientific and medical research and makes it freely available on its web site.

Leo says he hopes the paper will make the public aware that there is legitimate scientific debate about whether depression is caused by chemical imbalance.

"Professionals have researched and debated this issue for years. It is not just a public spat between two movie stars," he says.

He is referring to actor Tom Cruise's highly publicized criticism of actress Brooke Shields, who wrote earlier this year that SSRIs helped her recover from postpartum depression after the birth of her first child.

In a June appearance on NBC's Today Show, Cruise called antidepressants "very dangerous" and claimed there was no proof that chemical imbalances in the brain drive depression.

Shields responded in a New York Times op-ed piece, calling Cruise's assertions a "ridiculous rant."

Kramer tells WebMD that while the serotonin hypothesis may not tell the whole story, it has led to the development of an important treatment for depression and other mental disorders.

"It turns out that the medicines that affect serotonin do other things, such as protect the nerve cells and enhance [the generation of new nerve cells]," he says.

SOURCES: Lacasse, J. PLoS Medicine, December 2005; vol. 2: pp. 101-106. Jonathan Leo, PhD, associate professor of anatomy, Lake Erie College of Osteopathic Medicine, Bradenton, FL. Peter D. Kramer, MD, clinical professor of psychiatry and human behavior, Brown University, Providence, R.I. Kirsch et al, British Medical Journal. NDC Health Corp.

http://www.webmd.com/content/Article/114/111406.htm

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_Time Magazine Pacific_ 21 November 2005

The cover story has two articles, too long to post here:

"Bad Medicine? — Millions of people take drugs to ward off depression. But skeptics say the pills may do more harm than good."

"Taking on the Drug Defenders": A spotlight on journalist Robert Whitaker, author of _Mad in America_.

http://www.time.com/time/pacific/magazine/0,13674,503051121,00.html

or this smaller url:

http://tinyurl.com/azqc3