Wall St. Journal, United Press International, WebMD and Time Magazine Pacific all cover the story that researchers have debunked the “chemical imbalance” claim of psychiatric drug manufacturers.

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.


_The Wall Street Journal_

November 18, 2005; Page B1



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

Hardly any patients know how Lipitor lowers cholesterol, how Lotensinreduces blood pressure, or even how ibuprofen erases headaches. Butwhen it comes to Prozac, Zoloft and Paxil, ads and glowing accounts inthe press have turned patients with depression into veritablepharmacologists, able to rattle off how these “selective serotoninreuptake inhibitors” keep more of the brain chemical serotonin hangingaround in synapses, correcting the neurochemical imbalance that causesdepression.

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 byinducing the birth and growth of new brain neurons, not by monkeyingwith serotonin. In March, a review of decades of research concludedthat something other than “changes in chemical balance might underliedepression.” And as Jeffrey Lacasse and Jonathan Leo write in PLoSMedicine, although ads for SSRIs say they correct a chemical imbalance,”there is no such thing as a scientifically correct ‘balance’ ofserotonin.”

How did so many smart people get it so wrong? Medicinal chemist DerekLowe, who works in drug development for a pharmaceutical firm, offeredan explanation in his “In the Pipeline” blog. “I worked on centralnervous system drugs for eight years, and I can confidently state thatwe know just slightly more than jack” about how antidepressants work.

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

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

There had always been data that don’t fit the serotonin-imbalancetheory. Depleting people’s serotonin levels sometimes changed theirmood for the worse and sometimes didn’t. Sending serotonin levelsthrough 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, keepingmore serotonin in the brain’s synapses. But the fact “that SSRIs act onthe serotonin system does not mean that clinical depression resultsfrom a shortage of serotonin,” says Dr. Leo, professor of anatomy atLake Erie College of Osteopathic Medicine, Bradenton, Fla. No more so,anyway, than the fact that steroid creams help rashes means that rashesare caused by a steroid shortage.

A clue to how SSRIs do work comes from how long they take to have anyeffect. They rarely make a dent in depression before three weeks, andsometimes take eight weeks to kick in. But they affect serotonin levelsright away. If depression doesn’t lift despite that serotonin hit, thedrugs must be doing something else; it’s the something else that easesdepression.

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

Claiming that depression results from a brain-chemical imbalance, asads do, is problematic on several fronts. Patients who believe this aremore likely to demand a prescription. If you have a disease caused bytoo little insulin, you take insulin; if you have one caused by toolittle 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 havebeen supplanting psychotherapy for depressed adolescents. Clinicalguidelines call for using both, and for psychotherapy to be thefirst-line treatment for most kids. Psychotherapy “can be as effectiveas medications” for major depression, concluded a study in April of 240patients, in the Archives of General Psychiatry. Numerous other studiesfind the same.

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

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

Write to Sharon Begley at sciencejournal at wsj.com

Wall St. Journal article on “chemical imbalance” fraud

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_United Press International_

Health Business

Study: Public misled by depression ads

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

The study, published in the December issue of the Public Library ofScience Medicine, focuses on manufacturers that market the cutting-edgeclass of anti-depressants known as selective serotonin reuptakeinhibitors.

The study results add to the criticism of drug companies for allegedlyfilling the airwaves with slick but deceptive advertising on variousmedications.

SSRIs can help relieve depression, but the medical evidence that theydo so by correcting low levels of serotonin in the brain is weak, andtherefore should be eliminated from direct-to-consumer ads in magazinesand on television, the study’s authors said.

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

The duo attacked the widespread use of the “serotonin theory ofdepression” in their accompanying text, saying clinical evidence doesnot adequately support the statement that serotonin imbalances in thebrain are responsible for clinical depression.

“Depression and anxiety are complicated issues that cannot be explainedin a 30-second commercial,” the authors wrote. “When the serotonintheory is portrayed with clever visual portrayals that do notaccurately represent the neuroscience research, consumers are led tobelieve that medication is necessary for the treatment for depression.”

Leo added that, contrary to the message in the ads, the prescribinginformation on the drug labels do not say that SSRIs correct serotoninimbalances.

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

“In terms of real-life effects of this advertising, we are concernedthat this oversimplified theory has become the intellectualjustification for 10-minute office visits which result in theprescription of antidepressants for a variety of ill-definedconditions,” Lacasse concluded. “In general, people need to be moreskeptical regarding claims of chemical imbalance as explanation forpsychological distress.”


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 bycorrecting a chemical imbalance in the brain? That’s being challengedin a newly published essay.

The essay’s authors say the assertion that depression results from animbalance in the brain chemical serotonin and related chemicals is notsupported by the scientific evidence.

They write that there is “a growing body of medical literature castingdoubt” on the so-called “serotonin hypothesis.” But a widely knownantidepressant 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 usefulin the treatment of mood disorders is just as strong or stronger todayas it was 13 years ago when I wrote Listening to Prozac,” he says.

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

Are Ads Misleading?

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

Millions of Americans take SSRIs for depression and other mooddisorders, and in the U.S. alone sales of the drugs top $10 billion ayear.

In a newly published essay, anatomy professor Jonathan Leo, PhD, alongwith colleague Jeffrey Lacasse, say that SSRI ads aimed at the publicare 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 serotoninbalance of the brain but adds that there is “no such thing as ascientifically established correct balance of serotonin.”

Leo cites a 2002 review which found that SSRIs were only slightly moreeffective than placebo for treating depression. He adds that efforts touse brain imaging to document chemical imbalances linked to mentalillness have proven disappointing.

He also points to studies suggesting that nondrug treatments, includingpsychotherapy and exercise, may be as effective as drugs for treatingcertain mental illnesses.

“As long as people are told about all these things I have no problemwith using these drugs,” he says. “Without a doubt, they help somepeople. Our point is that the explanation for why they work issimplistic and potentially misleading.”

Movie Star Spat

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

Leo says he hopes the paper will make the public aware that there islegitimate scientific debate about whether depression is caused bychemical 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 ofactress Brooke Shields, who wrote earlier this year that SSRIs helpedher recover from postpartum depression after the birth of her firstchild.

In a June appearance on NBC’s Today Show, Cruise called antidepressants”very dangerous” and claimed there was no proof that chemicalimbalances 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 thewhole story, it has led to the development of an important treatmentfor 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 newnerve 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 ofOsteopathic Medicine, Bradenton, FL. Peter D. Kramer, MD, clinicalprofessor of psychiatry and human behavior, Brown University,Providence, R.I. Kirsch et al, British Medical Journal. NDC Health Corp.



_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_.


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