that a placebo sugar pill was slightly more effective, and St John's Wort as

effective, in helping folks with depression than traditional meds:

belief (in recovery) is a critical factor in promoting relief.

Placebo nation

Baltimore Sun Editorial May 18, 2002

IN PILLS we trust. The latest mood-altering prescription medicines. Sugar

pills. No matter.

Such is the latest word from the final frontier, the vast unknown of the

space between our ears. Like the far reaches of outer space, here is where we

confront the most profound questions. Who are we? What afflicts us? How to

heal it?

Not that long ago, people with serious mental problems were locked up or

exiled to the wilds. Depressive malaises were attributed to failures of will

or morality. Then a certain Viennese doctor, himself prone to altering his

state of mind with cocaine, launched us down the long and winding road of

talk therapy.

And then came the latest generation of antidepressants, mood-elevating

psychotropics so well refined and marketed over the past 15 years that they

have become embedded in our cultural woodwork. Aggressive salesmanship has

produced a remarkable degree of social acceptability for these drugs, not to

mention more than $12 billion in revenue from the U.S. market last year.

What a natural fit for the baby boom generation, which came of age along with

a cafeteria of recreational drugs. What a perfect fit for the world of

managed health care, pills being a whole lot cheaper than therapists. What a

tailored fit for our age of ever more instant gratification.

Make no mistake, major depression is a terrible disease that affects tens of

millions of Americans, who annually gobble up more than 10 million

prescriptions a year for various antidepressants -- a tally that's been

growing by leaps and bounds. This category of drugs now accounts for more

than 8 percent of all prescription revenue, the single biggest source.

No doubt, these drugs -- Prozac, Zoloft and the like -- have helped many,

though far from everyone who has taken them, including some who have had

negative reactions. And of course, it has long been noted that their

pervasive use can be likened to the role of soma, the stay happy, productive

and unquestioning drug in Brave New World, Aldous Huxley's frightful vision

of the future.

Now a new study published in The American Journal of Psychiatry shows that

sugar pills work about the same -- or even better -- than antidepressants in

terms of patients' reports of improved moods.

Significantly, that study also found that the placebos tended to produce some

of the same changes as antidepressants in the prefrontal cortex, the region

of the brain believed to play a big role in controlling moods. This sort of

placebo effect is not new, but some researchers are finding that, in studies

of antidepressants, it has grown stronger over the last two decades.

It's as if we're prone to believe that pills -- any pills -- will help us,

and that belief produces relief.

There are a lot of fine points here. Real pills and sugar pills may work in

different ways, researchers say. In the new study in which placebos did as

well, if not better, than antidepressants, all patients got hours of

attention from medical professionals; by contrast, the vast majority of

people taking antidepressants see primary-care physicians for relatively

short visits involving little talk therapy.

Some researchers now believe that points us back virtually full circle -- to

the value of talking out our problems, our depressions. Hello again, Dr.

Freud. But don't look for the use of antidepressants to do anything but

become more widespread. In other words, we're still listening to Prozac but

we still don't have much of a clue about what it's saying.

Source:

http://www.sunspot.net/news/opinion/bal-ed.placebo18may18.story?coll=bal%2Dopinion%2Dheadlines

Editorial: Depression / Just a pill full of sugar . . . ?

Minneapolis St. Paul Star Tribune May 14, 2002

You've been feeling bluer than blue for far too long, and even going to the

dry cleaner is getting to be too much. You're depressed, and you know it. You

have just enough energy to trudge to the doctor for a Prozac prescription,

but now you're wondering if you should: What about the new study showing that

sugar pills work just as well as antidepressants? Shouldn't you skip the

doctor and grab a bag of M&Ms?

Don't even think about it. As fascinating as the new findings about placebo

power may be, they don't disprove the value of seeking treatment for

depression. The most spurious -- and dangerous -- conclusion to be drawn from

the sugar-pill study is that antidepressants don't work or that depression

isn't a real disease. Neither notion is true.

Quite the contrary: All sorts of research shows that depression is a bona

fide brain disorder, as detectable as it is disabling. Many medications have

been shown to relieve its symptoms by adjusting brain chemistry.

Yet here's the puzzle: In half of antidepressant trials conducted by drug

companies between 1979 and 1996, patients given sugar pills were just as

likely to experience relief as those given antidepressants. Drawn from a

Seattle psychiatrist's analysis of 96 drug trials, this finding seems to

raise questions about drugs long thought to work wonders. The doubts are

magnified by news that the "dud pills," like antidepressants, seem to produce

a documentable change in brain activity -- not just in mood.

Does this mean it's time to switch to sugar pills? Not at all. The placebo

effect -- the fact that some patients will improve if given any sort of

treatment at all, even a fake pill -- is an accepted truth of modern

medicine. It's long been known that the power of suggestion can lower blood

pressure, relieve asthma, reduce pain -- even minimize the tremors of

Parkinson's disease. But suggestion, it seems, is more than an idea: It's

almost a treatment in itself -- changing how the brain works.

It's not so surprising, really. As many researchers have noted, the

biochemistry of mood is astonishingly complex. It can be influenced by genes

and environment, trauma and loneliness, interaction and touch. Mood disorders

come in many guises, demand careful diagnosis and respond to an array of

therapies. Indeed, one thing worth noting about the clinical trials'

sugar-pill takers is their unusual "treatment" setting: The average

participant in a typical eight-week drug trial spent about 20 hours being

examined by highly trained caregivers -- thereby absorbing a dose of personal

attention that could itself raise levels of serotonin, dopamine and other

mood-lifting neurotransmitters. Yet most people suffering from depression get

nowhere near that kind of attention: They're seen by primary-care doctors for

perhaps 20 minutes a month -- often less.

More than a few onlookers have seized on the sugar-pill study with glee and

guffaws -- making much of the old news that placebos actually seem to work.

It's true; they do -- but usually only for a while. Over the long haul,

anyone with severe depression is far better off taking real medicine in

combination with psychotherapy.

In fact, as a psychiatrist at Columbia University said this week, wider

antidepressant use may even be driving down the nation's suicide rate. From

1995 to 1998, his new analysis shows, prescriptions for new antidepressants

like Prozac rose 41 percent -- while the nation's suicide rate dipped about 6

percent. Even more heartening is the 27 percent drop in the suicide rate for

teenagers -- an age group whose rate had tripled between 1955 and 1985.

It's always difficult to link happy effects with certain causes, but the

correlation between surging antidepressant use and a suicide downturn

shouldn't be sniffed at. It's possible, of course, that a bit of the dip was

due to placebos. But tell that to the multitude of Americans who credit

antidepressants with restoring their health. Think they'll give sugar pills a

try? Not on their lives.

Source: http://www.startribune.com/stories/561/2832250.html

Why Depressed Patients Respond to Placebo

Health Media Ltd - May 08, 2002

Both placebo and antidepressant share a common pattern of cortical glucose

metabolism increases and limbic-paralimbic metabolism decreases, report Dr

Helen Mayberg and her team from the University of Texas.

Administration of placebo can result in a clinical response indistinguishable

from that seen with active antidepressant treatment, but the underlying

functional brain correlates of this phenomenon have not been fully

characterised.

The University of Texas researchers studied a group of 17 middle-aged

medication-free men hospitalised for depression. These men were given either

the selective serotonin reuptake inhibitor fluoxetine or a placebo for six

weeks in a double-blind manner. Additionally, all patients received the

therapeutic benefits of being hospitalised on a standard ward, such as daily

individual meetings with the treating physician, group therapy and various

ward activities.

Changes in brain glucose metabolism were measured by using positron emission

tomography. In total, 15 men completed the study and symptom remission was

found in 8 of the men. Analysis revealed that four of the responsive men had

received the placebo and the same number improved with active medication.

Similar changes in brain glucose metabolism were seen in both the men

responsive to placebo and those responsive to antidepressant.

However, the patients who received the antidepressant showed additional

changes in the brainstem, striatum and hippocampus. The researchers also

point out that responding to a placebo as a result of "expectation" of

successful treatment is a well-recognised phenomenon. Dr Mayberg and

colleagues believe that the common brain patterns seen in placebo and

antidepressant responders suggests that facilitation of these changes may be

necessary for depression remission, regardless of treatment modality.

Writing in the American Journal of Psychiatry, the study authors said, "The

combination of dorsal-cortical increases and limbic-paralimbic decreases in

glucose metabolism, with response to both drug and placebo intervention,

suggests that therapy for depression targeting either subcortical (brainstem)

or cortical (frontal-posterior cingulate) sites should be equally effective

if there is a preserved compensatory capacity in the obligatory circuit

overall." Reference: Mayberg et al, American Journal of Psychiatry

2002;159:728-737

Against Depression, a Sugar Pill Is Hard to Beat
Placebos Improve Mood, Change Brain Chemistry in Majority of Trials of
Antidepressants

By Shankar Vedantam
Washington Post Staff Writer
Tuesday, May 7, 2002; Page A01

After thousands of studies, hundreds of millions of prescriptions and tens of
billions of dollars in sales, two things are certain about pills that treat
depression: Antidepressants like Prozac, Paxil and Zoloft work. And so do
sugar pills.

A new analysis has found that in the majority of trials conducted by drug companies in recent decades, sugar pills have done as well as -- or better than -- antidepressants. Companies have had to conduct numerous trials to get two that show a positive result, which is the Food and Drug Administration's minimum for approval.

What's more, the sugar pills, or placebos, cause profound changes in the same
areas of the brain affected by the medicines, according to research published
last week. One researcher has ruefully concluded that a higher percentage of
depressed patients get better on placebos today than 20 years ago.

Placebos -- or dud pills -- have long been used to help scientists separate
the "real" effectiveness of medicines from the "illusory" feelings of
patients. The placebo effect -- the phenomenon of patients feeling better
after they've been treated with dud pills -- is seen throughout the field of
medicine. But new research suggests that the placebo may play an
extraordinary role in the treatment of depression -- where how people feel
spells the difference between sickness and health.

The new research may shed light on findings such as those from a trial last
month that compared the herbal remedy St. John's wort against Zoloft. St.
John's wort fully cured 24 percent of the depressed people who received it,
and Zoloft cured 25 percent -- but the placebo fully cured 32 percent.

The confounding and controversial findings do not mean that antidepressants
do not work. But clinicians and researchers say the results do suggest that
Americans may be overestimating the power of the drugs, and that the
medicines' greatest benefits may come from the care and concern shown to
patients during a clinical trial -- a context that does not exist for
millions of patients using the drugs in the real world.

"The drugs work, and I prescribe them, but they are not what they are cracked
up to be," said Wayne Blackmon, a Washington psychiatrist whose practice
largely comprises patients who suffer from depression. "I know from clinical
experience the drugs alone don't do the job."

Still, drugs may have become the reflexive treatment for the vast majority of
Americans receiving medical attention for depression: As the number of doctor
visits for depression rose from 14 million in 1987 to almost 25 million last
year, medications were prescribed for nine in 10 patients, according to
research published last week.

It is not clear how many patients received medicines in a context of therapy,
although research has indicated that combining medicines with psychotherapy
produces the best results.

But Randall Stafford, the Stanford University physician who conducted the
study on doctor visits, found that less than one-third of them in 2001 were
to psychiatrists and two-thirds of them were to primary care physicians. The
former are more likely to situate the medicines in a larger context of
therapy, while the latter are less knowledgeable about therapy, more pressed
for time and less likely to offer patients anything like the attention they
would receive in a clinical trial.

The average participant in an eight-week trial spends about 20 hours being
examined by top experts and highly trained caregivers, said Seattle
psychiatrist Arif Khan, who studied the placebo effect in trials submitted to
the FDA. Participants -- including those being given sugar pills -- are asked
detailed questions about how they are feeling, and their every psychological
change is closely noted.

In comparison, Khan noted, the average patient with depression sees a doctor
perhaps 20 minutes a month.

His analysis of 96 antidepressant trials between 1979 and 1996 showed that in
52 percent of them, the effect of the antidepressant could not be
distinguished from that of the placebo. Khan said the makers of Prozac had to
run five trials to obtain two that were positive, and the makers of Paxil and
Zoloft had to run even more. He analyzed trials that were made public in the
medical literature, which tend to show positive results, and those that were
not.

"It speaks to the difficulty we have in classifying and identifying the
disorders we deal with," said Thomas Laughren, who heads the group of
scientists at the FDA that evaluates the medicines. "Psychiatric diagnosis is
descriptive. We don't really understand psychiatric disorders at a biological
level."

Patients with similar symptoms, he explained, may have different problems
with their brain chemistry. Scientists don't understand the neural mechanisms
of depression -- or why medicines like Prozac and Paxil work.

"We like to think we give people treatments and they get better," said Andrew
Leuchter, a professor of psychiatry at UCLA. "We have this fallacy of
success, but we don't know in any individual why they get better. Undoubtedly
one of those factors is the time we spend with people and the connectedness
that gives patients."

In January, Leuchter published a study in the American Journal of Psychiatry,
in which he tracked some of the brain changes associated with drugs such as
Prozac and Effexor, which are called selective serotonin reuptake inhibitors.
When Leuchter compared the brain changes in patients on placebos, he was
amazed to find that many of them had changes in the same parts of the brain
that are thought to control important facets of mood.

Patients who got better on placebos showed heightened activity in the
prefrontal lobe, and that activity continued to rise during the eight weeks
of the study. Those who responded to medicine initially showed a decline in
prefrontal brain activity, then a rise that eventually tapered off.
Thirty-eight percent of patients responded to the placebo, and 52 percent to
the medicines.

Once the trial was over and the patients who had been given placebos were
told as much, they quickly deteriorated. People's belief in the power of
antidepressants may explain why they do well on placebos. Patients in trials
are not told which they are receiving.

Likewise, sea changes in the treatment of depression -- including the
reduction in the stigma attached to mental illness, the widespread use of
antidepressants and the immense marketing efforts by their manufacturers --
may explain why Timothy Walsh, a psychiatrist at Columbia University,
recently found that the placebo effect has grown in recent years. He found
that greater percentages of people tended to get better on placebos during
trials of antidepressants in 2000 than in 1981.

Some observers assert that the medicines themselves work because of the
placebo effect, but most psychiatrists believe the drugs do have an effect of
their own. Drugs are a "placebo-plus" treatment, said Helen Mayberg, head of
neuropsychiatry at the Rotman Research Institute at the University of
Toronto.

In a study published last week in the American Journal of Psychiatry, Mayberg
evaluated brain changes during trials using a sophisticated brain imaging
technique. She found that medicines, besides working on areas that are
activated by placebos, also work on areas deep in the brain stem, the
hippocampus and striatum.

Since both depression and the effect of the medicines are still not well
understood, it's not clear what these changes mean. While they could be
irrelevant effects, Mayberg said a better explanation is that the drugs
affect areas deep within the brain and then work upward to affect parts of
the brain that control mood. Placebos may work in the reverse direction. In
part, this may explain why drug effects tend to be more reliable than
placebos in the long run.

Mayberg likened depression to a room with a hole in one window.

"You are trying to set a thermostat -- it's 100 degrees outside and you want
it to be 70," she said. "If you set the thermostat to 70, that doesn't work.
But if I set my thermostat to 50, that fools the system and gets the
temperature back to 70."

Both drugs and placebos -- chemicals and beliefs -- may impose different
chemical pressures on the brain that reset the "temperature." The real
problem, of course, is that no one knows how to fix the hole in the window,
or even where exactly it is. "This is a thousand-piece puzzle with no picture
on the box," sighed Mayberg.

Blackmon, the Washington psychiatrist, said it behooved mental health
clinicians to better integrate the power of biological treatments with the
effects of belief and therapy.

"We would say it's absurd if an internist says, 'I believe in penicillin, so
everyone should get penicillin whether they have cancer or a broken bone," he
said.