Interesting article

[Guest guest]

Hi all,

Here is an interesting article about sugar pills fighting depression in

studies.

http://www.washingtonpost.com/wp-dyn/articles/A42930-2002May6.html

washingtonpost.com

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. 's wort against

Zoloft. St. '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 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

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 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.

© 2002 The

Washington Post Company