Depressed brain can be `primed'

[Guest guest]

Depressed brain can be `primed'

By Brink, Times Staff Writer

August 7, 2006

http://www.latimes.com/features/health/la-he-

depressed7aug07,1,3510494.story

Before the antidepressant ever gets swallowed, before it dissolves

and makes its way through the bloodstream and deep within the gray

matter of the brain, some depressed patients start feeling better

because they think they will. Experiments have shown that healing

from depression starts in some people, called placebo responders,

even when the drug given is just a sugar pill.

That, of course, is not enough to completely cure depression. But if

a placebo can trick the brain into starting to get better, it's

actually a pretty good predictor of who will continue to improve with

antidepressant treatment.

A new study released last week in the American Journal of Psychiatry

shows that the placebo effect may provide a head start for actual

drug treatment by beginning to change the brain pathways that

antidepressants will then follow.

The finding is an important step in helping scientists further refine

who might be helped by drugs and what other factors might be involved

in helping depressed patients get better.

The setting most likely matters too. Feeling free to talk openly

about how he felt, along with a belief that he was going to be

helped, set Chuck Park, 32, of Culver City on a path to healing. He

was a participant in the 51-person study and one of 26 volunteers who

received a placebo for the entire nine weeks of the trial. Another 25

volunteers received antidepressants for eight of the nine

weeks. " After a few weeks, I started to feel a little better, " he

says. " The nurse, , would ask me how I was feeling, and I

knew it wasn't just a superficial question. I could really tell her. "

Activity measured by electroencephalogram in an area of the brain

that is especially active in depressed patients, called the

dorsolateral prefrontal cortex, slows down in some people shortly

after they begin getting a placebo. The slowdown is not enough to

overcome depression, but those people whose brains responded to sugar

pills ended up also responding to antidepressants in the new study.

And Park, who improved slightly on a placebo, saw his depression lift

completely after the trial ended and he started taking

antidepressants.

" It's a very dramatic and clear example demonstrating that medication

itself isn't the whole story, " says Aimee M. Hunter, UCLA

psychologist and lead author of the study. " If there is an actual

formula or recipe for getting better, it may include medication, but

it's very clear that it includes other factors or ingredients. "

The placebo response, as the study measured it, appears to be a

significant ingredient. Researchers attributed about 19% of the mood

improvements measured on a depression scale after the trial to the

placebo effect.

Psychiatric research is different from other kinds of medical

research in that almost all depressed patients are given a placebo

for about a week before the trial starts. Called the placebo lead-in,

it is done to clear the body of other medications the patient might

have been taking, but it is also done to get people used to filling

out forms measuring their feelings and to allow them to meet the

doctors and nurses who will be working with them. " Psychiatric

studies are a lot more personal, " says Dr. Leuchter, director

of the laboratory of brain, behavior and pharmacology at UCLA.

" This is the first study to look at succession, " Leuchter

says. " There are brain changes due to placebo, and changes due to the

medication. "

But that still leaves 81% of the formula predicting treatment success

yet to be sorted out. A patient's beliefs, hopes, expectations and

relationship with the doctor might also play a role.

Leuchter is part of a team of researchers in 10 centers throughout

the country who are beginning to further sort out the elements that

go into treating depression. They will study 300 patients to see if

they can use similar EEG testing to predict which patients will do

well on specific antidepressants.

There are about 20 antidepressants available by prescription, and

patients can fail on several before finding one that works. In fact,

a National Institute of Mental Health sponsored study of 4,000

patients found that only about half of depressed patients got relief

from their symptoms following a first round of treatment with either

an antidepressant or talk therapy.

" Right now, trial and error is the rule, and it can take months to

find the right medication, " says Leuchter.

The new study he's involved with, called the Biomarkers for Rapid

Identification of Treatment Effective in Major Depression trial, will

look at brain changes following one week of treatment with any one of

a number of antidepressants. That won't be enough time for the drugs

to work clinically, but researchers will be looking for early brain

changes. Volunteers will again be tested with EEGs after about three

months of treatment. " We can look at early EEG changes to see if any

of those changes predict how they did later, " he says.

If early brain changes can alert physicians to patients who are on

the right track for treatment, Leuchter says, it could cut down on

the time needed to find the right drug for the right patient. " We're

hoping that within three years, this might be a test available in

doctors' offices, " he says.

It's not just the right drug, either, that has yet to be sorted out.

Depression is complicated and the NIMH is conducting a seven-year

study, called the Sequenced Treatment Alternatives to Relieve

Depression, to determine the effectiveness of various treatments,

including drugs and psychotherapy and combinations of both.

" We know from other studies that psychotherapy also causes certain

brain changes, " Leuchter says. " I believe that engagement with

physicians and attention is a form of supportive therapy. "

It could be, he says, that just as drugs, placebo and talk therapy

can change the brain's circuitry, so can wanting to get better,

believing one will get better, or hearing a physician say there is

great hope that you'll get better.