Placebo, Antidepressant May Lift Depression Via Common Mechanism

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Placebo, Antidepressant May Lift Depression Via Common Mechanism

http://www.nih.gov/news/pr/may2002/nimh-01.htm

Whether it's a widely prescribed medication or a placebo, a successful

treatment for depression must trigger a common pattern of brain activity

changes, suggests a team of researchers funded by the National Institute

of Mental Health.

Using functional brain imaging, Helen Mayberg, M.D., and colleagues at

the University of Texas Health Science Center, San , have found

increased activity in the cortex accompanied by decreases in limbic

regions in patients who responded to either the popular antidepressant

fluoxetine or to a placebo. They propose that this pattern of changes

may be necessary for therapeutic response. However, patients who

responded to fluoxetine also experienced unique changes in lower areas —

brainstem, striatum and hippocampus — thought to confer additional

advantage in sustaining the response long term and preventing relapse.

The researchers report on their Positron Emission Tomography (PET scan)

study in the May 2002 American Journal of Psychiatry.

" Our findings do not support the notion that antidepressants work merely

via a placebo effect, " cautioned Mayberg, who has since moved to the

Rotman Research Institute at the University of Toronto. " Patients on

active medication who failed to improve did not sustain the brainstem,

striatal and hippocampus changes unique to antidepressant responders. "

In the randomized, double blind trial, 17 middle-aged men, hospitalized

for unipolar depression, received either fluoxetine or placebo for 6

weeks. Rating scales revealed that 4 of the men responded to placebo and

another 4 showed comparable improvement with the active medication. Nine

patients failed to get better.

" Treatment with placebo is not absence of treatment, just absence of

active medication, " note the researchers, citing possible therapeutic

benefits of a change in environment and the supportive, therapeutic

milieu of an inpatient psychiatric ward.

PET scans traced the destination of a radioactive form of glucose — the

brain's fuel — to detect brain activity patterns. After 6 weeks, brains

of men who responded to either treatment showed " remarkable

concordance: " Activity increased in prefrontal cortex, posterior

cingulate, premotor, parietal cortex, and posterior insula. Activity

decreased in subgenual cingulate, parahippocampus, thalamus and

hypothalamus.

Men who responded to fluoxetine, in addition, showed changes in certain

lower brain areas — brainstem, hippocampus, striatum and anterior

insula. Brain areas activated in the fluoxetine responders were also

somewhat larger. The brain stem and hippocampus appear to have important

input in sustaining the cortical/limbic changes, suggest the

researchers, who note that absence of changes in these lower brain areas

in placebo responders may render them at higher risk for relapse, which

several previous clinical studies have shown.

Although both placebo and antidepressant responders showed increased

activity in the posterior cingulate (see graphic) at 6 weeks, this

change had already occurred in placebo responders at 1 week. Together

with other evidence, this suggests that the ability to increase activity

in the posterior cingulate may be an early indicator of a brain's

capacity to change and respond to treatment, says Mayberg. Medications

that take a " bottom up " approach or non-drug, cognitive " top-down "

interventions should work equally well. However, a need for

progressively more aggressive treatments could signal " poor adaptive

capacity " in the cortex/limbic network found to change in responders,

say the researchers.