Antidepressant use primes brain for placebo effect

Putting a twist in a run-of-the-mill medication-versus-placebo trial has revealed that prior treatment with antidepressants appears to prime the brain to exhibit a much stronger response to a placebo. The new study, by UCLA researchers, suggests that how the brain responds to antidepressant medication may be influenced by its remembering of past antidepressant exposure.

Aimee Hunter, the study’s lead author, set out to compare real antidepressant medication and placebo treatments – but she also added a twist by separately examining the data for subjects who had never previously taken an antidepressant and those who had.

The researchers based their findings on electroencephalograph measures that focused on the prefrontal cortex, an area of the brain thought to be involved in planning complex cognitive behavior, personality expression, decision-making and moderating social behavior, all things depressed people wrestle with.

The antidepressant medication given during the study appeared to produce slight decreases in prefrontal brain activity, regardless of whether subjects had received prior antidepressant treatment during their lifetime or not. (A decrease in brain activity is not necessarily a bad thing, the researchers note; with depression, too much activity in the brain can be as bad as too little.)

However, the researchers observed striking differences in the power of placebo, depending on subjects’ prior antidepressant use. Subjects who had never been treated with an antidepressant exhibited large increases in prefrontal brain activity during placebo treatment. But those who had used antidepressant medication in the past showed slight decreases in prefrontal activity – brain changes that were indistinguishable from those produced by the actual drug.

“The brain’s response to the placebo pill seems to depend on what happened previously – on whether or not the brain has ever ‘seen’ antidepressant medication before,” explained Hunter. “If it has seen it before, then the brain’s signature ‘antidepressant-exposure’ response shows up.”

The effect, says Hunter, looks conspicuously like a classical conditioning phenomenon, wherein prior exposure to the actual drug may have produced the specific prefrontal brain response and subsequent exposure to the cues and ritual surrounding drug administration came to elicit a similar brain response through conditioning or associative learning.

She concludes that personal treatment history is one of the many factors that influence the overall effects of treatment and that further research is needed to tease out the changes in brain function that are related to prior antidepressant exposure. Her study appears in the journal Neuropsychopharmacology.

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Source: University of California – Los Angeles

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