A new study suggests that how the brain responds to an antidepressant may be influenced by remembering past antidepressant exposure.
Major depression is typically an event that occurs several times over a lifetime. As a result, an individual may receive multiple courses of antidepressant treatment and researchers wanted to know if the brain may exhibit a “learned” response from prior medication regimens.
Currently, the relationship between prior treatment and the brain’s response to subsequent treatment is unknown.
In the study, researchers used a harmless placebo as the key to tracking the footprints of prior antidepressant use.
Research psychologist Dr. Aimee Hunter worked with UCLA colleagues to demonstrate that a simple placebo pill, made to look like actual medication for depression, can “trick” the brain into responding in the same manner as the actual medication.
The report is found online in the journal European Neuropsychopharmacology.
The investigators examined changes in brain function in 89 depressed persons during eight weeks of treatment, using either an antidepressant medication or a similar-looking placebo pill.
They set out to compare the two treatments — medication versus placebo — but they also added a twist: They separately examined the data for subjects who had never previously taken an antidepressant and those who had.
The researchers 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.
Investigators studied brain changes with electroencephalograph (EEG) measures developed at UCLA by study co-authors Drs. Ian Cook and Andrew Leuchter.
EEG readings are recorded from scalp electrodes and represent the blood flow in the cerebral cortex, which suggests the level of brain activity.
Antidepressant medications 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. Experts say a decrease in brain activity is not necessarily a bad thing as depression is often characterized by too much activity in the brain.
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,” said Hunter. “If it has seen it before, then the brain’s signature ‘antidepressant-exposure’ response shows up.”
According to Hunter, the effect 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 surrounding drug administration — the relationship with the doctor or nurse, the medical treatment setting, the act of taking a prescribed pill and so forth — came to elicit a similar brain response through conditioning or “associative learning.”
The findings suggest that “the behaviors and cues in the environment that are associated with taking medication can come to elicit their own effects. One’s personal treatment history is one of the many factors that influence the overall effects of treatment.”
Still, she noted, there are other possible explanations, and further research is needed to tease out changes in brain function that are related to antidepressant exposure, compared with brain changes that are related to clinical improvement during treatment.