Effects of Anafranil on Neural Activity at Low Doses

Depression alters how the brain functions on a fundamental level. For example, the depressed brain may have difficulty processing emotions in a logical way. A person with depression may underreact or overreact to stimuli in his or her environment, and some depressed people have no emotional reactions whatsoever, a state of being that psychologists refer to as “flat affect.” Researchers have worked hard to map out the regions of the brain responsible for specific processes. We are beginning to understand how the brain of a depressed person is different from a healthy person’s brain. A study of healthy volunteers in Brazil has provided even more information about both brain function and the activity of the tricyclic antidepressant Anafranil (clomipramine).

The Brazil study recruited 12 nondepressed volunteers with no family history of psychiatric disorders. Each participant was provided a four-week prescription for a low dose of Anafranil. Researchers conducted weekly interviews to ensure that the medication was not having any noticeable effects on the mood states of subjects. The purpose of the research was to study brain changes caused by low doses of Anafranil, independent of mood. In two sessions, one at the end of four weeks with Anafranil and the other after four weeks of “wash out,” subjects were presented with various emotional faces while being scanned with a magnetic resonance imaging (MRI) device. With this technology, researchers were able to pinpoint real-time changes in regional brain activity.

As is often the case in medical science, the results of the study left researchers with as many questions as answers. The amygdalas of study participants showed significant changes during the processing of negative (angry or fearful) emotional faces. Results were less significant for positive (happy) faces. The amygdala is considered responsible for the fight-or-flight fear response and is often overstimulated during depression. Low doses of Anafranil produced a muted amygdala response. Several other regions of the brain also showed changes. After the four-week wash out period, all subjects’ MRI scans revealed a return to baseline activity levels.

This study revealed for the first time that Anafranil may have a clinically significant effect, even at very low doses. Additionally, lower doses equate to fewer adverse side effects. Similar research has suggested that Anafranil at low doses may be just as effective as any of the newer classes of antidepressants, the selective serotonin reuptake inhibitors.

Cardoso de Almeida, J.R., Phillips, M.L., Cerqueira, C.T., Zilberman, M., Lobo, D., Henna, E., et al. (2010). Neural activity changes to emotional stimuli in healthy individuals under chronic use of clomipramine. Journal of Psychopharmacology, 24, (8), 1165-1174.

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