The use of antidepressants to treat depression has increased over the past few decades. Yet, most of the patients do not respond to the treatment or have side effects. This study aims to evaluate how antidepressants act on the brain and neural connectivity. 

This study is included two double-blind, placebo-controlled trials of SNRI antidepressant medications. The first trial comprised duloxetine (30-120 mg daily), and the other comprised desvenlafaxine (50-100 mg daily). The duration of the two trials was 10 and 12 weeks, respectively. The study included a total of 66 participants (32 from duloxetine and 34 from desvenlafaxine). The participants consisted of adults with persistent depressive disorder. The primary outcome was the effect of treatment on whole-brain functional connectivity. 

In both studies, antidepressants decreased functional connectivity within a thalamo-cortico-periaqueductal network, a network that has been previously associated with the experience of pain. The reduction in functional activity in this network equated with improvements in the severity of depressive symptoms in both studies.

The research concluded that the action of antidepressants is associated with decreased functional activity within the thalamo-cortico-periaqueductal network in the brain. This network is also known as the “pain network,” as it is also associated with the experience of pain.