Antidepressant SNRI medications reduce connectivity in the brain’s pain network

New research suggests that a brain network associated with the experience of pain could be an important target for antidepressant medications.

The study, published in The Lancet Psychiatry, found that the use of serotonin and norepinephrine reuptake inhibitors (SNRIs) led to changes in the functional architecture of the brain’s pain network.

“We have many treatments in psychiatry that are effective — meaning they are able to reduce symptoms — but we know very little about how they work, or how they change brain function to lead to symptom improvement,” said study author Jonathan Posner, the Suzanne Crosby Murphy Associate Professor of Psychiatry at Columbia University Medical Center.

“The better we can understand how our treatments work, the more closely we can match our patients to the treatment best suited for their condition. We can also use this information to develop new, more targeted treatments that may be more effective with fewer side effects than our existing treatments.”

In two double-blind, placebo-controlled trials of 66 adults with persistent depressive disorder, the researchers found that SNRI antidepressant medications reduced connectivity within the thalamo-cortico-periaqueductal network — a connection of brain regions associated with the processing of pain. The changes in this network were associated with improvements in depressive symptoms.

The researchers used MRI scans to compare brain structure before and after a 10-week trial of duloxetine and 12-week trial of desvenlafaxine.

“Our findings suggest that, at least for some patients with depression, a brain system related to pain (the ‘pain network’) may be an important player in their disorder and interventions that target this brain system might be of particular benefit,” Posner told PsyPost.

“Depression is a heterogeneous disorder, meaning the biological process responsible for depression can differ from one individual to the next. For some depressed individuals, the pain network may play an important role in their depression symptoms, even if they are not describing symptoms of physical pain. For these patients, SNRI antidepressants may be of particular benefit. (SNRI antidepressants are distinct from the more commonly prescribed SSRI antidepressants, such as Prozac and Zoloft.)”

The use of double-blind, placebo-controlled trials allows the researchers to impute causality. But like all research, the study includes some limitations.

“One important caveat is that the change we detected in the pain network was only responsible for part of the treatment effects. In other words, the medications likely cause other brain changes — and these may also be important in helping depressed patients,” Posner explained.

“Another caveat is that although the ‘pain network’ is associated with physical pain, and is named accordingly, this brain system may also underlie painful emotions for some individuals. Pain is a complex psychological state that can be experienced in different ways from one individual to the next.”

Previous research has found that patients with chronic prescription opioid use and depression who adhered to antidepressant medications — including SNRIs — were more likely to stop using opioids.

“Given the opioid crisis in the USA, it is important that we better understand the relationship between pain and depression and how treatments can affect their underlying biology,” Posner said.

“Our findings suggest that SNRI antidepressants offer a treatment that engages the brain’s pain system without being habit forming. This brings up important hypotheses — for instance, might SNRI antidepressants reduce risk for opioid dependence in individuals with chronic pain or depression?”

The study, “The association between antidepressant treatment and brain connectivity in two double-blind, placebo-controlled clinical trials: a treatment mechanism study“, was authored by Yun Wang, Joel Bernanke, Bradley S Peterson, Patrick McGrath, Jonathan Stewart, Ying Chen, Seonjoo Lee , Melanie Wall, Vanessa Bastidas, Susie Hong, Bret R Rutherford, David J Hellerstein, and Jonathan Posner.