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Connectivity of Brain Pain Networks Changes With Antidepressant Treatment

July 18, 2019

By Will Boggs MD

NEW YORK—The functional connectivity of brain networks associated with the experience of pain changes with antidepressant treatment of adults with persistent depressive disorder, researchers report.

"It was interesting to learn that an important driver underlying how antidepressants work is through the brain's pain network - a collection of brain regions that activate together when an individual experiences physical pain," said Dr. Jonathan Posner from New York State Psychiatric Institute and Columbia University College of Physicians and Surgeons, in New York.

"We were treating patients with depression, who were not necessarily experiencing physical pain, and yet we found that it was by lowering connectivity, and presumably activity, within this pain network that antidepressants reduced depressive symptoms," he told Reuters Health by email. "Prior to this study, the pain network had not been recognized as an important factor in treating depression."

For their study, online June 24 in The Lancet Psychiatry, Dr. Posner and colleagues used data from 66 patients who had participated in one of two randomized trial (duloxetine vs. placebo and desvenlafaxine vs. placebo) and had undergone MRI before and after treatment.

In both studies, 18 connectivity clusters were significantly associated with antidepressant treatment, with the greatest similarities in pain networks. Pain-network density did not differ between the groups before treatment, but both drugs were associated with significant decreases in pain-network density compared with placebo.

After controlling for age and sex, improvement in pain symptoms was associated with change in pain-network density in both studies. This association was significant for the active-treatment group of the desvenlafaxine study, but not for the active treatment group of the duloxetine study or for the placebo group of either study.

Overall, improvement in symptoms of depression was not associated with change in pain-network density, but within the active-treatment groups, improvement in depression symptoms was associated with decreases in pain-network density.

In contrast, a worsening of depression symptoms was associated with decreases in pain-network density within the placebo group of the duloxetine study (but not in the desvenlafaxine study).

"The findings suggest that, at least for some patients with depression, the pain network may be an important player in their disorder and interventions that target this network might be of particular benefit," Dr. Posner said. "We have many treatments in psychiatry that are effective, but we still know very little about how they work - how they change brain function to lead to symptom improvement. 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."

"This work is one of the few studies to examine the correlation between response to antidepressant treatment and the effects on brain functional connectivity," write Dr. Yvette I. Sheline and Dr. Meichen Yu from the University of Pennsylvania Perelman School of Medicine, in Philadelphia, in a linked editorial. "The findings of this study - if replicated - suggest that pain network connectivity might provide an important target for new antidepressant therapeutics."

Dr. Esteban Gudayol-Ferre from Universidad Michoacana de San Nicolas de Hidalgo Morelia, in Mexico, who earlier reviewed changes in brain connectivity related to the treatment of depression, told Reuters Health by email, "This result is surprising, but a recent study showed a direct relationships between current depressive symptoms and several variables that included pain conditions. This may explain at least in part why the changes in 'the pain network' after antidepressant treatment may be associated with general improvement in depressive symptoms."

"However," he said, "more studies will be needed to confirm this association because this finding is novel and counterintuitive, since the current literature had suggested that different clusters of symptoms in depression are associated with specific brain networks."

Eli Lilly and Company and Pfizer Pharmaceuticals funded the clinical trials and had various relationships with two of the 13 authors of the new report.


Lancet Psychiatry 2019.

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