September 12, 2012

Inflammation and Depression: Improving
Therapy Response in Some Patients

Atlanta—Pharmacists see it all the time: patients constantly are trying new medications or combinations of medications to treat their depression, with little success. New research suggests that one possible solution is adding yet another therapy—a drug to control inflammation.

In a new study, investigators from Emory University in Atlanta found that infliximab, commonly used to treat autoimmune and inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease, offers some promise for patients with difficult-to-treat depression.

A possible explanation, according to Andrew H. Miller, MD, senior author for the study and professor of psychiatry and behavioral sciences at Emory University School of Medicine, is that “when prolonged or excessive, inflammation can damage many parts of the body, including the brain.”

According to the study, published September 3rd in the online version of Archives of General Psychiatry, previous research has suggested that high inflammation levels are linked to lower responses to traditional treatments for depression, including psychotherapy and medications.

The study group included a total of 60 outpatients with major depression who were moderately resistant to treatment. The test group of 30 patients was given three 5-mg/kg infusions of the tumor necrosis factor (TNF) antagonist infliximab during the 12-week trial, while the control group, an equal number, was given placebo.

No significant differences in treatment response were noted when investigators looked at the results for the group as a whole, but study participants with high inflammation levels—defined as a baseline hs-CRP concentration greater than 5 mg/L—exhibited a much better response with infliximab treatment.

Treatment response, i.e., a 50% or greater reduction in the Hamilton Rating Scale for Depression (HAM-D) score at any point during treatment, was 62% in infliximab-treated patients versus 33% in placebo-treated patients, according to the study.

“Baseline concentrations of TNF and its soluble receptors were significantly higher in infliximab-treated responders vs. nonresponders (P < .05), and infliximab-treated responders exhibited significantly greater decreases in hs-CRP from baseline to week 12 compared with placebo-treated responders (P < .01),” according to the report.

While the proof-of-concept study suggests that TNF antagonists do not have a generalized positive effect in treatment-resistant depression, they can improve depressive symptoms in patients with high baseline inflammatory biomarkers, according to the authors, who added that the results could have significant implications for treatment of depression in the future.

“The prediction of an antidepressant response using a simple blood test is one of the holy grails in psychiatry,” Miller pointed out. “This is especially important because the blood test not only measured what we think is at the root cause of depression in these patients, but also is the target of the drug.”

“This is the first successful application of a biologic therapy to depression,” noted first author Charles L. Raison, MD, formerly at Emory University but now associate professor in the Department of Psychiatry at the University of Arizona College of Medicine–Tucson. “The study opens the door to a host of new approaches that target the immune system to treat psychiatric diseases.”

U.S. Pharmacist Social Connect