Targeting Inflammation in Treatment Resistant Depression

Research published in this month’s Archives of General Psychiatry
evaluated the use of a monoclonal antibody (mAb) against tumor necrosis factor (TNF) alpha for treatment resistant depression.

Researchers at Emory University studied whether blocking inflammation would be a useful treatment for either a wide range of people with difficult-to-treat depression or only those with high levels of inflammation. Previous studies have suggested that depressed people with evidence of high inflammation are less likely to respond to traditional treatments for the disorder, such as antidepressants and psychotherapy.

Study participants, 60 medically stable outpatients with a diagnosis of major depression and moderately treatment resistant to conventional antidepressants, were assigned either to monoclonal antibody or to a non-active placebo treatment. Subjects received 3 infusions of the TNF antagonist (n = 30) or placebo (n = 30) at baseline and at week 2 and 6 of a 12-week trial. Results for the group as a whole, showed no significant differences in the improvement of depression symptoms between the drug and placebo groups. However, when the subjects with high inflammation were examined separately, they exhibited a much better response to the mAb than to placebo.

In this study, inflammation was measured using a simple blood test that is readily available in most clinics and hospitals and measures C-reactive protein or CRP. The higher the CRP, the higher the inflammation, and the higher the likelihood of responding to the drug. According to the authors, “the prediction of an antidepressant response using a simple blood test is one of the holy grails in psychiatry. 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.” The researchers also point out that “this is the first successful application of a biologic therapy to depression,” which may open the door to new approaches that target the immune system to treat psychiatric diseases.

Archives of General Psychiatry