As discussed in chapter 7 of my book, major depressive disorder displays many features that indicate immune involvement. Depressed patients exhibit immune dysregulation, and many of their symptoms resemble those of “sickness behavior”, which is cytokine-driven. Moreover, major depression can by induced in psychologically normal people by injection of certain cytokines. Thus, it is reasonable to ask whether treatment with a known anti-inflammatory agent would alter depressive symptoms. Asdresearchinitiative alerted to me to a small, proof-of-concept stage 4 clinical trial (double-blind, placebo-controlled, randomized) just completed at Emory Medical School that was run by Andy Miller and Charles Raison. This involved periodic intravenous injection of infliximab (Remicade), an antibody that blocks the action of the pro-inflammatory cytokine TNFa. This agent is FDA approved for use in Crohns disease and rheumatoid arthritis, which are conditions with extensive inflammation. Importantly, Miller and colleagues are not only monitoring depressive symptoms and improvement in quality of life, but they are also assaying a blood marker of inflammation, C-Reactive Protein (CRP). (this last test is what is missing in several of the autism treatment trials I’ve discussed here). The patients in this study were resistant to other depression medications.
Aha! A new paper providing the results of this trial has just appeared 2 days ago! Patients who responded to this treatment were those who exhibited elevated CRP at the beginning of the trial. Baseline TNF levels were also higher in the responders than in the non-responders. These results reinforce the point I’ve been making in autism and schizophrenia trials that if one pre-selects patients for a an anti-inflammatory trial that start with elevated inflammatory markers, one is more likely to see a result of the intervention. If the patient pool is diluted with people who aren’t going to respond to the anti-inflammatory agent because they don’t have elevated levels of inflammation to start with, then they will dilute out the results, and investigators will end up with a failed trial and conclude that inflammation is not involved. This Emory trial also indicates that there is diversity among the major depressive disorder population with regard to immune status – which, of course, is also true in autism and schizophrenia. This must be taken into account in planning clinical trials.