A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers.
Level 2 - randomized trial
Double-blind, placebo-controlled randomized trial
PubMed 22945416 · doi:10.1001/2013.jamapsychiatry.4
What was done
A double-blind, placebo-controlled randomized clinical trial in 60 outpatients with treatment-resistant major depression (37 on stable antidepressants, 23 medication-free). Participants received three infusions of infliximab (5 mg/kg, n = 30) or placebo (n = 30) at baseline, week 2, and week 6. Depressive symptoms were tracked over 12 weeks using the 17-item Hamilton Scale for Depression (HAM-D). Baseline inflammatory biomarkers, including high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF), and soluble TNF receptors, were evaluated as predictors of response.
What was found
There was no overall difference in HAM-D score change between infliximab and placebo over time. A significant interaction occurred between treatment, time, and log baseline hs-CRP (P = .01), with infliximab outperforming placebo when baseline hs-CRP was greater than 5 mg/L, and placebo outperforming infliximab when hs-CRP was 5 mg/L or less. In an exploratory subgroup with hs-CRP greater than 5 mg/L, clinical response (≥50% HAM-D reduction) was 62% (8 of 13) for infliximab versus 33% (3 of 9) for placebo (P = .19). Baseline TNF and soluble receptor concentrations were higher in infliximab responders versus nonresponders (P < .05), and infliximab responders had significantly greater decreases in hs-CRP by week 12 than placebo responders (P < .01). Adverse events and dropouts did not differ between groups.
Why it matters
This study provides evidence that anti-inflammatory treatment is not broadly effective for treatment-resistant depression, but may benefit a biologically defined subgroup with elevated peripheral inflammation.
Limits
The overall sample size was small (n = 60), and the biomarker-defined subgroup with hs-CRP greater than 5 mg/L included only 22 patients, leaving subgroup comparisons underpowered. The high-CRP analyses were exploratory, follow-up was limited to 12 weeks, and the cohort was mixed regarding concurrent antidepressant use.
Cited by
- supports Studies have investigated using TNF-alpha blockers as a treatment for depression.