PS103. Search for biomarkers for ketamine response from changes of cytokines in the patients with treatment resistant depression Free

Abstract

Objective: Increased levels of pro-inflammatory cytokines were reported to be associated with depression. The aim of this study is to search for biomarker for ketamine antidepressant response using levels of cytokines to account for and predict clinical response.

Methods: we conducted a randomized, double-blind placebo-controlled study comparing the two single subanesthetic doses of ketamine infusion (0.5mg/kg & 0.2mg/kg) vs. placebo (PBO) to see the primary behavioral outcome and the alterations of cytokines level for the secondary outcome. The levels of cytokines such as CRP, IL2, IL6, TNF α measured at baseline, 240 mins, D2 (48 hrs), and D6 with concommitant mood ratings (HAMD-17 and MADRS) and their changes from baseline were assessed and correlated.

Results: Repeated- Measure ANOVA showed no significant differences of group effect on these four-cytokine levels (p=NS) but with significant time effect on IL2, IL6, TNF α. (p=0.034, 0.001 & 0.004 respectively). In that, we observed minimal decreasing rate from baseline to 40 mins and 240 mins post-infusion in IL2 and IL6 (< 5%) while moderate decreasing in TNF α (10–15%). However, no correlations between decreasing rate of cytokines with mood improvemnt rate nor predictors of baseline or changes of cytokines for responder rate (>=50% reduction of either HAMD-17 and MADRS from D2 to D4) were found. Nevertheless, If we divided the cytokine levels using median No into high and low level group, only baseline IL6 high level group (IL6 > 28953pg/ml) and CRP low level group (CRP< <518ng/ml) showed better response in 0.5mg/kg than PBO groups (OR=8.9, CI1.2–20.2 and OR=10.3, CI 1.3–86.5, ps<0.05, respectively).

Conclusion: the results did not find significant biomarkers to predict better respons to 0.5mg/kg ketamine but baseline high IL6 and low CRP level may possible do. Moderate reduction of TNF α level with 0.5mg/kg ketamine might be related to initial antiinflammtory effect.