Plasma Inflammatory Cytokines and Depressed Patients With Comorbid Pain: Improvement by Ketamine

Abstract Background: Depression and pain frequently coexist clinically. Ketamine has analgesic and antidepressant effects, but few studies have evaluated individual differences in antidepressant outcomes to repeated ketamine in depressed patients with comorbid pain. Our aims were to determine the difference in ketamine’s antidepressant effects in depressed patients with or without pain and then to examine whether inflammatory cytokines might contribute to ketamine’s effect. Methods: Seventy-eight patients with major depressive disorder received six infusions of ketamine. Plasma levels of 19 inflammatory cytokines were assessed at baseline and post-infusion (day 13 and day 26) using the Luminex assay. Plasma inflammatory cytokines of sixty healthy controls (HCs) were also examined. Results: At baseline, the levels of GM-CSF, IL-1β and IL-6 were higher in pain group than in non-pain and HC groups. Pain group had better antidepressant outcomes than non-pain group. Pain group showed a greater decrease in IL-6 at day 13 and a greater decrease in IL-10, MIP-3α, IL-1β, IL-5 and IL-6 at day 26 than non-pain group. In the pain group, the changes in IL-6 levels were associated with improvement in pain intensity (β=0.347, t=2.159, P=0.038) and depressive symptoms (β=0.590, t=4.201, P<0.001) at day 13. The Sobel test showed indirect effects between decreases in IL-6 levels and improvement in depressive symptoms (Z=2.026, P=0.043).Conclusion: This study suggested that an elevated inflammatory response plays a key role in individual differences in depressed patients with or without pain. Ketamine showed great antidepressant and analgesic effects in depressed patients with pain, which may be related to its anti-inflammatory effect.