Abstract
Signs of an inflammatory process have been described in major depression. In a double-blind, randomized study of celecoxib or placebo add-on to reboxetine in 40 depressed patients, celecoxib treatment has beneficial effects. In order to evaluate the tryptophan/kynurenine metabolism and to identify predictors for remission, tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QUIN) were estimated in the serum of 32 patients before and after treatment and in a group of 20 healthy controls. KYN levels were significantly lower in patients (p = 0.008), and the QUIN/KYN ratios were significantly higher (p = 0.028). At baseline, the higher KYN/TRP ratio was predictive for remission during celecoxib add-on treatment (p = 0.04) as well as for remission in the overall patient group (p = 0.01). In the placebo group, remitters showed a higher KYNA/QUIN ratio (p = 0.032). In the overall group, remitters showed lower KYNA/KYN (p = 0.035) and QUIN/KYN (p = 0.011) ratios. The lower the formation of downstream metabolites, especially QUIN, the better the treatment outcome. The high KYN/TRP ratio predicted remission after treatment with celecoxib in this small sample of depressed patients. Eventually, the KYN/TRP ratio might be a marker for those patients, which benefit from an additional anti-inflammatory treatment.
Highlights
Activation of the inflammatory response system in major depression (MD) is well documented [1,2,3,4,5]
In the linear regression analysis, the baseline elevated KYN to TRP ratio (KYN/TRP) ratio was predictive for remission to celecoxib add-on treatment in terms of the percentage of patients showing a decrease in HAMD score to 7 or less at the end of the study (B = 0.03, CI = 0.001–0.059, p = 0.04)
Our results show that initial serum kynurenine levels predict remission after add-on treatment with the COX-2 inhibitor celecoxib
Summary
Activation of the inflammatory response system in major depression (MD) is well documented [1,2,3,4,5]. Recent meta-analyses clearly showed elevated interleukin-6 (IL-6) levels in patients with MD [6,7,8,9]. The COX-2 inhibitor celecoxib, an add-on to different antidepressants, has demonstrated beneficial effects in the treatment of depression [15, 16]. Side effects, including cardiovascular effects, have been observed during the use of COX-2 inhibitors, in long-term treatment. With these specific side effects of celecoxib, screening and monitoring for cardiovascular risk factors and events is important, when treating MD with COX-2 inhibitors. A recent meta-analysis with a total of 150 patients has shown that the adjunctive celecoxib group had better remission and response rates than the placebo group [17]. Signs of an inflammatory process have been described in major depression
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