Preprint Article Version 1 This version is not peer-reviewed

Ketoprofen as an Add-on Treatment to Sertraline for Drug-Naïve Major Depressed Patients: Normalization of Plasma Levels of Indoleamine-2,3-Dioxygenase in Association with Pro-Inflammatory and Immune Regulatory Cytokines

Version 1 : Received: 10 December 2018 / Approved: 11 December 2018 / Online: 11 December 2018 (13:52:50 CET)

How to cite: Al-Hakeim, H.; Twayej , A.J..; Al-Dujaili , A.H..; Maes, M. Ketoprofen as an Add-on Treatment to Sertraline for Drug-Naïve Major Depressed Patients: Normalization of Plasma Levels of Indoleamine-2,3-Dioxygenase in Association with Pro-Inflammatory and Immune Regulatory Cytokines. Preprints 2018, 2018120131 (doi: 10.20944/preprints201812.0131.v1). Al-Hakeim, H.; Twayej , A.J..; Al-Dujaili , A.H..; Maes, M. Ketoprofen as an Add-on Treatment to Sertraline for Drug-Naïve Major Depressed Patients: Normalization of Plasma Levels of Indoleamine-2,3-Dioxygenase in Association with Pro-Inflammatory and Immune Regulatory Cytokines. Preprints 2018, 2018120131 (doi: 10.20944/preprints201812.0131.v1).

Abstract

Major Depression Disorder (MDD) is accompanied by an immune response characterized by increased levels of pro-inflammatory and immune-regulatory cytokines and cytokine-induced stimulation of indoleamine-2,3-dioxygenase (IDO). There is also some evidence that anti-inflammatory drugs may have a clinical efficacy in MDD.The aim of this study is to examine the clinical effects of an eight-week combinatorial treatment of ketoprofen (a nonsteroidal anti-inflammatory drug) combined or not with sertraline, on serum levels of IDO, interferon (IFN)-γ, interleukin (IL)-4 and transforming growth factor (TGF)-β1 in association with changes in the Beck-Depression Inventory-II (BDI-II). The study included 140 MDD patients and 40 normal controls. The pre-treatment serum levels of IDO, IFN-γ, TGF-β1 and IL-4 were significantly higher in MDD patients compared with the control group. Treatment with sertraline with or without ketoprofen significantly reduced the increased baseline production of all 4 biomarkers to levels which were similar as those of normal controls. Ketoprofen add-on had a significantly greater effect on IDO and BDI-II as compared with placebo. The reductions in IDO, IL-4 and TGF-β1 during treatment were significantly associated with those in the BDI-II.In conclusion, the clinical efficacy of both sertraline + ketoprofen may be ascribed at least in part to attenuated IDO levels and immune-inflammatory responses in MDD. Moreover, add-on treatment with ketoprofen may augment the efficacy of sertraline by attenuating IDO. However, these treatments may also significantly reduce the more beneficial properties of T helper-2 and T regulatory (Treg) immune subsets. Future research should develop immune treatments that target the immune-inflammatory response in MDD, while enhancing the compensatory immune-regulatory system (CIRS).

Subject Areas

Major depressive disorder (MDD), ketoprofen, TGF-β1, INF-γ, IDO, immune, inflammation

Readers' Comments and Ratings (0)

Leave a public comment
Send a private comment to the author(s)
Rate this article
Views 0
Downloads 0
Comments 0
Metrics 0
Leave a public comment

×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.