Pre-treatment plasma cytokine levels as potential predictors of short-term remission of depression

Abstract

Objectives

The response to antidepressants varies significantly among individuals and is difficult to predict before treatment. In this randomised control trial, we explored cytokines that correlate with the therapeutic effect of mirtazapine (MIR) and selective serotonin reuptake inhibitors (SSRIs) and whether they could be predictors of remission for each antidepressant.

Methods

Plasma cytokines, such as tumour necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were assayed in 95 participants before medication and assayed by the enzyme-linked immunosorbent assay. The Hamilton Rating Scale for Depression assessed depressive symptoms over 4 weeks.

Results

In the SSRI group, the baseline GM-CSF level was significantly higher in the remission group than in the non-remission group (p = .022). In the MIR group, the baseline level of TNF-α was significantly higher (p = .039) and IL-2 was lower (p = .032) in the remission group than in the non-remission group. In patients prescribed with MIR, the cut-off values of TNF-α (10.035 pg/mL) and IL-2 (1.170 pg/mL) calculated from the receiver operating characteristic curve suggested that the remission rate, which corresponds to a positive predictive value, could be increased from 31.3% to 60.0% and 50.0%, respectively. For those prescribed with SSRIs, the remission rate was 37.0% and using the cut-off value of GM-CSF (0.205 pg/mL), the remission rate could be almost doubled to 70%.

Conclusions

Our study shows that pre-treatment plasma concentrations of TNF-α, IL-2, and GM-CSF may suggest the predictability of remission by SSRIs or MIR.

Keywords:

• Major depressive disorder
• cytokine
• predictor of remission
• mirtazapine
• selective serotonin reuptake inhibitor

Acknowledgments

We thank Professor Reiji Yoshimura for providing guidance and support and thank all the patients for taking their time for our study.

Statement of interest

We have had the following interests for the past 3 years. Masaki Kato has received grant funding from the Ministry of Health, Labour and Welfare of Japan, the Japan Society for the Promotion of Science, SENSHIN Medical Research Foundation and Japan Research Foundation for Clinical Pharmacology, and speaker’s honoraria from Sumitomo Dainippon Pharma, Otsuka, Meiji-Seika Pharma, Eli Lilly, MSD K.K., GlaxoSmithKline, Pfizer, Janssen Pharmaceutical, Shionogi, Mitsubishi Tanabe Pharma, Takeda Pharmaceutical, Lundbeck and Ono Pharmaceutical. Tadafumi Kato has received grants and personal fees from Japan Agency for Medical Research and Development (AMED), grants and personal fees from Ministry of Education, Culture, Sports, Science and Technology (MEXT)/Japan Society for the Promotion of Science (JSPS), during the conduct of the study; personal fees from Kyowa Hakko Kirin Co., Ltd., personal fees from Eli Lilly Japan K.K., grants and personal fees from Otsuka Pharmaceutical Co., Ltd., personal fees from GlaxoSmithKline K.K., personal fees from Taisho Pharma Co., Ltd., grants and personal fees from Dainippon Sumitomo Pharma Co., Ltd., personal fees from Meiji Seika Pharma Co., Ltd., personal fees from Pfizer Japan Inc., personal fees from Mochida Pharmaceutical Co., Ltd., grants and personal fees from Shionogi & Co., Ltd., personal fees from Janssen Pharmaceutical K.K., personal fees from Janssen Asia Pacific, personal fees from Yoshitomiyakuhin, personal fees from Astellas Pharma Inc., personal fees from Nippon Boehringer Ingelheim Co. Ltd., personal fees from MSD K.K., personal fees from Kyowa Pharmaceutical Industry Co., Ltd., grants and personal fees from Takeda Pharmaceutical Co., Ltd., personal fees from Taisho Pharmaceutical Co., Ltd., personal fees from Taisho Toyama Pharmaceutical Co., Ltd., grants and personal fees from Eisai Co., Ltd., grants and personal fees from Mitsubishi Tanabe Pharma Corporation, grants from Teijin Pharma, outside the submitted work. Hikaru Hori has received speaker’s honoraria from Eisai, Eli Lilly, Janssen, Meiji Seika Pharma, Otsuka, Pfizer, Sumitomo Dainippon Pharma, and Takeda. Yoshiteru Takekita has received grant funding from Japan Society for the Promotion of Science, and speaker’s honoraria from Eisai, MSD K.K., Daiichi-Sankyo, Pfizer, UCB Japan, Novartis and Ono Pharmaceutical. Toshihiko Kinoshita has received speaker’s honoraria from Otsuka, Dainippon-Sumitomo Pharma,Meiji-Seika Pharma, Janssen Pharmaceutical, Eisai, Daiichi-Sankyo, Takeda Pharmaceutical, Lundbeck and Ono Pharmaceutical.

The other authors declare that they have no competing interests.

Additional information

Funding

This study was supported by a Grant-in-Aid for Scientific Research [No. 23591684] to Masaki Kato.