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Milnacipran treatment and potential biomarkers in depressed patients following an initial SSRI treatment failure: a prospective, open-label, 24-week study

Authors Hashimoto T, Sakurai D, Oda Y, Hasegawa T, Kanahara N, Sasaki T, Komatsu H, Takahashi J, Oiwa T, Sekine Y, Watanabe H, Iyo M

Received 25 August 2015

Accepted for publication 9 November 2015

Published 10 December 2015 Volume 2015:11 Pages 3031—3040


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Papan Thaipisuttikul

Peer reviewer comments 2

Editor who approved publication: Professor Wai Kwong Tang

Tasuku Hashimoto,1,2 Daiji Sakurai,1 Yasunori Oda,1 Tadashi Hasegawa,3 Nobuhisa Kanahara,4 Tsuyoshi Sasaki,3 Hideki Komatsu,3,5 Junpei Takahashi,1,5 Takahiro Oiwa,6 Yoshimoto Sekine,4,5 Hiroyuki Watanabe,1 Masaomi Iyo1,3

1Department of Psychiatry, Chiba University Graduate School of Medicine, 2Sodegaura Satsukidai Hospital, 3Department of Psychiatry, Chiba University Hospital, 4Division of Medical Treatment and Rehabilitation, Centre for Forensic Mental Health, Chiba University, 5Choshi Kokoro Clinic, 6Mobara Shinkeika Hospital, Chiba, Japan

Background: We assessed the effect of switching patients with major depressive disorder to milnacipran following an initial selective serotonin reuptake inhibitor treatment failure, and explored potential biomarkers in their blood.
Methods: We conducted a prospective, open-label, 24-week trial. Depression was assessed with the 17-item Hamilton Depression Rating Scale. Patients showing a ≥50% reduction in Hamilton Depression Rating Scale scores from baseline to final visit were considered responders. Regarding adverse effects (AEs), moderate-to-severe AEs were specifically identified as effects that required any medical treatment or that induced treatment withdrawals. We also measured blood levels of various molecules including inflammatory cytokines.
Results: Of the 30 participants who enrolled, 17 completed this study. The responder rate was 30% (n=10). Baseline serum levels of interleukin-6 (Z=-2.155; P=0.031) and interleukin-8 (Z=-2.616; P=0.009) were significantly higher when moderate-to-severe AEs were present (n=13 patients with moderate-to-severe AEs). Serum levels of macrophage inflammatory protein-1β showed a significant continuous decrease from the baseline level (Friedman’s test: χ2=23.9, df=4, P<0.001) only in non-responders.
Conclusion: These results demonstrate that serum levels of interleukin-6, interleukin-8, and macrophage inflammatory protein-1β as potential blood biomarkers could be utilized to identify the responsiveness of patients to serotonin and norepinephrine reuptake inhibitor like milnacipran, or to identify those patients who may experience AEs strong enough to warrant discontinuation of treatment.

Keywords: major depressive disorder, milnacipran, biomarkers, adverse effects, cytokines

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