title: Milnacipran treatment and potential biomarkers in depressed patients following an initial SSRI treatment failure: a prospective, open-label, 24-week study.
abstract: 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: χ (2)=23.9, df=4, P<0.001) only in non-responders.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan ; Sodegaura Satsukidai Hospital, Chiba University, Chiba, Japan.
authors.forename: Tasuku
authors.initials: T
authors.lastname: Hashimoto
authors.affiliation: Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Daiji
authors.initials: D
authors.lastname: Sakurai
authors.affiliation: Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Oda
authors.affiliation: Department of Psychiatry, Chiba University Hospital, Chiba, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hasegawa
authors.affiliation: Division of Medical Treatment and Rehabilitation, Centre for Forensic Mental Health, Chiba University, Chiba, Japan.
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Kanahara
authors.affiliation: Department of Psychiatry, Chiba University Hospital, Chiba, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Department of Psychiatry, Chiba University Hospital, Chiba, Japan ; Choshi Kokoro Clinic, Chiba, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Komatsu
authors.affiliation: Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan ; Choshi Kokoro Clinic, Chiba, Japan.
authors.forename: Junpei
authors.initials: J
authors.lastname: Takahashi
authors.affiliation: Mobara Shinkeika Hospital, Chiba, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Oiwa
authors.affiliation: Division of Medical Treatment and Rehabilitation, Centre for Forensic Mental Health, Chiba University, Chiba, Japan ; Choshi Kokoro Clinic, Chiba, Japan.
authors.forename: Yoshimoto
authors.initials: Y
authors.lastname: Sekine
authors.affiliation: Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan ; Department of Psychiatry, Chiba University Hospital, Chiba, Japan.
authors.forename: Masaomi
authors.initials: M
authors.lastname: Iyo
keywords: adverse effects; biomarkers; cytokines; major depressive disorder; milnacipran