title: Effect of mirtazapine versus selective serotonin reuptake inhibitors on benzodiazepine use in patients with major depressive disorder: a pragmatic, multicenter, open-label, randomized, active-controlled, 24-week trial.
abstract: BACKGROUND
  This study aimed to evaluate whether selecting mirtazapine as the first choice for current depressive episode instead of selective serotonin reuptake inhibitors (SSRIs) reduces benzodiazepine use in patients with major depressive disorder (MDD). We concurrently examined the relationship between clinical responses and serum mature brain-derived neurotrophic factor (BDNF) and its precursor, proBDNF.
  
  
  METHODS
  We conducted an open-label randomized trial in routine psychiatric practice settings. Seventy-seven MDD outpatients were randomly assigned to the mirtazapine or predetermined SSRIs groups, and investigators arbitrarily selected sertraline or paroxetine. The primary outcome was the proportion of benzodiazepine users at weeks 6, 12, and 24 between the groups. We defined patients showing a ≥50 % reduction in Hamilton depression rating scale (HDRS) scores from baseline as responders. Blood samples were collected at baseline, weeks 6, 12, and 24.
  
  
  RESULTS
  Sixty-five patients prescribed benzodiazepines from prescription day 1 were analyzed for the primary outcome. The percentage of benzodiazepine users was significantly lower in the mirtazapine than in the SSRIs group at weeks 6, 12, and 24 (21.4 vs. 81.8 %; 11.1 vs. 85.7 %, bothP< 0.001; and 12.5 vs. 81.8 %,P= 0.0011, respectively). No between-group difference was observed in HDRS score changes. Serum proBDNF levels were significantly decreased (χ2= 8.5,df= 3,P= 0.036) and serum mature BDNF levels were temporarily significantly decreased (F= 3.5,df= 2.4,P= 0.027) in the responders of both groups at week 24.
  
  
  CONCLUSIONS
  This study demonstrated mirtazapine as the first-choice antidepressant for current depressive episodes may reduce benzodiazepine use in patients with MDD.Trial registrationUMIN000004144. Registered 2nd September 2010. The date of enrolment of the first participant to the trial was 24th August 2010. This study was retrospectively registered 9 days after the first participant was enrolled.
authors: Department of Psychiatry, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670 Japan ; Sodegaura Satsukidai Hospital, 5-21 Nagauraekimae, Sodegaura-shi, 299-0246 Japan.
authors: Tasuku
authors: T
authors: Hashimoto
authors: Department of Psychiatry, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba, 260-0856 Japan ; Kokoronokenko Tsudanuma Clinic, 2-13-13 Maebaranishi, Funabashi-shi, Chiba, 274-0825 Japan.
authors: Akihiro
authors: A
authors: Shiina
authors: Department of Psychiatry, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba, 260-0856 Japan ; Kokoronokenko Tsudanuma Clinic, 2-13-13 Maebaranishi, Funabashi-shi, Chiba, 274-0825 Japan.
authors: Tadashi
authors: T
authors: Hasegawa
authors: Department of Psychiatry, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670 Japan ; Kokoronokaze Funabashi Clinic, 1-26-2 Motomachi, Funabashi-shi, Chiba, 273-0005 Japan.
authors: Hiroshi
authors: H
authors: Kimura
authors: Department of Psychiatry, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670 Japan.
authors: Yasunori
authors: Y
authors: Oda
authors: Department of Psychiatry, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670 Japan ; Fujita Hospital, 3292-Ho Yokaichiba, Sosa-shi, Chiba, 289-2146 Japan.
authors: Tomihisa
authors: T
authors: Niitsu
authors: Department of Psychiatry, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670 Japan.
authors: Masatomo
authors: M
authors: Ishikawa
authors: Fujita Hospital, 3292-Ho Yokaichiba, Sosa-shi, Chiba, 289-2146 Japan.
authors: Masumi
authors: M
authors: Tachibana
authors: Kimura Hospital, 6-19 Higashihoncho, Chuo-ku, Chiba, 260-0004 Japan.
authors: Katsumasa
authors: K
authors: Muneoka
authors: Research Center for Child Mental Development, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670 Japan ; Kisarazu Hospital, 2-3-1 Iwane, Kisarazu-shi, Chiba, 292-0061 Japan.
authors: Satoshi
authors: S
authors: Matsuki
authors: Research Center for Child Mental Development, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670 Japan ; Kokoronokaze Funabashi Clinic, 1-26-2 Motomachi, Funabashi-shi, Chiba, 273-0005 Japan.
authors: Michiko
authors: M
authors: Nakazato
authors: Department of Psychiatry, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670 Japan.
authors: Masaomi
authors: M
authors: Iyo
keywords: Benzodiazepines; Brain-derived neurotrophic factor; Depression; Mirtazapine; Serum