title: Non response at week 4 as clinically useful indicator for antidepressant combination in major depressive disorder. A sequential RCT.
abstract: We aimed to compare the efficacy and tolerability of mirtazapine versus SSRIs and to assess whether "non-response at week 4" may be a clinical indicator for combining mirtazapine and SSRIs for subsequent treatment. One-hundred fifty-four outpatients with MDD were randomized to receive mirtazapine or SSRIs in step I (4 weeks). Non-responders in step I were randomly assigned to either mirtazapine or SSRIs monotherapy or their combination in step IIa while responders in step I continued the same monotherapy in step IIb for 4 weeks. In step I, mirtazapine showed significantly faster improvement as shown by higher remission rate at week 2 with NNT = 8 compared to SSRIs. Somnolence rate was higher in mirtazapine and nausea rate was higher in SSRIs. In step IIa, combination therapy showed a more favorable time course than SSRIs monotherapy. For subjects taking SSRIs in step I, combination therapy showed significant better improvement in the Hamilton Depression Rating (HAM-D) score both at week 6 (p = 0.006) and 8 (p = 0.013) than SSRIs monotherapy. About 80% of responders at week 4 could reach remission at week 8 and 64% of non-responders could not reach remission at week 8 for patients who continued monotherapy. When mirtazapine was added on for SSRIs non-responders at week 4, the remission rate increased by 5% and HAM-D score improved by 4 points. While for mirtazapine non-responders, SSRIs add-on was not equally effective. Mirtazapine may provide a faster improvement and "non-response at week 4" may be indicator to mirtazapine add-on for patients receiving SSRIs.
authors.affiliation: Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan. Electronic address: katom@takii.kmu.ac.jp.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan.
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Takekita
authors.affiliation: Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Koshikawa
authors.affiliation: Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan.
authors.forename: Shiho
authors.initials: S
authors.lastname: Sakai
authors.affiliation: Seishokai Sephiroth Hospital, Shiga, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Bandou
authors.affiliation: Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Nishida
authors.affiliation: Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan.
authors.forename: Naotaka
authors.initials: N
authors.lastname: Sunada
authors.affiliation: Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Onohara
authors.affiliation: Seishokai Sephiroth Hospital, Shiga, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hatashita
authors.affiliation: Department of Biomedical and NeuroMotor Sciences, University of Bologna, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Serretti
authors.affiliation: Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kinoshita
mesh_terms: D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D000078785:Mirtazapine; D011569:Psychiatric Status Rating Scales; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D008803:Mianserin; D000078785:Mirtazapine; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Antidepressant combination; Major depressive disorder; Mirtazapine; Non response; Randomized controlled trial; SSRI