title: Strategic use of new generation antidepressants for depression: SUN(^_^)D study protocol.
abstract: BACKGROUND
  After more than half a century of modern psychopharmacology, with billions of dollars spent on antidepressants annually world-wide, we lack good evidence to guide our everyday decisions in conducting antidepressant treatment of patients with major depression. First we did not know which antidepressant to use as first line treatment. Second we do not know which dosage we should be aiming at with that antidepressant. Because more than half of the patients with major depression starting treatment do not remit after adequate trial with the first agent, they will need a second line treatment. Dose escalation, augmentation and switching are the three often recommended second line strategies but we do not know which is better than the others. Moreover, we do not know when to start considering this second line treatment.The recently published multiple-treatments meta-analysis of 12 new generation antidepressants has provided some partial answers to the first question. Starting with these findings, this proposed trial aims to establish the optimum 1st line and 2nd line antidepressant treatment strategy among adult patients with a non-psychotic unipolar major depressive episode.
  
  
  METHODS
  SUN(^_^)D, the Strategic Use of New generation antidepressants for Depression, is an assessor-blinded, parallel-group, multi-centre randomised controlled trial. Step I is a cluster-randomised trial comparing titration up to the minimum vs maximum of the recommended dose range among patients starting with sertraline. The primary outcome is the change in the Patient Health Questionnaire (PHQ)-9 scores administered by a blinded rater via telephone at week 1 through 3. Step II is an individually randomised trial comparing staying on sertraline, augmentation of sertraline with mirtazapine, and switching to mirtazapine among patients who have not remitted on the first line treatment by week 3. The primary outcome is the change in the PHQ-9 scores at week 4 through 9. Step III represents a continuation phase to Steps I and II and aims to establish longer-term effectiveness and acceptability of the above-examined treatment strategies up to week 25. The trial is supported by the Grant-in-Aid by the Ministry of Health, Labour and Welfare, Japan.
  
  
  CONCLUSIONS
  SUN(^_^)D promises to be a pragmatic large trial to answer important clinical questions that every clinician treating patients with major depression faces in his/her daily practices concerning its first- and second-line treatments.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT01109693.
authors.affiliation: Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine/School of Public Health, Yoshida Konoe-cho, Sakyo-ku, Japan. furukawa@kuhp.kyoto-u.ac.jp
authors.forename: Toshi A
authors.initials: TA
authors.lastname: Furukawa
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Akechi
authors.forename: Shinji
authors.initials: S
authors.lastname: Shimodera
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Yamada
authors.forename: Kazuhira
authors.initials: K
authors.lastname: Miki
authors.forename: Norio
authors.initials: N
authors.lastname: Watanabe
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Inagaki
authors.forename: Naohiro
authors.initials: N
authors.lastname: Yonemoto
mesh_terms: D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage* / Q000009:adverse effects; D016000:Cluster Analysis; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004334:Drug Administration Schedule; D057915:Drug Substitution; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008803:Mianserin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D008875:Middle Aged; D000078785:Mirtazapine; D018579:Patient Selection; D011569:Psychiatric Status Rating Scales; D012107:Research Design; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D020280:Sertraline / Q000008:administration & dosage* / Q000009:adverse effects; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D008803:Mianserin; D000078785:Mirtazapine; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline