title: Dose equivalents of antidepressants: Evidence-based recommendations from randomized controlled trials.
abstract: BACKGROUND
  Dose equivalence of antidepressants is critically important for clinical practice and for research. There are several methods to define and calculate dose equivalence but for antidepressants, only daily defined dose and consensus methods have been applied to date. The purpose of the present study is to examine dose equivalence of antidepressants by a less arbitrary and more systematic method.
  
  
  METHODS
  We used data from all randomized, double-blind, flexible-dose trials comparing fluoxetine or paroxetine as standard drugs with any other active antidepressants as monotherapy in the acute phase treatment of unipolar depression. We calculated the ratio of the mean doses for each study and weighted it by the total sample size to find the weighted mean ratio for each drug, which was then used to define the drug׳s dosage equivalent to fluoxetine 40mg/d.
  
  
  RESULTS
  We included 83 studies (14 131 participants). In the primary analysis, fluoxetine 40mg/day was equivalent to paroxetine dosage of 34.0mg/day, agomelatine 53.2mg/day, amitriptyline, 122.3mg/day, bupropion 348.5mg/day, clomipramine 116.1mg/day, desipramine 196.3mg/day, dothiepin 154.8mg/day, doxepin 140.1mg/day, escitalopram 18.0mg/day, fluvoxamine 143.3mg/day, imipramine 137.2mg/day, lofepramine 250.2mg/day, maprotiline 118.0mg/day, mianserin, 101.1mg/day, mirtazapine 50.9mg/day, moclobemide 575.2mg/day, nefazodone 535.2mg/day, nortriptyline 100.9mg/day, reboxetine 11.5mg/day, sertraline 98.5mg/day, trazodone 401.4mg/day, and venlafaxine 149.4mg/day. Sensitivity analyses corroborated the results except for doxepin.
  
  
  CONCLUSIONS
  The number of studies for some drugs was small. The current method assumes dose response relationship of antidepressants.
  
  
  CONCLUSIONS
  Our findings can be useful for clinicians when they switch antidepressants and for researchers when they compare various antidepressants in their research.
authors.affiliation: Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine/School of Public Health, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hayasaka
authors.affiliation: Department of Public Health and Community Medicine, Section of Psychiatry, University of Verona, Policlinico "G.B.Rossi", Pzz.le L.A. Scuro, 10, Verona 37134, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Purgato
authors.affiliation: Psychiatric Unit, Istituto di Ricovero e Cura a Carattere Scientifico, Centro San Giovanni di Dio, Fatebenefratelli, Brescia, Italy.
authors.forename: Laura R
authors.initials: LR
authors.lastname: Magni
authors.affiliation: Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine/School of Public Health, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ogawa
authors.affiliation: Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine/School of Public Health, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Takeshima
authors.affiliation: Department of Public Health and Community Medicine, Section of Psychiatry, University of Verona, Policlinico "G.B.Rossi", Pzz.le L.A. Scuro, 10, Verona 37134, Italy; Department of Psychiatry, University of Oxford, Oxford, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cipriani
authors.affiliation: Department of Public Health and Community Medicine, Section of Psychiatry, University of Verona, Policlinico "G.B.Rossi", Pzz.le L.A. Scuro, 10, Verona 37134, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Barbui
authors.affiliation: Department of Psychiatry and Psychotherapy, Technische Universität München, Klinikum rechts der Isar, Ismaningerstr. 22, 81675 Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Leucht
authors.affiliation: Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine/School of Public Health, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Toshi A
authors.initials: TA
authors.lastname: Furukawa
mesh_terms: D000328:Adult; D000639:Amitriptyline / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000627:therapeutic use*; D016642:Bupropion / Q000627:therapeutic use; D015283:Citalopram / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D019317:Evidence-Based Medicine; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use; D016666:Fluvoxamine / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D020912:Moclobemide / Q000627:therapeutic use; D009661:Nortriptyline / Q000627:therapeutic use; D017374:Paroxetine / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D020280:Sertraline / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000639:Amitriptyline; D000928:Antidepressive Agents; D016642:Bupropion; D015283:Citalopram; D005473:Fluoxetine; D016666:Fluvoxamine; D020912:Moclobemide; D009661:Nortriptyline; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline
keywords: Antidepressive agents; Dose equivalence; Fluoxetine; Major depression