title: Selecting among second-step antidepressant medication monotherapies: predictive value of clinical, demographic, or first-step treatment features.
abstract: BACKGROUND
  Little is known about selecting among second-step medications for major depressive disorder after intolerance or lack of remission with an initial selective serotonin reuptake inhibitor.
  
  
  OBJECTIVE
  To determine whether sociodemographic, clinical, or first-step treatment features predict remission with or intolerance overall or differentially to any 1 of 3 second-step medications after an unsatisfactory outcome with citalopram hydrobromide.
  
  
  METHODS
  An equipoise stratified randomized study. Participants were recruited from July 17, 2001, through April 20, 2004.
  
  
  METHODS
  Public or private sector primary care (n = 18) and psychiatric care (n = 23) settings across the United States.
  
  
  METHODS
  Representative outpatients aged 18 to 75 years with nonpsychotic major depressive disorder (N = 727).
  
  
  METHODS
  Sustained-release bupropion hydrochloride was started at 150 mg/d and incrementally increased to 400 mg/d. Sertraline hydrochloride was started at 50 mg/d and incrementally increased to 200 mg/d. Extended-release venlafaxine hydrochloride was started at 37.5 mg/d and incrementally increased to 375 mg/d.
  
  
  METHODS
  The 16-item Quick Inventory of Depressive Symptomatology, Self-Rated and the Frequency, Intensity, and Burden of Side Effects Rating.
  
  
  RESULTS
  Remission was more likely among participants who were white, employed, cohabiting or married, or privately insured or who had prior intolerance to citalopram or at least a response to citalopram, and no prior suicide attempts. Remission was less likely among participants with concurrent generalized anxiety, obsessive-compulsive, panic, or posttraumatic stress disorders; social phobia; anxious or melancholic features; or more severe depression. Intolerance was less likely for Hispanic participants, but more likely for participants with previous suicide attempts or intolerance to citalopram. Participants with concurrent substance use were less likely to remit (odds ratio, 0.37) and more likely not to tolerate extended-release venlafaxine. Intolerance to citalopram was associated with intolerance to sertraline (P = .04).
  
  
  CONCLUSIONS
  Clinical, demographic, and treatment history were of little value in recommending 1 medication vs another as a second-step treatment for major depressive disorder. Participants most likely to remit in the second step had less Axis I psychiatric disorder comorbidity, less social disadvantage, and at least a response to citalopram in the first step.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00021528.
authors.affiliation: Department of Psychiatry, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390, USA. John.Rush@utsouthwestern.edu
authors.forename: A John
authors.initials: AJ
authors.lastname: Rush
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Wisniewski
authors.forename: Diane
authors.initials: D
authors.lastname: Warden
authors.forename: James F
authors.initials: JF
authors.lastname: Luther
authors.forename: Lori L
authors.initials: LL
authors.lastname: Davis
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Nierenberg
authors.forename: Madhukar H
authors.initials: MH
authors.lastname: Trivedi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage* / Q000009:adverse effects; D016642:Bupropion / Q000008:administration & dosage* / Q000009:adverse effects; D015283:Citalopram / Q000008:administration & dosage / Q000009:adverse effects; D003511:Cyclohexanols / Q000008:administration & dosage* / Q000009:adverse effects; D003692:Delayed-Action Preparations; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004351:Drug Resistance; D006801:Humans; D008875:Middle Aged; D010555:Personality Inventory; D011320:Primary Health Care; D011379:Prognosis; D019233:Retreatment; D055502:Secondary Prevention; D020280:Sertraline / Q000008:administration & dosage* / Q000009:adverse effects; D000069470:Venlafaxine Hydrochloride
chemical_list: D018687:Antidepressive Agents, Second-Generation; D003511:Cyclohexanols; D003692:Delayed-Action Preparations; D016642:Bupropion; D015283:Citalopram; D000069470:Venlafaxine Hydrochloride; D020280:Sertraline