title: Single i.v. ketamine augmentation of newly initiated escitalopram for major depression: results from a randomized, placebo-controlled 4-week study.
abstract: BACKGROUND
  While oral antidepressants reach efficacy after weeks, single-dose intravenous (i.v.) ketamine has rapid, yet time-limited antidepressant effects. We aimed to determine the efficacy and safety of single-dose i.v. ketamine augmentation of escitalopram in major depressive disorder (MDD).
  
  
  METHODS
  Thirty outpatients with severe MDD (17-item Hamilton Rating Scale for Depression total score ⩾ 24) were randomized to 4 weeks double-blind treatment with escitalopram 10 mg/day+single-dose i.v. ketamine (0.5 mg/kg over 40 min) or escitalopram 10 mg/day + placebo (0.9% i.v. saline). Depressive symptoms were measured using the Montgomery-Asberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR). Suicidal ideation was evaluated with the QIDS-SR item 12. Adverse psychopathological effects were measured with the Brief Psychiatric Rating Scale (BPRS)-positive symptoms, Young Mania Rating Scale (YMRS) and Clinician Administered Dissociative States Scale (CADSS). Patients were assessed at baseline, 1, 2, 4, 24 and 72 h and 7, 14, 21 and 28 days. Time to response (⩾ 50% MADRS score reduction) was the primary outcome.
  
  
  RESULTS
  By 4 weeks, more escitalopram + ketamine-treated than escitalopram + placebo-treated patients responded (92.3% v. 57.1%, p = 0.04) and remitted (76.9% v. 14.3%, p = 0.001), with significantly shorter time to response [hazard ratio (HR) 0.04, 95% confidence interval (CI) 0.01-0.22, p < 0.001] and remission (HR 0.11, 95% CI 0.02-0.63, p = 0.01). Compared to escitalopram + placebo, escitalopram + ketamine was associated with significantly lower MADRS scores from 2 h to 2 weeks [(peak = 3 days-2 weeks; effect size (ES) = 1.08-1.18)], QIDS-SR scores from 2 h to 2 weeks (maximum ES = 1.27), and QIDS-SR suicidality from 2 to 72 h (maximum ES = 2.24). Only YMRS scores increased significantly with ketamine augmentation (1 and 2 h), without significant BPRS or CADSS elevation.
  
  
  CONCLUSIONS
  Single-dose i.v. ketamine augmentation of escitalopram was safe and effective in severe MDD, holding promise for speeding up early oral antidepressant efficacy.
authors.affiliation: China & Beijing Key Laboratory of Mental Disorders,The National Clinical Research Center for Mental Disorders,Beijing Anding Hospital,Capital Medical University,Beijing,China.
authors.forename: Y-D
authors.initials: YD
authors.lastname: Hu
authors.affiliation: Unit of Psychiatry,Faculty of Health Sciences,University of Macau,Macao SAR,China.
authors.forename: Y-T
authors.initials: YT
authors.lastname: Xiang
authors.affiliation: Unit of Psychological Medicine,Beijing Chao-Yang Hospital,Capital Medical University,Beijing,China.
authors.forename: J-X
authors.initials: JX
authors.lastname: Fang
authors.affiliation: Unit of Psychological Medicine,Beijing Chao-Yang Hospital,Capital Medical University,Beijing,China.
authors.forename: S
authors.initials: S
authors.lastname: Zu
authors.affiliation: China & Beijing Key Laboratory of Mental Disorders,The National Clinical Research Center for Mental Disorders,Beijing Anding Hospital,Capital Medical University,Beijing,China.
authors.forename: S
authors.initials: S
authors.lastname: Sha
authors.affiliation: China & Beijing Key Laboratory of Mental Disorders,The National Clinical Research Center for Mental Disorders,Beijing Anding Hospital,Capital Medical University,Beijing,China.
authors.forename: H
authors.initials: H
authors.lastname: Shi
authors.affiliation: The University of Notre Dame Australia/Marian Centre,Perth,Australia.
authors.forename: G S
authors.initials: GS
authors.lastname: Ungvari
authors.affiliation: Division of Psychiatry Research,The Zucker Hillside Hospital,North Shore-Long Island Jewish Health System,Glen Oaks,NY,USA.
authors.forename: C U
authors.initials: CU
authors.lastname: Correll
authors.affiliation: Department of Psychiatry,Chinese University of Hong Kong,Hong Kong SAR,China.
authors.forename: H F K
authors.initials: HF
authors.lastname: Chiu
authors.affiliation: China & Beijing Key Laboratory of Mental Disorders,The National Clinical Research Center for Mental Disorders,Beijing Anding Hospital,Capital Medical University,Beijing,China.
authors.forename: Y
authors.initials: Y
authors.lastname: Xue
authors.affiliation: China & Beijing Key Laboratory of Mental Disorders,The National Clinical Research Center for Mental Disorders,Beijing Anding Hospital,Capital Medical University,Beijing,China.
authors.forename: T-F
authors.initials: TF
authors.lastname: Tian
authors.affiliation: Unit of Psychological Medicine,Beijing Chao-Yang Hospital,Capital Medical University,Beijing,China.
authors.forename: A-S
authors.initials: AS
authors.lastname: Wu
authors.affiliation: China & Beijing Key Laboratory of Mental Disorders,The National Clinical Research Center for Mental Disorders,Beijing Anding Hospital,Capital Medical University,Beijing,China.
authors.forename: X
authors.initials: X
authors.lastname: Ma
authors.affiliation: China & Beijing Key Laboratory of Mental Disorders,The National Clinical Research Center for Mental Disorders,Beijing Anding Hospital,Capital Medical University,Beijing,China.
authors.forename: G
authors.initials: G
authors.lastname: Wang
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002681:China; D015283:Citalopram / Q000008:administration & dosage* / Q000009:adverse effects; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007649:Ketamine / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010045:Outpatients; D010555:Personality Inventory; D016016:Proportional Hazards Models; D011569:Psychiatric Status Rating Scales; D057566:Self Report; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D015283:Citalopram; D007649:Ketamine
keywords: Efficacy; escitalopram; ketamine; major depression; response; tolerability