title: Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial.
abstract: OBJECTIVE
  Ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, has shown rapid antidepressant effects, but small study groups and inadequate control conditions in prior studies have precluded a definitive conclusion. The authors evaluated the rapid antidepressant efficacy of ketamine in a large group of patients with treatment-resistant major depression.
  
  
  METHODS
  This was a two-site, parallel-arm, randomized controlled trial of a single infusion of ketamine compared to an active placebo control condition, the anesthetic midazolam. Patients with treatment-resistant major depression experiencing a major depressive episode were randomly assigned under double-blind conditions to receive a single intravenous infusion of ketamine or midazolam in a 2:1 ratio (N=73). The primary outcome was change in depression severity 24 hours after drug administration, as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS).
  
  
  RESULTS
  The ketamine group had greater improvement in the MADRS score than the midazolam group 24 hours after treatment. After adjustment for baseline scores and site, the MADRS score was lower in the ketamine group than in the midazolam group by 7.95 points (95% confidence interval [CI], 3.20 to 12.71). The likelihood of response at 24 hours was greater with ketamine than with midazolam (odds ratio, 2.18; 95% CI, 1.21 to 4.14), with response rates of 64% and 28%, respectively.
  
  
  CONCLUSIONS
  Ketamine demonstrated rapid antidepressant effects in an optimized study design, further supporting NMDA receptor modulation as a novel mechanism for accelerated improvement in severe and chronic forms of depression. More information on response durability and safety is required before implementation in clinical practice.
authors: James W
authors: JW
authors: Murrough
authors: Dan V
authors: DV
authors: Iosifescu
authors: Lee C
authors: LC
authors: Chang
authors: Rayan K
authors: RK
authors: Al Jurdi
authors: Charles E
authors: CE
authors: Green
authors: Andrew M
authors: AM
authors: Perez
authors: Syed
authors: S
authors: Iqbal
authors: Sarah
authors: S
authors: Pillemer
authors: Alexandra
authors: A
authors: Foulkes
authors: Asim
authors: A
authors: Shah
authors: Dennis S
authors: DS
authors: Charney
authors: Sanjay J
authors: SJ
authors: Mathew
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D061218:Depressive Disorder, Treatment-Resistant / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D007649:Ketamine / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010555:Personality Inventory / Q000706:statistics & numerical data; D011594:Psychometrics
chemical_list: D000928:Antidepressive Agents; D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine
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