title: Ketamine augmentation for outpatients with treatment-resistant depression: Preliminary evidence for two-step intravenous dose escalation.
abstract: OBJECTIVE
  Preliminary evidence supports the safety and efficacy of subanesthetic ketamine as an experimental antidepressant, although its effects are often not sustained beyond one week. Studies are lacking that have examined the sustained effects of escalating ketamine doses as augmentation in outpatients with treatment-resistant depression. Therefore, the aims of this study were twofold: (1) to assess the safety and antidepressant efficacy of two-step, repeated-dose ketamine augmentation and (2) to assess the duration of ketamine's antidepressant efficacy as augmentation to ongoing antidepressant pharmacotherapy for 3 months after the final infusion.
  
  
  METHODS
  Fourteen patients with treatment-resistant depression were eligible to receive augmentation with six open-label intravenous ketamine infusions over 3 weeks. For the first three infusions, ketamine was administered at a dose of 0.5 mg/kg over 45 minutes; the dose was increased to 0.75 mg/kg over 45 minutes for the subsequent three infusions. The primary outcome measure was response (as measured on Hamilton Depression Rating Scale-28 items).
  
  
  RESULTS
  After the completion of three ketamine infusions, 7.1% (1/14) responded; after all six ketamine infusions, 41.7% (5/12) completers responded and 16.7% (2/12) remitted. Intent-to-treat response and remission rates at the end of the final infusion were 35.7% (5/14) and 14.3% (2/14), respectively. However, all but one responder relapsed within 2 weeks after the final infusion.
  
  
  CONCLUSIONS
  Repeated, escalating doses of intravenous ketamine augmentation were preliminarily found to be feasible, efficacious and well tolerated. Interaction with concomitant medications and elevated level of treatment resistance are possible factors for non-response.
authors.affiliation: 1 Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cusin
authors.affiliation: 1 Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Dawn Flosnik
authors.initials: DF
authors.lastname: Ionescu
authors.affiliation: 1 Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.|2 Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Kara Jean
authors.initials: KJ
authors.lastname: Pavone
authors.affiliation: 2 Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Oluwaseun
authors.initials: O
authors.lastname: Akeju
authors.affiliation: 1 Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Paolo
authors.initials: P
authors.lastname: Cassano
authors.affiliation: 2 Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Norman
authors.initials: N
authors.lastname: Taylor
authors.affiliation: 2 Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Eikermann
authors.affiliation: 1 Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Kelley
authors.initials: K
authors.lastname: Durham
authors.affiliation: 1 Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Michaela Ballentyne
authors.initials: MB
authors.lastname: Swee
authors.affiliation: 1 Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Trina
authors.initials: T
authors.lastname: Chang
authors.affiliation: 1 Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Dording
authors.affiliation: 3 Natividad Medical Center, Salinas, CA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Soskin
authors.affiliation: 1 Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.|4 Department of Psychology, Endicott College, Beverly, MA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Kelley
authors.affiliation: 1 Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Mischoulon
authors.affiliation: 2 Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Emery Neal
authors.initials: EN
authors.lastname: Brown
authors.affiliation: 1 Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007649:Ketamine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D007649:Ketamine
keywords: Major depressive disorder; antidepressant; depression; ketamine; treatment-resistant