title: Placebo-controlled pilot trial testing dose titration and intravenous, intramuscular and subcutaneous routes for ketamine in depression.
abstract: This pilot study assessed the feasibility, efficacy and safety of an individual dose-titration approach, and of the intravenous (IV), intramuscular (IM) and subcutaneous (SC) routes for treating depression with ketamine.
  
  
  
  Fifteen treatment-refractory depressed participants received ketamine or midazolam (control treatment) in a multiple crossover, double-blind study. Ketamine was administered by IV (n = 4), IM (n = 5) or SC (n = 6) injection. Dose titration commenced at 0.1 mg/kg, increasing by 0.1 mg/kg up to 0.5 mg/kg, given in separate treatment sessions separated by ≥1 week, with one placebo control treatment randomly inserted. Mood, psychotomimetic and hemodynamic effects were assessed and plasma ketamine concentrations assayed.
  
  
  
  Twelve participants achieved response and remission criteria, achieved at doses as low as 0.1 mg/kg. All three routes of administration resulted in comparable antidepressant effects. Fewest adverse effects were noted with the SC route. Antidepressant response, adverse effects and ketamine concentrations were dose-related.
  
  
  
  Antidepressant response occurred at a range of doses and at <0.5 mg/kg. The dose-titration approach is a practical method for optimizing the efficacy - side-effects trade-off on an individual patient basis. This pilot study provides preliminary evidence for SC injection as a practical, feasible and efficacious treatment approach.
authors.affiliation: School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.|Black Dog Institute, Randwick, NSW, Australia.|Wesley Hospital, Kogarah, NSW, Australia.|St George Hospital, Kogarah, NSW, Australia.
authors.forename: C K
authors.initials: CK
authors.lastname: Loo
authors.affiliation: School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.|Black Dog Institute, Randwick, NSW, Australia.
authors.forename: V
authors.initials: V
authors.lastname: Gálvez
authors.affiliation: School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
authors.forename: E
authors.initials: E
authors.lastname: O'Keefe
authors.affiliation: School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.|Black Dog Institute, Randwick, NSW, Australia.
authors.forename: P B
authors.initials: PB
authors.lastname: Mitchell
authors.affiliation: School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.|Black Dog Institute, Randwick, NSW, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Hadzi-Pavlovic
authors.affiliation: Wesley Hospital, Kogarah, NSW, Australia.|Royal North Shore Hospital, St Leonards, NSW, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Leyden
authors.affiliation: Wesley Hospital, Kogarah, NSW, Australia.|University of New South Wales, Randwick, NSW, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Harper
authors.affiliation: University of Adelaide, Adelaide, SA, Australia.|Royal Adelaide Hospital, Adelaide, SA, Australia.
authors.forename: A A
authors.initials: AA
authors.lastname: Somogyi
authors.affiliation: Macquarie Hospital, Sydney, NSW, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Lai
authors.affiliation: School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.|Schizophrenia Research Institute, Randwick, NSW, Australia.|Neuroscience Research Australia, Randwick, NSW, Australia.
authors.forename: C S
authors.initials: CS
authors.lastname: Weickert
authors.affiliation: Psychological Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: P
authors.initials: P
authors.lastname: Glue
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage*; D018592:Cross-Over Studies; D003866:Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D007649:Ketamine / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D007649:Ketamine
keywords: dose titration; intramuscular; intranasal; intravenous; ketamine