title: Pilot dose-response trial of i.v. ketamine in treatment-resistant depression.
abstract: OBJECTIVE
  Research studies have reported impressive antidepressant effects with ketamine but significant knowledge gaps remain over the best method of administering ketamine, and the relationships between dose, antidepressant response and adverse effects.
  
  
  METHODS
  In this pilot dose-finding study, the efficacy and tolerability of ketamine given by rapid intravenous (i.v.) infusion were assessed in a double-blind, placebo-controlled, crossover design, in four subjects with treatment- resistant depression. Each subject received up to four i.v. doses of ketamine (0.1, 0.2, 0.3, 0.4 mg/kg), given over 2-5 min, 1 week apart, and one randomly inserted placebo treatment.
  
  
  RESULTS
  Three of four subjects achieved antidepressant response (≥ 50% decrease in Montgomery-Asberg Depression Rating Scale scores), two at the minimum 0.1 mg/kg dose, though all relapsed within a week. For two subjects, the greatest improvement occurred at the highest dose received. Rapid infusion over 2 min led to significant adverse psychotomimetic effects which also increased proportionately with ketamine dosage.
  
  
  CONCLUSIONS
  This is the first trial to present dose-response data of ketamine efficacy and psychomimetic effects in depressed subjects. Antidepressant efficacy may be dose-related. Psychotomimetic effects were dose-related. Rapid infusion over 2 min may not be a feasible clinical approach to treatment, given poor tolerability.
authors.affiliation: South Eastern Sydney Local Health District and University of New South Wales , Sydney.
authors.forename: Rosalyn
authors.initials: R
authors.lastname: Lai
authors.forename: Natalie
authors.initials: N
authors.lastname: Katalinic
authors.forename: Paul
authors.initials: P
authors.lastname: Glue
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Somogyi
authors.forename: Philip B
authors.initials: PB
authors.lastname: Mitchell
authors.forename: John
authors.initials: J
authors.lastname: Leyden
authors.forename: Simon
authors.initials: S
authors.lastname: Harper
authors.forename: Colleen K
authors.initials: CK
authors.lastname: Loo
mesh_terms: D000328:Adult; D000368:Aged; D018592:Cross-Over Studies; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007649:Ketamine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine
keywords: depression; dose–response relationship; drug-related side effects and adverse reactions; intravenous administration; ketamine