title: Ninety-six hour ketamine infusion with co-administered clonidine for treatment-resistant depression: A pilot randomised controlled trial.
abstract: Objectives We examined the feasibility of a high-dose, 96-h infusion of ketamine in treatment-resistant depression. Methods Ten participants were randomised to receive a 96-h ketamine infusion, titrated as tolerated to a target rate of 0.6 mg/kg/h, while 10 received a 40-min ketamine infusion (0.5 mg/kg). Both groups received clonidine, titrated to a maximum of 0.6 mg orally daily, during the infusion to mitigate side effects of ketamine. Participants were followed for 8 weeks to examine potential antidepressant effects. Results All 20 participants completed the infusion. Most participants tolerated the infusion well, with minimal psychotomimetic symptoms or blood pressure elevation despite achieving high ketamine concentrations (mean 424 ng/ml for 96-h arm, 156 ng/ml for 40-min arm). There was no rebound hypertension upon discontinuing clonidine. Rapid and sustained improvement in depressive symptoms was observed in both study groups. Higher ketamine concentration was associated with sustained antidepressant response, and was not with greater psychotomimetic side effects, in the 96-h arm. Conclusions This study provides evidence for the feasibility of prolonged ketamine infusions in treatment-resistant depression. Co-administration of clonidine appeared to mitigate ketamine's psychotomimetic effects. Further study is required to investigate the extent to which prolonged ketamine infusions could provide both rapid and sustained improvements in treatment-resistant depression. Clinicaltrials.gov identifier NCT01179009.
authors.affiliation: a Washington University School of Medicine , St. Louis , MO 63110 , USA ;
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Lenze
authors.affiliation: a Washington University School of Medicine , St. Louis , MO 63110 , USA ;
authors.forename: Nuri B
authors.initials: NB
authors.lastname: Farber
authors.affiliation: a Washington University School of Medicine , St. Louis , MO 63110 , USA ;
authors.forename: Evan
authors.initials: E
authors.lastname: Kharasch
authors.affiliation: a Washington University School of Medicine , St. Louis , MO 63110 , USA ;
authors.forename: Julie
authors.initials: J
authors.lastname: Schweiger
authors.affiliation: a Washington University School of Medicine , St. Louis , MO 63110 , USA ;
authors.forename: Michael
authors.initials: M
authors.lastname: Yingling
authors.affiliation: a Washington University School of Medicine , St. Louis , MO 63110 , USA ;
authors.forename: John
authors.initials: J
authors.lastname: Olney
authors.affiliation: b Charles E. Schmidt College of Medicine, Florida Atlantic University , Boca Raton , FL 33431 , USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Newcomer
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003000:Clonidine / Q000008:administration & dosage* / Q000009:adverse effects; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007649:Ketamine / Q000008:administration & dosage* / Q000009:adverse effects; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome; D014481:United States
chemical_list: D000928:Antidepressive Agents; D007649:Ketamine; D003000:Clonidine
keywords: Affective disorders; antidepressants; major depressive disorder; psychopharmacology