Time to relapse after a single administration of intravenous ketamine augmentation in unipolar treatment-resistant depression

J Affect Disord. 2020 Jan 1:260:131-139. doi: 10.1016/j.jad.2019.09.017. Epub 2019 Sep 3.


Objective: To examine the rate and time to relapse for remitters and responders to ketamine in treatment-resistant depression (TRD).

Methods: Subjects with TRD were randomized to a single infusion of one of several doses of intravenous ketamine, or midazolam. Using Kaplan-Meier survival function, the current report examines the rate and time to relapse, defined as MADRS ≥ 22, over a period of 30 days, in subjects who achieved remission (MADRS ≤ 10) or response (≥ 50% reduction in MADRS) on day three post-infusion of intravenous ketamine 0.1, 0.5, or 1.0 mg/kg.

Results: Of the 60 randomized participants who received a single ketamine (0.1, 0.5, or 1.0 mg/kg) infusion, 19 (34%) met criteria for remission and 27 (48%) for response, on day 3 post-infusion. A numerical dose-response relationship was observed, with remitters/responders on ketamine 1.0 mg/kg having the lowest relapse rate, followed by ketamine 0.5 mg/kg and 0.1 mg/kg, respectively (% of remitters who relapsed by day 14: 38% with 1.0 mg/kg, 50% with 0.5 mg/kg, 100% with 0.1 mg/kg;% of responders who relapsed by day 14: 30% with 1.0 mg/kg, 50% with 0.5 mg/kg, 80% with 0.1 mg/kg).

Limitations: The sample size was small. No MADRS measurements at day one post-infusion. The study was not powered to assess differences in relapse prevention between different doses of ketamine.

Conclusion: Time to relapse after successful treatment with a single infusion of ketamine appears to follow a dose-response relationship, where higher dosage leads to increased time to relapse.

Keywords: Ketamine; Major depressive disorder; Relapse; Remission; Treatment-resistant depression.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Depressive Disorder, Major / drug therapy
  • Depressive Disorder, Treatment-Resistant / drug therapy*
  • Female
  • Humans
  • Infusions, Intravenous
  • Ketamine / therapeutic use*
  • Male
  • Middle Aged
  • Random Allocation
  • Recurrence
  • Young Adult


  • Ketamine