Continuation phase intravenous ketamine in adults with treatment-resistant depression

J Affect Disord. 2016 Dec;206:300-304. doi: 10.1016/j.jad.2016.09.008. Epub 2016 Sep 12.


Background: Little is known about the antidepressive effects of repeated intravenous ketamine infusions beyond the acute phase of treatment in patients with refractory depression.

Methods: Twelve subjects with treatment-resistant non-psychotic unipolar or bipolar major depression and suicidal ideation were given repeated (up to 6) thrice-weekly acute-phase intravenous infusions of ketamine (0.5mg/kg, administered over 100min). Those who remitted during acute-phase treatment received continuation-phase treatment that consisted of 4 weekly ketamine infusions, followed by 4 weeks of post-continuation phase follow-up (during which no further ketamine infusions were administered). Clinical measures were assessed at baseline, at 24h following each infusion, at the last acute-phase observation, and during continuation and post-continuation follow-up (acute phase remitters only).

Results: Of the 12 enrollees, 5 (41.7%) remitted and 7 (58.3%) responded to ketamine treatment during the acute-phase. All five subjects who remitted during the acute-phase experienced further depressive symptom improvement during continuation-phase treatment. Four subjects lost remission status during the post-continuation phase, but all were still classified as positive treatment responders at the end of the post-continuation phase. Adverse effects were generally mild and transient during acute- and continuation-phase treatment; however, one subject developed behavioral outbursts and suicide threats during follow-up while hospitalized, and one subject died by suicide several weeks after the end of follow-up.

Limitations: This was an uncontrolled feasibility study with a small sample size.

Conclusions: The continuation-phase administration of ketamine at weekly intervals to patients with treatment-resistant depression who remitted during acute-phase ketamine treatment can extend the duration of depressive symptom remission. The antidepressive effect of ketamine persisted for several weeks after the end of continuation-phase treatment. Our results highlight the need for close monitoring of subjects who are at high baseline risk for suicide but do not respond clinically to ketamine. CLINICALTRIALS.

Gov identifier: NCT02094898.

Keywords: Bipolar depression; Continuation; Depression; Ketamine; Major depression; Repeated; Treatment resistant.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Antidepressive Agents / therapeutic use*
  • Bipolar Disorder / drug therapy*
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Treatment-Resistant / drug therapy*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Infusions, Intravenous
  • Ketamine / therapeutic use*
  • Male
  • Middle Aged
  • Remission Induction
  • Sample Size
  • Suicidal Ideation
  • Young Adult


  • Antidepressive Agents
  • Ketamine

Associated data