Symptomatology and predictors of antidepressant efficacy in extended responders to a single ketamine infusion

J Affect Disord. 2017 Jan 15:208:560-566. doi: 10.1016/j.jad.2016.10.026. Epub 2016 Oct 26.


Background: Antidepressant response to a single subanesthetic dose infusion of the glutamatergic modulator ketamine is transient in most depressed patients; however, a minority continue to experience an extended response. This study examined depressive symptoms and potential clinical predictors of extended response to ketamine in subjects with mood disorders.

Methods: Subjects were diagnosed with either major depressive disorder (MDD) or bipolar depression. All subjects were treatment-resistant and experiencing a major depressive episode of at least moderate severity. MDD subjects were unmedicated and those with bipolar depression were receiving therapeutic-dose lithium or valproate. All subjects received a single 0.5mg/kg ketamine infusion. Data were collected pre-infusion (baseline) and at days one, 14, and 28 post-infusion.

Results: Twelve of 93 (12.9%) participants continued to meet response criteria (50% reduction in Montgomery-Asberg Depression Rating Scale (MADRS) score) at two weeks. All depressive symptoms assessed by the MADRS were improved at two weeks in ketamine responders except for sleep duration/depth. A positive family history of alcohol use disorder in a first-degree relative (FHP) and greater dissociation during the infusion were associated with better antidepressant response at two weeks. Improved measures of apparent sadness, reported sadness, inability to feel, and difficulty concentrating at day 1 correlated most strongly with antidepressant effects at two weeks.

Limitations: Post-hoc design, small sample size, diagnostic heterogeneity.

Conclusions: Static (FHP) and dynamic (improved depressive symptoms) factors may be clinically useful in predicting whether a patient will have an extended response to ketamine.

Trial registration: NCT00088699.

Keywords: Antidepressant; Bipolar depression; Glutamatergic modulator; Ketamine; Major depressive disorder; NMDA receptor antagonist; Treatment-resistant depression.

Publication types

  • Review

MeSH terms

  • Adult
  • Alcohol-Related Disorders
  • Antidepressive Agents / therapeutic use
  • Bipolar Disorder / drug therapy*
  • Depressive Disorder, Major / drug therapy*
  • Female
  • Humans
  • Infusions, Intravenous
  • Ketamine / administration & dosage*
  • Lithium / therapeutic use
  • Male
  • Middle Aged
  • Psychiatric Status Rating Scales
  • Treatment Outcome
  • Valproic Acid / therapeutic use


  • Antidepressive Agents
  • Valproic Acid
  • Ketamine
  • Lithium

Associated data