Antidepressant, mood stabilizing and procognitive effects of very low dose sublingual ketamine in refractory unipolar and bipolar depression

Int J Neuropsychopharmacol. 2013 Oct;16(9):2111-7. doi: 10.1017/S1461145713000485. Epub 2013 May 20.


Intravenous ketamine (0.5 mg/kg) produces robust, rapid and long-lasting antidepressant effects, but is unpractical. Sublingual administration of ketamine renders better bioavailability (~30%) and less conversion to norketamine than oral administration. We evaluated the therapeutic effects and tolerability of very low dose sublingual (VLDS) racemic ketamine (10 mg from a 100 mg/ml solution for 5 min and swallowed), repeatedly administered every 2-3 d or weekly, in 26 out-patients with refractory unipolar or bipolar depression. According to patients' reports, VLDS ketamine produced rapid, clear and sustained effects, improving mood level and stability, cognition and sleep in 20 patients (77%), with only mild and transient light-headedness as a common side-effect (no euphoria, psychotic or dissociative symptoms). Remission remained in some patients after stopping ketamine. Thus, VLDS ketamine may have broad spectrum effects beyond its antidepressant properties, with rapid onset of action, high efficacy, good tolerability and low cost, allowing extended treatment as needed.

MeSH terms

  • Administration, Sublingual
  • Adult
  • Affect / drug effects*
  • Aged
  • Aged, 80 and over
  • Antidepressive Agents / administration & dosage*
  • Antidepressive Agents / adverse effects
  • Bipolar Disorder / diagnosis
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / psychology
  • Cognition / drug effects*
  • Drug Administration Schedule
  • Female
  • Humans
  • Ketamine / administration & dosage*
  • Ketamine / adverse effects
  • Male
  • Middle Aged
  • Sleep / drug effects
  • Time Factors
  • Treatment Outcome
  • Young Adult


  • Antidepressive Agents
  • Ketamine