Rapid decrease in depressive symptoms with an N-methyl-d-aspartate antagonist in ECT-resistant major depression

Prog Neuropsychopharmacol Biol Psychiatry. 2011 Jun 1;35(4):1155-9. doi: 10.1016/j.pnpbp.2011.03.019. Epub 2011 Apr 3.


Background: Ketamine rapidly improves depressive symptoms in patients with treatment-resistant major depressive disorder (MDD) who do not respond to multiple standard antidepressants. However, it remains unknown whether ketamine is equally effective in patients with MDD who previously also did not respond to electroconvulsive therapy (ECT).

Methods: This study compared 17 patients with treatment-resistant MDD who previously did not respond to ECT and 23 patients with treatment-resistant MDD who had not previously received ECT. All subjects received a single open-label infusion of ketamine (0.5 mg/kg). Patients were evaluated using the Montgomery-Asberg Depression Rating Scale (MADRS) at baseline (60 min before the infusion), as well as at 40, 80, 120, and 230 min after infusion.

Results: Depressive symptoms were significantly improved in the ECT-resistant group at 230 minutes with a moderate effect size (p < .001, d = 0.50, 95% C.I.: 0.21-0.80). At 230 minutes, the non-ECT exposed group showed significant improvement with a large effect size (p < .001, d=1.00, 95% C.I.: 0.71-1.29).

Conclusion: Ketamine appears to improve depressive symptoms in patients with MDD who had previously not responded to ECT. These preliminary results encourage further investigation with a larger sample size to determine effectiveness compared to other treatment-resistant patients with MDD.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Intramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Depressive Disorder, Major / drug therapy*
  • Electroconvulsive Therapy*
  • Excitatory Amino Acid Antagonists / administration & dosage
  • Excitatory Amino Acid Antagonists / therapeutic use*
  • Female
  • Humans
  • Injections, Intravenous
  • Ketamine / administration & dosage
  • Ketamine / therapeutic use*
  • Linear Models
  • Male
  • Middle Aged
  • N-Methylaspartate / antagonists & inhibitors*
  • Psychiatric Status Rating Scales
  • Sample Size
  • Socioeconomic Factors
  • Treatment Failure
  • Young Adult


  • Excitatory Amino Acid Antagonists
  • N-Methylaspartate
  • Ketamine