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

Naji C. Salloum, Maurizio Fava, Rebecca S. Hock, Marlene P. Freeman, Martina Flynn, Bettina Hoeppner, Cristina Cusin, Dan V. Iosifescu, Madhukar H Trivedi, Gerard Sanacora, Sanjay J. Mathew, Charles Debattista, Dawn F. Ionescu, George I. Papakostas

Research output: Contribution to journalArticle


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.

Original languageEnglish (US)
Pages (from-to)131-139
Number of pages9
JournalJournal of affective disorders
StatePublished - Jan 1 2020



  • Ketamine
  • Major depressive disorder
  • Relapse
  • Remission
  • Treatment-resistant depression

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health

Cite this

Salloum, N. C., Fava, M., Hock, R. S., Freeman, M. P., Flynn, M., Hoeppner, B., Cusin, C., Iosifescu, D. V., Trivedi, M. H., Sanacora, G., Mathew, S. J., Debattista, C., Ionescu, D. F., & Papakostas, G. I. (2020). Time to relapse after a single administration of intravenous ketamine augmentation in unipolar treatment-resistant depression. Journal of affective disorders, 260, 131-139. https://doi.org/10.1016/j.jad.2019.09.017