Sex differences in response to ketamine as a rapidly acting intervention for treatment resistant depression

Marlene P. Freeman, George I. Papakostas, Bettina Hoeppner, Erica Mazzone, Heidi Judge, Cristina Cusin, Sanjay Mathew, Gerard Sanacora, Dan Iosifescu, Charles DeBattista, Madhukar H. Trivedi, Maurizio Fava

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


Background: While ketamine has been increasingly studied for treatment resistant depression (TRD), the impact of sex differences on treatment outcomes has not been well studied. The objective was to ascertain whether there were differences in response to a single administration of ketamine for TRD between men and women, and between pre- and post-menopausal women. Methods: A randomized, double-blind, placebo-controlled trial (N = 99; N = 50 male; N = 49 female) was conducted to investigate the efficacy of intravenous ketamine versus active placebo as augmentation of antidepressant therapy for TRD. Patients were assigned to one of five arms; one-time administration of ketamine of varying doses (i.e., 0.1, 0.2, 0.5, and 1.0 mg/kg), and one group receiving active placebo (intravenous midazolam). A priori-planned analyses were conducted to compare responses between women and men, as well pre-vs. postmenopausal women. Results: Analyses demonstrated no significant differences between women and men in terms of treatment response (F(1,80) = 0.06, p = 0.80). There were no significant differences in the frequency of adverse effects (AEs) reported by those assigned to ketamine treatment groups (p > 0.21 for all AEs reported more than once), although women reported more headaches (12% vs. 6%, p = 0.30) and nausea (10% vs. 6%, p = 0.47). In comparing pre-vs. postmenopausal women, no differences in efficacy were observed (F(1,76) = 0.36, p = 0.55). Conclusions: Results do not support differential efficacy or tolerability of ketamine for the treatment of TRD between women and men, nor based on menopause status among women. However, larger trials with these a priori aims are needed to confirm these results.

Original languageEnglish (US)
Pages (from-to)166-171
Number of pages6
JournalJournal of Psychiatric Research
StatePublished - Mar 2019


  • Depression
  • Ketamine
  • Menopause
  • Sex differences
  • Treatment resistant

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry


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