TY - JOUR
T1 - Sex differences in response to ketamine as a rapidly acting intervention for treatment resistant depression
AU - Freeman, Marlene P.
AU - Papakostas, George I.
AU - Hoeppner, Bettina
AU - Mazzone, Erica
AU - Judge, Heidi
AU - Cusin, Cristina
AU - Mathew, Sanjay
AU - Sanacora, Gerard
AU - Iosifescu, Dan
AU - DeBattista, Charles
AU - Trivedi, Madhukar H.
AU - Fava, Maurizio
N1 - Funding Information:
National Institute of Mental Health; NIH-NIMH HHSN271201100006I.
Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2019/3
Y1 - 2019/3
N2 - 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.
AB - 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.
KW - Depression
KW - Ketamine
KW - Menopause
KW - Sex differences
KW - Treatment resistant
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U2 - 10.1016/j.jpsychires.2019.01.010
DO - 10.1016/j.jpsychires.2019.01.010
M3 - Article
C2 - 30641350
AN - SCOPUS:85060346474
SN - 0022-3956
VL - 110
SP - 166
EP - 171
JO - Journal of Psychiatric Research
JF - Journal of Psychiatric Research
ER -