• Jaskaran B Singh, Maggie Fedgchin, Ella J Daly, Peter De Boer, Kimberly Cooper, Pilar Lim, Christine Pinter, James W Murrough, Gerard Sanacora, Richard C Shelton, Benji Kurian, Andrew Winokur, Maurizio Fava, Husseini Manji, Wayne C Drevets, and Luc Van Nueten.
• From Janssen Research and Development, Titusville, N.J., and Beerse, Belgium; the Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, N.Y.; the Department of Psychiatry, Yale University, New Haven, Conn.; the Department of Psychiatry and Behavioral Neurobiology, School of Medicine, University of Alabama at Birmingham; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; the Institute of Living, Hartford, Conn.; University of Connecticut Health Center, Farmington; the Department of Psychiatry, Massachusetts General Hospital, Boston.
• Am J Psychiatry. 2016 Aug 1; 173 (8): 816-26.

ObjectiveKetamine, an N-methyl-d-aspartate glutamate receptor antagonist, has demonstrated a rapid-onset antidepressant effect in patients with treatment-resistant depression. This study evaluated the efficacy of twice- and thrice-weekly intravenous administration of ketamine in sustaining initial antidepressant effects in patients with treatment-resistant depression.MethodIn a multicenter, double-blind study, adults (ages 18-64 years) with treatment-resistant depression were randomized to receive either intravenous ketamine (0.5 mg/kg of body weight) or intravenous placebo, administered over 40 minutes, either two or three times weekly, for up to 4 weeks. Patients who discontinued double-blind treatment after at least 2 weeks for lack of efficacy could enter an optional 2-week open-label phase to receive ketamine with the same frequency as in the double-blind phase. The primary outcome measure was change from baseline to day 15 in total score on the Montgomery-Åsberg Depression Rating Scale (MADRS).ResultsIn total, 67 (45 women) of 68 randomized patients received treatment. In the twice-weekly dosing groups, the mean change in MADRS score at day 15 was -18.4 (SD=12.0) for ketamine and -5.7 (SD=10.2) for placebo; in the thrice-weekly groups, it was -17.7 (SD=7.3) for ketamine and -3.1 (SD=5.7) for placebo. Similar observations were noted for ketamine during the open-label phase (twice-weekly, -12.2 [SD=12.8] on day 4; thrice-weekly, -14.0 [SD=12.5] on day 5). Both regimens were generally well tolerated. Headache, anxiety, dissociation, nausea, and dizziness were the most common (≥20%) treatment-emergent adverse events. Dissociative symptoms occurred transiently and attenuated with repeated dosing.ConclusionsTwice-weekly and thrice-weekly administration of ketamine at 0.5 mg/kg similarly maintained antidepressant efficacy over 15 days.

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