OBJECTIVE:Ketamine, 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. METHOD: In 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). RESULTS:In 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. CONCLUSIONS: Twice-weekly and thrice-weekly administration of ketamine at 0.5 mg/kg similarly maintained antidepressant efficacy over 15 days.
RCT Entities:
OBJECTIVE:Ketamine, 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. METHOD: In 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). RESULTS: In 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. CONCLUSIONS: Twice-weekly and thrice-weekly administration of ketamine at 0.5 mg/kg similarly maintained antidepressant efficacy over 15 days.
Authors: P Molero; J A Ramos-Quiroga; R Martin-Santos; E Calvo-Sánchez; L Gutiérrez-Rojas; J J Meana Journal: CNS Drugs Date: 2018-05 Impact factor: 5.749
Authors: Jason Ng; Leanna M W Lui; Joshua D Rosenblat; Kayla M Teopiz; Orly Lipsitz; Danielle S Cha; Jiaqi Xiong; Flora Nasri; Yena Lee; Kevin Kratiuk; Nelson B Rodrigues; Hartej Gill; Mehala Subramaniapillai; Rodrigo B Mansur; Roger Ho; Bing Cao; Roger S McIntyre Journal: Psychopharmacology (Berl) Date: 2021-01-23 Impact factor: 4.530
Authors: Samuel T Wilkinson; Rachel B Katz; Mesut Toprak; Ryan Webler; Robert B Ostroff; Gerard Sanacora Journal: J Clin Psychiatry Date: 2018-07-24 Impact factor: 4.384
Authors: Panos Zanos; Ruin Moaddel; Patrick J Morris; Lace M Riggs; Jaclyn N Highland; Polymnia Georgiou; Edna F R Pereira; Edson X Albuquerque; Craig J Thomas; Carlos A Zarate; Todd D Gould Journal: Pharmacol Rev Date: 2018-07 Impact factor: 25.468
Authors: Jennifer B Dwyer; Argyris Stringaris; David A Brent; Michael H Bloch Journal: J Child Psychol Psychiatry Date: 2020-02-04 Impact factor: 8.982
Authors: G Sanacora; H Heimer; D Hartman; S J Mathew; M Frye; C Nemeroff; R Robinson Beale Journal: Neuropsychopharmacology Date: 2016-09-19 Impact factor: 7.853