A Double-Blind, Randomized, Placebo-Controlled, Dose-Frequency Study of Intravenous Ketamine in Patients With Treatment-Resistant Depression
Jaskaran Singh, Maggie Fedgchin, Ella Daly, Peter de Boer, Kimberly Cooper, Pilar Lim, Christine Pinter, James W. Murrough, Gerard Sanacora, Richard C. Shelton, Benji T. Kurian, Andrew Winokur, Maurizio Fava, Husseini Manji, Wayne C. Drevets, Luc Van Nueten
American Journal of Psychiatry April 8, 2016 DOI: 10.1176/appi.ajp.2016.16010037 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Open-label Peer reviewed |
|---|---|
| Sample size | 67 |
| Population | Adults (ages 18-64) with treatment-resistant depression |
| Intervention | Intravenous ketamine |
| Dose | 0.5 mg/kg |
| Duration | Up to 4 weeks, with primary outcome at day 15 |
| Topics | Depression Ketamine Esketamine |
| Keywords | Placebo Anesthesia Dosing Randomized controlled trial Depression economics Antidepressant |
| Citations | 530 |
| Key findings | Twice-weekly and thrice-weekly intravenous ketamine at 0.5 mg/kg similarly maintained antidepressant efficacy over 15 days, with both regimens producing substantially greater reductions in depression scores than placebo. |
Abstract
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.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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Twice-weekly and thrice-weekly intravenous ketamine at 0.5 mg/kg similarly maintained antidepressant efficacy over 15 days, with substantially greater MADRS reductions than placebo.
Synthesized
Comparable studies
Other randomized controlled trials on ketamine for depression, most cited first.