Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial
By J. Murrough, D. Iosifescu, Lee C Chang, Rayan K. Al Jurdi, C. Green, A. M. Perez, S. Iqbal, S. Pillemer, A. Foulkes, Asim A. Shah and 2 more. American Journal of Psychiatry, 2013
1,140 citations recorded by the source corpus.
Objective Ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, has shown rapid antidepressant effects, but small study groups and inadequate control conditions in prior studies have precluded a definitive conclusion. The authors evaluated the rapid antidepressant efficacy of ketamine in a large group of patients with treatment-resistant major depression. Method This was a two-site, parallel-arm, randomized controlled trial of a single infusion of ketamine compared to an active placebo control condition, the anesthetic midazolam. Patients with treatment-resistant major depression experiencing a major depressive episode were randomly assigned under double-blind conditions to receive a single intravenous infusion of ketamine or midazolam in a 2:1 ratio (N=73). The primary outcome was change in depression severity 24 hours after drug administration, as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS). Results The ketamine group had greater improvement in the MADRS score than the midazolam group 24 hours after treatment. After adjustment for baseline scores and site, the MADRS score was lower in the ketamine group than in the midazolam group by 7.95 points (95% confidence interval [CI], 3.20 to 12.71). The likelihood of response at 24 hours was greater with ketamine than with midazolam (odds ratio, 2.18; 95% CI, 1.21 to 4.14), with response rates of 64% and 28%, respectively. Conclusions Ketamine demonstrated rapid antidepressant effects in an optimized study design, further supporting NMDA receptor modulation as a novel mechanism for accelerated improvement in severe and chronic forms of depression. More information on response durability and safety is required before implementation in clinical practice.
Subfields: Biological Psychiatry, Cellular and Molecular Neuroscience, Pharmacology
View Paper: https://www.semanticscholar.org/paper/e34f931c9acf4eb7089a7a613a81eed1d3cfa069
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Biological Psychiatry
In Cellular and Molecular Neuroscience
In Pharmacology
Citations in the corpus
- The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis (2017, neutral): “(14) 73 35 Inpatient/ outpatient Midazolam Major depression 0 0”
- The Link between Depression and Chronic Pain: Neural Mechanisms in the Brain (2017, background): “However, such drugs have side effects such as dizziness, blurred vision, headache, nausea or vomiting, dry mouth, poor coordination, and restlessness [110].”
- Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders (2015, background): “Studies investigating its therapeutic effects have found a reduction in depressive symptoms in those suffering from treatment resistant depression along with mitigation of suicidality (Murrough et al., 2013; Price et al., 2009).”
- Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial (2018, background): “While we find a response rate to placebo of 46% at D1, and 26% at D7, ketamine trials have found a placebo effect of the order of 0 – 6% at D1, and 0 – 11% at D7 (Berman et al. , 2000; Zarate et al. , 2006; Murrough et al. , 2013; Lapidus et al. , 2014).”
- Dopamine System Dysregulation in Major Depressive Disorders (2017, background): “In depressed patients, ketamine, a non-competitive, glutamatergic N-methyl-d-aspartate receptor antagonist, exerts rapid (within hours) and prolonged (up to 1–2 weeks) antidepressant effects after a single dose (Berman et al., 2000; Zarate et al., 2006; Murrough et al., 2013).”