American Journal of Psychiatry
October 3, 2017
S. Wilkinson, Elizabeth D. Ballard, M. Bloch et al.
680 citations
A single dose of ketamine rapidly reduces suicidal thoughts within one day and for up to one week in depressed patients with suicidal ideation. The effect is moderate to large and partially independent of changes in depressive symptoms. The analysis combined data from 167 participants across 10 studies comparing ketamine to a placebo (saline or midazolam). Ketamine significantly improved clinician-rated and self-reported suicidal ideation, though not on one self-report measure (the Beck Depression Inventory). The authors call for further research on long-term safety and suicide risk reduction before clinical use.
Molecular Psychiatry
October 3, 2018
M. Fava, M. Freeman, M. Flynn et al.
438 citations
Intravenous ketamine at 0.5 mg/kg and 1.0 mg/kg produces rapid antidepressant effects in adults with treatment-resistant depression, with most improvement seen one day after a single 40-minute infusion. Lower doses (0.1 mg/kg and 0.2 mg/kg) did not show consistent benefit. The study compared four ketamine doses against an active placebo (midazolam) in 99 outpatients across six U.S. sites. Higher doses caused more dissociative symptoms and temporary blood pressure increases, but infusions were generally well tolerated. The findings indicate a range of effective subanesthetic doses, with no clear advantage for doses below 0.5 mg/kg.
New England Journal of Medicine
May 24, 2023
A. Anand, S. Mathew, G. Sanacora et al.
263 citations
For treatment-resistant major depression without psychosis, intravenous ketamine is at least as effective as electroconvulsive therapy (ECT). In a randomized trial with 403 patients, 55.4% of those receiving ketamine and 41.2% of those receiving ECT showed a 50% or greater reduction in depression scores over three weeks. ECT was linked to a notable decline in memory recall after three weeks (average decrease of 9.7 points on a memory test vs. 0.9 points with ketamine), with gradual recovery during follow-up. Quality-of-life improvements were similar between groups. Ketamine caused dissociation, while ECT led to musculoskeletal side effects.
JAMA psychiatry
October 19, 2022
T. Rhee, S. Shim, B. Forester et al.
139 citations
A systematic review and meta-analysis of six clinical trials involving 340 patients with major depressive episodes found that electroconvulsive therapy (ECT) was more effective than ketamine for reducing depression severity in the acute phase, with a standardized mean difference of -0.69 favoring ECT. No significant differences were observed between the two treatments for cognition, memory, or serious adverse events. Ketamine carried lower risks of headache and muscle pain, while ECT carried lower risks of blurred vision, vertigo, diplopia, and dissociative symptoms. The findings suggest ECT may be superior, but treatment decisions should be individualized.
Contemporary Clinical Trials
February 1, 2019
S. Mathew, S. Wilkinson, Murat Altinay et al.
54 citations
Electroconvulsive therapy (ECT) and ketamine show similar response rates for treatment-resistant depression, but a head-to-head comparison in a large, well-powered trial has been lacking. This protocol describes a non-inferiority trial randomizing 400 patients with treatment-resistant depression to receive either ECT thrice weekly or intravenous ketamine twice weekly for 3-5 weeks. The primary outcome is the proportion of responders based on a patient-reported depression scale. The study is designed to determine whether ketamine retains at least 90% of ECT's treatment effect. Results will inform patient choice, clinical practice, and insurance policies.
Clinical psychological science : a journal of the Association for Psychological Science
June 20, 2017
Vaughan Bell, K. Mills, G. Modinos et al.
A debate about how to study psychosis in cognitive science is addressed. The authors agree with critics that the subjective experience of psychosis, especially the presence of illusory social agents, cannot be reduced to simple cognitive errors. They argue that current social-cognition models neglect this central phenomenological feature. They propose that research should also examine how social agents are represented and deployed, not just how social information is processed. They suggest that intersubjective instability in psychosis may be reorganized into illusory social agents as a best-fit explanation, a hypothesis for future study. They advocate for a phenomenologically informed cognitive science to better understand psychosis.