A transdiagnostic systematic review and meta-analysis of ketamine's anxiolytic effects
This transdiagnostic meta-analysis of 14 randomised controlled trials (most with high risk of bias) found that ketamine produced significant anxiolytic effects versus placebo at acute (<12 h; SMD −1.17), subacute (24 h; SMD −0.44) and sustained (7–14 days; SMD −0.40) time points. Subacute and sustained anxiety improvements correlated with antidepressant effects but not with peak dissociation, suggesting ketamine provides rapid and 1–2 week anxiety relief across clinical settings.
Authors
- Allan Young
- Luke Jelen
Published
Abstract
Background
Ketamine may be effective in treating symptoms of anxiety, but the time profile of ketamine’s anxiolytic effect is ill-defined. This systematic review and meta-analysis investigated the anxiolytic effect of ketamine at different time points across a range of clinical settings.
Methods
Electronic databases were searched to capture randomised control trials measuring the anxiolytic effects of ketamine in contexts including mood disorders, anxiety disorders and chronic pain. Meta-analyses were conducted using a random-effects model. The correlations between (1) improvements in mean anxiety and depression scores, and (2) peak dissociation and improvements in mean anxiety scores were also assessed.
Results
In all, 14 studies met inclusion criteria. Risk of bias was high in 11 studies. Ketamine significantly reduced anxiety scores compared to placebo at acute (<12 h; standard mean difference (SMD): −1.17, 95% confidence interval (CI) [−1.89, −0.44], p < 0.01), subacute (24 h; SMD: −0.44, 95% CI [−0.65, −0.22], p < 0.01) and sustained (7–14 days; SMD: −0.40, 95% CI [−0.63, −0.17], p < 0.01) time points. Exploratory analyses revealed improvements in anxiety and depression symptoms correlated at both subacute ( R 2 = 0.621, p = 0.035) and sustained time points ( R 2 = 0.773, p = 0.021). The relationship between peak dissociation and improvement in anxiety was not significant.
Conclusions
Ketamine appears to offer rapid and sustained anxiety symptom relief across a range of clinical settings, with anxiolytic effects occurring within the first 12 h of administration and remaining effective for 1–2 weeks. Future studies could explore the effects of ketamine maintenance therapy on anxiety symptoms.
Research Summary of 'A transdiagnostic systematic review and meta-analysis of ketamine's anxiolytic effects'
Introduction
Anxiety disorders are highly prevalent and cause substantial impairment; significant anxiety symptoms also occur across other clinical settings such as major depressive disorder, chronic pain, advanced cancer and palliative care. Existing pharmacotherapies have limitations: selective serotonin reuptake inhibitors (SSRIs) act slowly and can initially worsen anxiety, while benzodiazepines act rapidly but carry risks of tolerance and dependence. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has established rapid antidepressant effects and growing evidence suggests it may also reduce anxiety symptoms across diagnostic categories, but the time course of any anxiolytic effect is uncertain and previous reviews have included lower-quality designs and non-blinded studies. Hartland and colleagues set out to quantify ketamine's anxiolytic effects using a transdiagnostic approach limited to blinded, randomised, placebo-controlled trials. The principal aim was to synthesise RCT evidence at prespecified time windows — acute (<12 hours), subacute (24 hours) and sustained (7–14 days) after a single ketamine dose — and to explore correlations between anxiety improvements and both depressive symptom change and peak dissociative effects.
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Study Details
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- APA Citation
Hartland, H., Mahdavi, K., Jelen, L. A., Strawbridge, R., Young, A. H., & Alexander, L. (2023). A transdiagnostic systematic review and meta-analysis of ketamine's anxiolytic effects. Journal of Psychopharmacology, 37(8), 764-774. https://doi.org/10.1177/02698811231161627
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