A transdiagnostic systematic review and meta-analysis of ketamine's anxiolytic effects

Background: Subanaesthetic doses of ketamine may be effective in treating symptoms of anxiety, but the time profile of ketamines anxiolytic effect is ill-defined. This systematic review and meta-analysis of randomised controlled trials investigated the anxiolytic effect of ketamine at different time points across a range of clinical contexts. Methods: Electronic databases were searched to capture randomised control trials measuring the anxiolytic effects of ketamine across a range of clinical settings 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: 14 studies met inclusion criteria. Risk of bias was high in 11 studies. Ketamine significantly reduced anxiety scores compared to placebo at the acute (<12 hours; SMD: -1.07 [95% CI: -1.68, -0.46], p < 0.001), subacute (24 hours; SMD: -0.43 [95% CI: -0.65, -0.22], p < 0.001) and sustained (7-14 days; SMD: -0.43 [95% CI: -0.65, -0.20], p < 0.001) time points. Exploratory analyses revealed improvements in anxiety and depression symptoms correlated at both subacute (R2 = 0.621, p = 0.035) and sustained time points (R2 = 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 relief from anxiety symptoms across a range of clinical settings, with anxiolytic effects occurring within the first 12 hours of administration and remaining effective for one to two weeks. Future studies with improved blinding could explore ketamine maintenance therapy for anxiety.