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

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.

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.

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 (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.

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.