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

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 (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 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.