Of the 79% who attained remission criteria at 24
hours in the work by Zarate and colleagues [Zarate et al. 2006], 35% were reported as maintaining this at 1 week, whilst Valentine and colleagues [Valentine et al. 2010] described the statistically significant improvement of the active treatment over the placebo group was sustained for a week. In the bipolar depression studies the mean time to relapse was reported as 4.5 days by Zarate and colleagues [Zarate et al. 2012], and Tyrosine Kinase Inhibitor Library although this figure was not documented by DiazGranados and colleagues [DiazGranados et al. 2010b], comparisons from baseline at days 7, 10 and 14 were no longer significant. Inhibitors,research,lifescience,medical The side effects recorded in the controlled studies were similar in nature and frequency to those of the open-label trials, with the active drug generally well tolerated, although distinctive transient dissociative Inhibitors,research,lifescience,medical and perceptual disturbances were noted in all trials, and likely to have affected study blinding. Meta-analysis of the double-blind RCTs of ketamine Meta-analysis of the double-blind RCTs supports the antidepressant efficacy
of ketamine. Figure 3 shows the difference between ketamine and placebo at baseline (top), 60–80 minutes (middle) and 210–230 minutes (bottom). At 60–80 minutes the mean difference in depression scores Inhibitors,research,lifescience,medical on the HDRS was −3.406 (p < 0.001; 95% CI −6.303 to −0.509) and at 210–230 minutes the mean difference was −5.371 (p < 0.001; 95% CI −6.574 to −4.168). Figure 3. Forest plots for the efficacy of ketamine compared with placebo at baseline Inhibitors,research,lifescience,medical (top), 60–80 minutes (middle)
and 210–230 minutes (bottom). Three studies [DiazGranados et al. 2010b; Valentine et al. 2011; Zarate et al. 2012] reported significant reductions in depression scores between 60 and 80 minutes, whilst the change was not statistically Inhibitors,research,lifescience,medical significant in two studies [Zarate et al. 2006; Berman et al. 2000]. Four studies report the change in depression scores at the 210–230 minute time point as statistically significant [Berman et al. 2000; DiazGranados et al. 2010b; Zarate et al. 2006, 2012], whilst one study [Valentine et al. 2011] reports the change in depression scores as not statistically significant. Berman and colleagues [Berman et al. 2000] reported a large disparity between baseline depression the scores in the placebo and ketamine condition, but this difference was deemed not statistically significant through a paired t test (p = 0.10). Thus, although the Forest plots reveal the mean difference between scores in the placebo and ketamine condition as relatively small, this is owing to the differences recorded at baseline. This disparity led to a heterogeneity p = 0.531 in the meta-analysis for 210–230 minutes, but the model showed a statistically significant effect of p < 0.001. The high heterogeneity evident at 60–80 minutes (I2 = 79%) is likely due to the figures reported by Berman and colleagues [Berman et al. 2000].