Regarding the two studies only assessing effects on MDD, Zarate and colleagues undertook a cross-over RCT on 17 participants off psychotropics for 2 weeks who received either ketamine or placebo saline infusion 1 week apart [Zarate et al. 2006]. Ketamine demonstrated a significant improvement over placebo at 24 hours (effect size

for drug difference d = 1.46; 95% confidence interval [CI] 0.91–2.01) and at 1 week (d = 0.68; 95% CI 0.13–1.23). Inhibitors,research,lifescience,medical A total of 71% of those administered ketamine met response criteria and 29% met remission criteria, measured on the HAMD, at 24 hours. Valentine and colleagues had a similar design, although in a smaller cohort (n = 10) and with a MLN0128 primary aim of evaluating changes in occipital Inhibitors,research,lifescience,medical amino acid neurotransmitters (discussed earlier in this paper) [Valentine et al. 2010]. They similarly found rapid antidepressant effects in the active group that were statistically significantly greater than that of the placebo group (HDRS score main effect of treatment (F(1,131) = 11.84, p < 0.0008). An earlier, but methodologically similar, study by Berman and colleagues included individuals with bipolar depression, although Inhibitors,research,lifescience,medical of the nine participants, only one had a bipolar depression, with the rest having a history of MDD [Berman et al.

2000]. At the time point 230 minutes post-ketamine infusion HAMD and HDRS scores displayed statistically significant improvements over placebo and 72 Inhibitors,research,lifescience,medical hours post-ketamine infusion

HAMD scores were reduced by an average of 48%. The two studies investigating the effect of ketamine in bipolar depression yielded similar positive results [DiazGranados et al. 2010b; Zarate et al. 2012]. Within 40 minutes of ketamine infusion, depressive symptoms significantly improved compared with placebo administration, remaining significant to day 3 in both studies (p < 0.001). DiazGranados and colleagues found an effect size of d = 0.52 (95% CI 0.28–0.76) at 40 minutes, d = 0.67 (95% CI 0.42–0.91) at 1 day and d = 0.22 (95% CI −0.03 to 0.48) at day 14 [DiazGranados et Inhibitors,research,lifescience,medical al. 2010b]. The largest effect size recorded by DiazGranados and colleagues was at 2 days post-infusion, d = 0.80 (95% CI 0.55–1.04). The work by Zarate and colleagues was with 14 subjects with treatment-resistant bipolar depression already stabilized Thymidine kinase on either lithium or lamotrigine who received either ketamine or saline infusions on two test days a fortnight apart [Zarate et al. 2012]. The authors reported a moderate to large drug effect size of d = 0.89 (95% CI 0.61–1.16) at 40 minutes through to 230 minutes (d = 0.85; 95% CI 0.57–1.14), at day 1 (d = 0.70; 95% CI 0.42–0.98) and at day 2 (d = 0.65; 95% CI 0.37–0.93), whilst the placebo showed no significant change in symptomatology. The largest effect size recorded by Zarate and colleagues was at 40 minutes post-infusion. Response rates were comparable at between 71% and 79%, as were remission rates of between 29% and 31%.