Table 1. MADRS Total Score: Change From Baseline to 2 Hours, 24 Hours, and Period End Point.
| Variablea | Placebo | Esketamine 28 mg | Esketamine 56 mg | Esketamine 84 mg |
|---|---|---|---|---|
| Period 1 | ||||
| No. | 33 | 11 | 11 | 12 |
| MADRS total score at baseline, mean (SD) | 35.0 (5.18) | 31.3 (3.80) | 33.2 (6.26) | 35.0 (4.22) |
| Change at 2 h | ||||
| LS mean change (SE) | −9.7 (1.76) | −16.4 (2.76) | −14.3 (2.70) | −17.6 (2.60) |
| LS mean difference from placebo (SE) | −6.7 (3.03) | −4.6 (2.96) | −7.9 (2.84) | |
| P value | .02 | .06 | .003 | |
| Responders, No. (%) | 6 (18) | 6 (55) | 4 (36) | 7 (58) |
| Remitters, No. (%) | 1 (3) | 3 (27) | 2 (18) | 3 (25) |
| Change at 24 h | ||||
| LS mean change (SE) | −5.7 (1.79) | −14.8 (2.80) | −15.7 (2.74) | −16.4 (2.64) |
| LS mean difference from placebo (SE) | −9.1 (3.08) | −10.0 (3.00) | −10.7 (2.88) | |
| P value | .002 | <.001 | <.001 | |
| Responders, No. (%) | 1 (3) | 4 (36) | 3 (27.3) | 5 (42) |
| Remitters, No. (%) | 0 | 4 (36) | 2 (18) | 3 (25) |
| Change at study period end point | ||||
| LS mean change (SE) | −4.9 (1.74) | −9.8 (2.72) | −12.4 (2.66) | −15.3 (2.56) |
| LS mean difference from placebo (SE) | −5.0 (2.99) | −7.6 (2.91) | −10.5 (2.79) | |
| P value | .05 | .006 | <.001 | |
| Responders, No. (%) | 2 (6) | 1 (9) | 2 (18) | 5 (42) |
| Remitters, No. (%) | 1 (3) | 1 (9) | 1 (9) | 3 (25) |
| Period 2b | ||||
| No. | 6 | 8 | 9 | 5 |
| MADRS total score at baseline, mean (SD) | 29.3 (5.79) | 31.3 (7.09) | 34.9 (6.13) | 30.4 (4.67) |
| Change at 2 h | ||||
| LS mean change (SE) | −6.8 (3.74) | −10.3 (3.18) | −11.7 (3.22) | −11.6 (3.44) |
| LS mean difference from placebo (SE) | −3.5 (3.82) | −4 (3.92) | −4.9 (4.36) | |
| P value | .18 | .11 | .14 | |
| Responders, No. (%) | 1 (17) | 1 (13) | 2 (22) | 2 (40) |
| Remitters, No. (%) | 1 (17) | 1 (13) | 0 | 2 (40) |
| Change at 24 h | ||||
| LS mean change (SE) | −4.1 (4.09) | −8.9 (3.48) | −10.2 (3.52) | −11.6 (3.76) |
| LS mean difference from placebo (SE) | −4.8 (4.18) | −6.1 (4.29) | −7.5 (4.77) | |
| P value | .13 | .09 | .07 | |
| Responders, No. (%) | 0 | 0 | 1 (11) | 2 (40) |
| Remitters, No. (%) | 0 | 0 | 0 | 1 (20) |
| Change at study period end point | ||||
| LS mean change (SE) | −4.5 (2.92) | −7.6 (2.49) | −8.9 (2.51) | −11.4 (2.68) |
| LS mean difference from placebo (SE) | −3.1 (2.99) | −4.4 (3.06) | −6.9 (3.41) | |
| P value | .15 | .08 | .03 | |
| Responders, No. (%) | 0 | 1 (13) | 0 | 1 (20) |
| Remitters, No. (%) | 0 | 1 (13) | 0 | 1 (20) |
| Periods 1 and 2 Combined | ||||
| Mean difference from placebo (SE) | −4.2 (2.09) | −6.3 (2.07) | −9.0 (2.13) | |
| 90% CI for mean difference vs placebo | −7.67 to −0.79 | −9.71 to −2.88 | −12.53 to −5.52 | |
| Combined period test statistic | −2.02 | −3.04 | 4.24 | |
| P value | .02 | .001 | <.001 | |
Abbreviations: LS, least squares; MADRS, Montgomery-Åsberg Depression Rating Scale.
a
Period 1 (days 1-8) and period 2 (days 8-15) are discussed in the Design section of the Methods and shown in the vertical axis of Figure 1.
b
The study samples reported for period 2 include only the placebo nonresponsive participants rerandomized following period 1.