Primary and secondary efficacy measures: change from baseline to week 8, intent-to-treat population
| Outcomes | Placebo, n = 185 | Levomilnacipran ER, 40 mg/day, n = 185 | Levomilnacipran ER, 80 mg/day, n = 187 |
|---|---|---|---|
| Primary efficacy parameter; MADRS total score | |||
| Baseline, mean ± SD | 31.0 ± 3.8 | 30.8 ± 3.4 | 31.2 ± 3.5 |
| MMRM | |||
| Change at week 8, LSM (SE) | −11.3 (0.77) | −14.6 (0.79) | −14.4 (0.79) |
| LSMD v. placebo (95% CI) | — | −3.3 (−5.5 to −1.1) | −3.1 (−5.3 to −1.0) |
| p value | — | 0.003 | 0.004 |
| LOCF | |||
| Change at week 8, LSM (SE) | −10.7 (0.77) | −13.1 (0.79) | −13.1 (0.76) |
| LSMD v. placebo (95% CI) | — | −2.4 (−4.5 to −0.3) | −2.4 (−4.5 to −0.3) |
| p value | — | 0.025 | 0.024 |
| Secondary efficacy parameter; SDS total score* | |||
| Baseline, mean ± SD | 16.4 ± 6.1 | 16.7 ± 6.6 | 17.6 ± 6.0 |
| MMRM | |||
| Change at week 8, LSM (SE) | −5.4 (0.66) | −7.3 (0.68) | −8.2 (0.66) |
| LSMD v. placebo (95% CI) | — | −1.8 (−3.6 to 0.0) | −2.7 (−4.5 to −0.9) |
| p value | — | 0.046 | 0.003 |
| LOCF | |||
| Change at week 8, LSM (SE) | −5.0 (0.7) | −6.7 (0.7) | −7.4 (0.6) |
| LSMD v. placebo (95% CI) | — | −1.7 (−3.4 to 0.1) | −2.5 (−4.2 to −0.7) |
| p value | — | 0.06 | 0.006 |
| SDS subscales; MMRM | |||
| Work | |||
| Baseline, mean ± SD | 5.1 ± 2.5 | 5.1 ± 2.7 | 5.4 ± 2.3 |
| Change at week 8, LSM (SE) | −1.4 (0.23) | −2.3 (0.24) | −2.5 (0.23) |
| LSMD v. placebo (95% CI) | — | −0.9 (−1.5 to −0.3) | −1.1 (−1.7 to −0.5) |
| p value | — | 0.005 | < 0.001 |
| Social life | |||
| Baseline, mean ± SD | 6.0 ± 2.3 | 6.2 ± 2.5 | 6.3 ± 2.4 |
| Change at week 8, LSM (SE) | −2.0 (0.21) | −2.5 (0.22) | −2.4 (0.21) |
| LSMD v. placebo (95% CI) | — | −0.6 (−1.2 to 0.0) | −0.4 (−1.0 to 0.1) |
| p value | — | 0.06 | 0.14 |
| Family life | |||
| Baseline, mean ± SD | 5.7 ± 2.2 | 5.8 ± 2.4 | 6.1 ± 2.3 |
| Change at week 8, LSM (SE) | −1.8 (0.21) | −2.4 (0.21) | −2.3 (0.21) |
| LSMD v. placebo (95% CI) | — | −0.6 (−1.1 to 0.0) | −0.5 (−1.1 to 0.1) |
| p value | — | 0.06 | 0.09 |
CI = confidence interval; ER = extended-release; LOCF = last observation carried forward; LSM = least squares mean; LSMD = least squares mean difference; MADRS = Montgomery–Åsberg Depression Rating Scale; MMRM = mixed-effects model for repeated-measures; SD = standard deviation; SDS = Sheehan Disability Scale; SE = standard error.
↵* Analysis of SDS total score is based only on patients with valid responses on all 3 SDS items (MMRM: placebo = 98, 40 mg/day = 93, 80 mg/day = 94; LOCF: placebo = 118, 40 mg/day = 117, 80 mg/day = 127).