Table 2.
Effectiveness Outcomes.*
| Outcome | Step 1 | Step 2 | |||
|---|---|---|---|---|---|
| Aripiprazole-Augmentation Group (N = 211) | Bupropion-Augmentation Group (N = 206) | Switch-to-Bupropion Group (N = 202) | Lithium-Augmentation Group (N = 127) | Switch-to-Nortriptyline Group (N = 121) | |
| Primary outcome | |||||
| Psychological well-being† | |||||
| Baseline | |||||
| No. of patients evaluated | 183 | 180 | 176 | 113 | 108 |
| Least-squares mean T score (95% CI) | 33.32 (32.23 to 34.42) | 33.68 (32.58 to 34.78) | 33.22 (32.11 to 34.32) | 31.62 (30.16 to 33.09) | 32.42 (30.92 to 33.92) |
| Wk 10 | |||||
| No. of patients evaluated | 170 | 159 | 140 | 96 | 95 |
| Least-squares mean T score (95% CI) | 38.16 (37.02 to 39.29) | 38.02 (36.87 to 39.16) | 35.26 (34.04 to 36.48) | 34.79 (33.21 to 36.38) | 34.60 (33.00 to 36.19) |
| Change from baseline (95% CI) ‡ | 4.83 (3.28 to 6.38) | 4.33 (2.76 to 5.91) | 2.04 (0.43 to 3.66) | 3.17 (1.12 to 5.22) | 2.18 (0.10 to 4.26) |
| Secondary outcomes § | |||||
| Remission¶ | |||||
| No. (%) | 61 (28.9) | 58 (28.2) | 39 (19.3) | 24 (18.9) | 26 (21.5) |
| Risk ratio vs. switch group (95% CI) | 1.50 (1.06 to 2.13) | 1.49 (1.04 to 2.12) | 1.00 (reference) | 0.84 (0.53 to 1.36) | 1.00 (reference) |
| MADRS score | |||||
| Baseline | |||||
| No. of patients evaluated | 203 | 199 | 194 | 126 | 120 |
| Least-squares mean score (95% CI) | 23.55 (22.44 to 24.67) | 22.97 (21.85 to 24.10) | 22.67 (21.53 to 23.81) | 23.61 (22.08 to 25.15) | 24.45 (22.87 to 26.03) |
| Wk 10 | |||||
| No. of patients evaluated | 183 | 175 | 163 | 116 | 108 |
| Least-squares mean score (95% CI) | 15.96 (14.79 to 17.12) | 15.74 (14.55 to 16.94) | 18.53 (17.29 to 19.76) | 18.98 (17.32 to 20.64) | 19.12 (17.44 to 20.80) |
| Change from baseline (95% CI)‖ | −7.60 (−9.20 to−5.99) | −7.23 (−8.86 to −5.59) | −4.14 (−5.81 to −2.48) | −4.63 (−6.78 to −2.49) | −5.33 (−7.52 to−3.14) |
| Social participation** | |||||
| Baseline | |||||
| No. of patients evaluated | 179 | 176 | 174 | 113 | 107 |
| Least-squares mean T score (95% CI) | 41.20 (40.09 to 42.31) | 42.09 (40.97 to 43.22) | 41.17 (40.03 to 42.32) | 42.43 (41.02 to 43.85) | 42.10 (40.65 to 43.56) |
| Wk 10 | |||||
| No. of patients evaluated | 168 | 159 | 140 | 96 | 94 |
| Least-squares mean T score (95% CI) | 44.29 (43.14 to 45.44) | 44.55 (43.40 to 45.70) | 43.12 (41.88 to 44.36) | 43.89 (42.36 to 45.43) | 43.67 (42.12 to 45.22) |
| Change from baseline (95% CI)†† | 3.09 (1.51 to 4.68) | 2.46 (0.86 to 4.06) | 1.95 (0.29 to 3.60) | 1.46 (−0.53 to 3.44) | 1.57 (−0.45 to 3.58) |
| Physical function** | |||||
| Baseline | |||||
| No. of patients evaluated | 183 | 180 | 177 | 113 | 108 |
| Least-squares mean T score (95% CI) | 42.14 (41.01 to 43.27) | 40.93 (39.82 to 42.05) | 41.44 (40.29 to 42.59) | 41.30 (39.83 to 42.76) | 41.46 (39.94 to 42.97) |
| Wk 10 | |||||
| No. of patients evaluated | 170 | 159 | 140 | 97 | 95 |
| Least-squares mean T score (95% CI) | 42.10 (40.95 to 43.25) | 41.46 (40.25 to 42.67) | 41.11 (39.83 to 42.39) | 42.79 (41.21 to 44.37) | 42.45 (40.84 to 44.06) |
| Change from baseline (95% CI)‡‡ | −0.03 (−1.64 to 1.57) | 0.53 (−1.10 to 2.15) | −0.33 (−2.06 to 1.40) | 1.50 (−0.56 to 3.56) | 1.00 (−1.09 to 3.09) |
Shown are best estimates of change (least-squares mean and 95% confidence interval) for each trial group. Observed mean change scores are provided in Table S4.
Scores were calculated as the average T scores of two fixed-length surveys from the National Institutes of Health Toolbox Emotion Battery subscales for Positive Affect and General Life Satisfaction. The normative population mean is 50, with higher scores indicating higher levels of psychological well-being.
In step 1, the difference between the aripiprazole-augmentation group and the switch-to-bupropion group was 2.79 (95% CI, 0.56 to 5.02; P = 0.014, with a threshold P value of 0.017; Cohen’s d, 0.37; 95% CI, 0.07 to 0.67). The difference between the bupropion-augmentation group and the switch-to-bupropion group was 2.29 (95% CI, 0.01 to 4.57; P = 0.05, with a threshold P value of 0.025). The difference between the aripiprazole-augmentation group and the bupropion-augmentation group was 0.50 (95% CI, −1.69 to 2.69; P = 0.66). In step 2, the difference between the lithium-augmentation group and the switch-to-nortriptyline group was 0.99 (95% CI, −1.92 to 3.91).
For secondary outcomes, the widths of the confidence intervals for between-group differences were not adjusted for multiple comparisons, and no definite conclusions can be drawn from these data.
Remission was defined as a reduction in depressive symptoms over a period of 10 weeks with a final Montgomery–Asberg Depression Rating Scale (MADRS) score of 10 or less (range, 0 to 60, with higher scores indicating greater severity of depressive symptoms). If no MADRS score was available but a PHQ-9 score was available, a PHQ-9 score of 5 or less was considered to indicate remission.
In step 1, the between-group differences were as follows: aripiprazole-augmentation group and switch-to-bupropion group, −3.45 (95% CI, −5.76 to −1.14); bupropion-augmentation group and switch-to-bupropion group, −3.08 (95% CI, −5.42 to −0.75); and aripiprazole-augmentation group and bupropion-augmentation group, −0.37 (95% CI, −2.66 to 1.93). In step 2, the between-group difference was 0.70 (95% CI, −2.37 to 3.76).
Scores are based on the Patient-Reported Outcomes Measurement Information System (PROMIS) scales for social participation and physical function. Mean (±SD) T scores are 50±10, with higher scores indicating higher levels of social participation or physical function.
In step 1, the between-group differences were as follows: aripiprazole-augmentation group and switch-to-bupropion group, 1.15 (95% CI, −1.14 to 3.44); bupropion-augmentation group and switch-to-bupropion group, 0.51 (95% CI, −1.74 to 2.77); and aripiprazole-augmentation group and bupropion-augmentation group, 0.63 (95% CI, −1.61 to 2.88). In step 2, the between-group difference was −0.11 (95% CI, −2.94 to 2.72).
In step 1, the between-group differences were as follows: aripiprazole-augmentation group and switch-to-bupropion group, 0.30 (95% CI, −2.03 to 2.62); bupropion-augmentation group and switch-to-bupropion group, 0.86 (95% CI, −1.49 to 3.21); and aripiprazole-augmentation group and bupropion-augmentation group, −0.56 (95% CI, −2.83 to 1.70). In step 2, the between-group difference was 0.50 (95% CI, −2.42 to 3.42).