Table 3.
The Results of Meta-Analysis of Randomized, Active-Controlled Trials
| Efficacy | ||||||
|---|---|---|---|---|---|---|
| Outcome | Number of Studies | Number of Patients | I2 | Effect Size | 95% Confidence Interval | P |
| Study-defined relapse rate of depressive symptoms | 3 | 424 | 55% | Risk ratio = 1.25 | 0.60 to 2.59 | .55 |
| Young Mania Rating Scale total scores | 5 | 507 | 63% | Weighted mean differences = -1.03 | -3.24 to -1.18 | .36 |
| Montgomery-Asberg Depression Scale total scores | 4 | 478 | 37% | Weighted mean differences = 1.27 | -0.59 to 3.12 | .18 |
| Clinical Global Impressions-Severity scores | 5 | 507 | 77% | Weighted mean differences = -0.15 | -0.68 to 0.38 | .57 |
| Number of episodes (any symptoms) | 4 | 378 | 85% | Standardized mean difference = -0.05 | -0.73 to 0.62 | .87 |
| Number of episodes (manic/ hypomanic/ mixed symptoms) | 3 | 345 | 91% | Standardized mean difference = -0.34 | -1.28 to 0.60 | .48 |
| Number of episodes (depressive symptoms) | 3 | 345 | 88% | Standardized mean difference = 0.28 | -0.51 to 1.07 | .49 |
| Safety | ||||||
| Discontinuation due to all-cause | 6 | 576 | 70% | Risk ratio = 0.99 | 0.66 to 1.48 | .97 |
| Discontinuation due to adverse events | 6 | 576 | 0% | Risk ratio = 1.59 | 0.67 to 3.77 | .30 |
| Discontinuation due to death | 2 | 387 | na | Risk ratio = 0.45 | 0.04 to 4.88 | .51 |
| Discontinuation due to withdrawal consent | 4 | 484 | 22% | Risk ratio = 1.31 | 0.53 to 3.24 | .56 |
| At least one adverse event | 3 | 360 | 0% | Risk ratio = 0.99 | 0.92 to 1.05 | .67 |
| Serious adverse event | 3 | 221 | 4% | Risk ratio = 0.71 | 0.30 to 1.70 | .44 |
| Potential prolactin-related adverse events*, a | 4 | 480 | 0% | Risk ratio = 2.66 | 1.12 to 6.33 | .03 |
| Suicide attempts | 2 | 169 | na | Risk ratio = 2.73 | 0.11 to 65.68 | .54 |
| Sedation/somnolence | 4 | 480 | 56% | Risk ratio = 0.90 | 0.28 to 2.90 | .86 |
| Insomnia | 2 | 387 | 0% | Risk ratio = 1.38 | 0.85 to 2.23 | .19 |
| Asthenia/depression | 3 | 435 | 62% | Risk ratio = 0.77 | 0.14 to 4.42 | .77 |
| Use of benzodiazepines | 4 | 480 | 0% | Risk ratio = 0.99 | 0.67 to 1.47 | .96 |
| Fatigue | 2 | 387 | 0% | Risk ratio = 0.38 | 0.14 to 1.01 | .05 |
| Use of anticholinergic drugs | 2 | 93 | 68% | Risk ratio = 1.56 | 0.16 to 15.29 | .70 |
| Extrapyramidal symptoms/tremor | 3 | 217 | 0% | Risk ratio = 1.54 | 0.90 to 2.66 | .12 |
| Akathisia | 2 | 172 | 0% | Risk ratio = 0.99 | 0.33 to 2.97 | .98 |
| Migraine/headache | 3 | 435 | 68% | Risk ratio = 0.33 | 0.05 to 2.04 | .23 |
| Dizziness | 2 | 172 | 0% | Risk ratio = 0.64 | 0.19 to 2.20 | .48 |
| Upper respiratory infection | 2 | 172 | 0% | Risk ratio = 1.82 | 0.44 to 7.53 | .41 |
| Increased appetite | 2 | 311 | 0% | Risk ratio = 0.59 | 0.27 to 1.31 | .19 |
| Weight gain (≥7% increased) | 3 | 426 | 0% | Risk ratio = 0.74 | 0.54 to 1.02 | .07 |
| Body mass index/body weight | 2 | 163 | 47% | Standardized mean difference = 0.36 | -0.12 to 0.84 | .15 |
Abbreviations: na, not applicable.
Adverse events considered to be potentially prolactin-related (such as galactorrhea, menstrual changes or libido decreased), as reported by the investigator.
*Number need to harm = 20, P = .01.