Quality of evidence was downgraded due to significant unexplained heterogeneity in some of the doses and outcomes. The results did not meet the clinically significant thresholds for NNT
| Reference | Study type | Population | Intervention and comparison | Outcomes | Risk of bias [Table «Additional comments for included studies...»2Additional comments] |
|---|---|---|---|---|---|
| SR=systematic review | |||||
| «Dutta S, Singhal S, Shah R, et al. Daridorexant as...»1 | SR | 4 RCT's with 2768 adult patients, including elderly | daridorexant 10mg, 25mg, or 50mg vs. placebo or zolpidem | 1. Wake After Sleep Onset (WASO) 2. Latency to Persistent Sleep (LPS) 3.Subjective Total Sleep Time (sTST) |
Low |
| «Chalet FX, Luyet PP, Rabasa C, et al. Daridorexant...»2 | RCT | 930 patients, post hoc-study | daridorexant 25 mg, 50mg or placebo | 1.NNT (number needed to treat) 2.NNH (number needed to harm) |
moderate |
| Reference | Comments |
|---|---|
| «Dutta S, Singhal S, Shah R, et al. Daridorexant as...»1 | Studies were well-designed, randomized, and double-blinded. One study had incomplete reporting of outcomes. GRADE and Cochrane tools were used for quality assessment. |
| «Chalet FX, Luyet PP, Rabasa C, et al. Daridorexant...»2 | The study recruited participants with a latency to persistent sleep (LPS) ≥20minutes, wakefulness after sleep onset (WASO) ≥30minutes, and mean total sleep time (TST) of <7hours, as measured by polysomnography recording during two consecutive nights. Overall, 930 patients were included (all randomized participants; 310 received daridorexant 25mg, 310 received daridorexant 50mg, and 310 received placebo). Mean age was 55.4years and 364 (39%) of the participants were ≥65years old. The majority of patients were female (67% among the treatment arms). |
Results
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Mean (SD) I | Mean (SD) C | Mean difference (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: moderate The quality of evidence is downgraded due to imprecision I= intervention; C=comparison; CI=confidence interval |
|||||
| «Dutta S, Singhal S, Shah R, et al. Daridorexant as...»1 | 25 mg 3 RCT (679/678) |
1 month | -38.9 (4.2) to -18.4 (33.3) | -33.8 (4.2) to -6.2 (33.4) | - 9.1 (-14.56,-3.65) |
| 25 mg 2 RCT (619/618) |
3 months | -24.25 (42.6) to -22.97 (35.7) | -14 (42.4) to -11.1 (36) | -11.19 (-15.51,-6.88) | |
| 50mg 2 RCT (371/370) |
1 month | -48 (4.1) to -28.98 (33) | -33.8 (4.2) to -6.2 (33.4) | -18.11 (-26.48,-9.73) | |
| «Chalet FX, Luyet PP, Rabasa C, et al. Daridorexant...»2 | |||||
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Mean (SD) I | Mean (SD) C | Mean Difference (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: moderate The quality of evidence is downgraded due to imprecision in 50mg dose (I2=60%) I= intervention; C=comparison; CI=confidence interval |
|||||
| «Dutta S, Singhal S, Shah R, et al. Daridorexant as...»1 | 25mg 3 RCTs (679/678) |
1 month | -37.9 (4.3) to -26.4 (37.2) | -28.4 (4.3) to -19.85 (29.8) | -9.21 (-10.63,-7.79) |
| 25 mg 2 RCTs (619/618) |
3 months | -30.73 (29.6) to -28.9 (40.2) | -23.13 (29.8) to -19.9 (40) | -8.1 (-11.86, -4.34) | |
| 50 mg 2RCTs (371/370) |
1 month | -35.8 (4.3) to -31.2 (29.6) | -28.4 (4.3) to -19.85 (29.8) | -8.73 (-12.39,-5.07) | |
| «Chalet FX, Luyet PP, Rabasa C, et al. Daridorexant...»2 | |||||
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Mean (SD) I | Mean (SD) C | Mean Difference (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: high I= intervention; C=comparison; CI=confidence interval |
|||||
| «Dutta S, Singhal S, Shah R, et al. Daridorexant as...»1 | 25mg 3 RCTs (679/678) |
1 month | 34.2 (48.9) to 56.2 (51.5) | 21.6 (48.9) to 52.7 (50.3) | 13.41 (8.13, 18.69) |
| 25 mg 2 RCTs (619/618) |
3 months | 47.8 (58.1) to 56.2 (56.9) | 37.1 (56.6) to 37.9 (58) | 14.55 (5.60, 23.49) | |
| 50 mg 2RCTs (371/370) |
1 month | 43.6 (48.7) to 77.4 (58.7) | 21.6 (48.9) to 52.7 (50.3) | 22.42 (15.27, 29.56) | |
| «Chalet FX, Luyet PP, Rabasa C, et al. Daridorexant...»2 | |||||
| Reference | Outcome and dose | Follow-up time | Absolute number of events I/All | Absolute number of events C/All | NNT (95% CI) |
|---|---|---|---|---|---|
| I= intervention; C=comparison; CI=confidence interval; WASO= wake after sleep onset; LPS= latency to persistent sleep | |||||
| «Chalet FX, Luyet PP, Rabasa C, et al. Daridorexant...»2 | WASO, 25mg | 1 month | 153/298 | 115/299 | 8 (5, 22) |
| WASO, 50mg | 1 month | 182/305 | 115/299 | 5 (4, 8) | |
| WASO, 25 mg | 3 months | 167/289 | 122/283 | 8 (5, 17) | |
| WASO, 50 mg | 3 months | 179/289 | 122/283 | 6 (4, 10) | |
| LPS, 25mg | 1 month | 202/298 | 157/299 | 7 (5, 14) | |
| LPS, 50mg | 1 month | 205/305 | 157/299 | 7 (5,15) | |
| LPS 25mg | 3 months | 200/289 | 175/283 | 15 (-148 to inf to 7) | |
| LPS 50mg | 3 months | 204/287 | 175/283 | 11 (6,74) | |