Table 1. Baseline characteristics of the included studies.
| Study | Dual orexin receptor antagonist (DORA) | Insomnia disorder diagnostic criteria | Total number of patients (n) | Patient interventions/PLA (n) | Duration of the treatment | Age groups in years | Age in years: mean(± SD) | ISI, Mean(± SD) | Pooled outcomes | Sleep parameter assessment tool |
|---|---|---|---|---|---|---|---|---|---|---|
| Herring et al. 14 (2016): trial 1 | SUV | DSM-4 | 1,021 | SUV 20/15 mg (254); SUV 40/30 mg (383); PLA (384) |
3 months | 18–64; ≥ 65 |
SUV 20/15 mg:* 55(± 16); SUV 40/30 mg:* 56(± 15); PLA: 56(± 15) |
SUV 20/15 mg:*: 16(± 4) SUV 40/30mg*: 16(± 4) PLA: 16(± 4) |
WASO at month 1; WASO at month 3; LPS at month 1; TST at month 3 - |
Electronic sleep diary; polysomnography |
| Herring et al. 14 (2016): trial 2 | SUV | DSM-4 | 1,009 | SUV 20/15 mg (239); SUV 40/30 mg (387); PLA (383) |
3 months | 18–64; ≥ 65 |
SUV 20/15 mg:* 56(± 16); SUV 40/30 mg:* 57(± 15); PLA: 57(± 15) |
SUV 20/15mg*: 17(± 4) SUV 40/30mg*: 16(± 4) PLA: 16(± 4) |
||
|
Michelson et al.
15
(2014) |
SUV | DSM-4 | 779 | SUV 30/40 mg (521); PLA (258) |
12 months | 18–64; ≥ 65 |
SUV 30/40 mg:* 61.3(± 14.5); PLA: 62.0(± 14.6) |
SUV 30/40mg*: 14.5(± 4.4) PLA: 16(± 4) |
WASO at month 1; WASO at month 12; TST at month 12 |
|
|
Black et al.
20
(2017) |
ALM | DSM-4 | 709 | ALM 100 mg (187); ALM 200 mg (177); ZOL 10 mg (168); PLA (177) |
2 weeks | 18–64 | ALM 100 mg: 44.1; ALM 200 mg: 46.1; ZOL 10 mg: 45.1; PLA: 46.2 |
NA | Mean WASO at weeks 1 and 2; mean LPS at weeks 1 and 2 |
Electronic sleep diary; polysomnography |
|
Fan et al.
16
(2017) |
SUV | DSM-4 | 120 | SUV 40 mg (60); PLA (60) |
6 months | 18–64 | SUV 40 mg: 50.6(± 11.9); PLA: 51.4(± 12.2) |
SUV 40mg: 14.3(± 4.0) PLA: 14.1(± 3.9) |
TST at month 6 | Electronic sleep diary |
|
Rosenberg et al.
23
(2019): SUNRISE 1 |
LEM | DSM-5 | 1,006 | LEM 5 mg (266);LEM 10 mg (269); ZOL 6.5 mg (263); PLA (208) |
1 month | ≥ 55 to < 65; ≥ 65 |
LEM 5 mg: 63.7(± 6.8); LEM 10 mg: 64.2(± 6.9); ZOL 6.5 mg: 64.3(± 7.1); PLA: 63.9(± 6.8) |
LEM 5mg: 18.9(± 3.5) LEM 10mg: 19.0(± 3.3) ZOL 6.5mg 19.2(± 3.5) PLA: 19.4(± 3.6) |
WASO at month 1 (nights 29 and 30) | Polysomnography |
| Dauvilliers et al. 21 (2019) | DAR | DSM-5 | 359 | DAR 5 mg (60); DAR 10 mg (58); DAR 25 mg (60); DAR 50 mg (61); ZOL 10 mg (60); PLA (60) |
1 month | 18–64 | DAR 5 mg: 42.4(± 11.4); DAR 10 mg: 45.2(± 10.9); DAR 25 mg: 46.4(± 11.9); DAR 50 mg: 45.0(± 11.5); ZOL 10 mg: 43.7(± 11.8); PLA: 45.7(± 10.4) |
DAR 5mg: 20.8(± 2.6) DAR 10mg: 21.2(± 3.3) DAR 25mg: 21.3(± 2.7) DAR 50 mg: 21.1(± 2.7) ZOL 10 mg: 21.3(± 2.9) PLA: 21.3(± 2.7) |
WASO at month 1 (week 4); LPS (days 1 and 2) |
Electronic sleep diary; polysomnography |
|
Kärppä et al.
18
(2020)
SUNRISE 2 |
LEM | DSM-5 | 949 | LEM 5 mg (316); LEM 10 mg (315); PLA (318) |
6 months | < 65; ≥ 65 to < 75; ≥ 75 |
LEM 5mg: 54.2(± 13.7) LEM 10mg: 54.8(± 13.7) PLA: 54.5(± 14.0) |
LEM 5 mg: 19.6(± 3.3); LEM 10 mg: 19.1(± 3.4); PLA: 19.0 |
WASO at month 6; TST at month 6 |
Electronic sleep diary |
| Mignot et al. 22 (2022): trial 1 | DAR | DSM-5 | 930 | DAR 25 mg (310); DAR 50 mg (310); PLA (310) (3.1) |
3 months | 18- 64; ≥ 65 |
DAR 25mg: 55.8(± 15.3) DAR 50mg: 55.5(± 15.3) PLA: 55.1(± 15.4) |
DAR 25 mg: 19.0(± 4.3); DAR 50 mg: 19.3(± 4.0); PLA: 19.2(± 4.0) |
WASO at month 1; WASO at month 3; LPS at month 1; TST at month 3 - |
Electronic sleep diary; polysomnography |
| Mignot et al. 22 (2022): trial 2 | DAR | DSM-5 | 924 | DAR 10 mg (307); DAR 25 mg (309); PLA (308) |
3 months | 18- 64; ≥ 65 |
DAR 10 mg: 57.1(± 14.0); DAR 25 mg: 56.3(± 14.4); PLA: 56.7(± 14.1) |
DAR 10 mg: 19.9(± 3.8); DAR 25 mg: 19.5(± 4.0); PLA: 19.6(± 4.1) |
Abbreviations: ALM, almorexant; DAR, daridorexant; DSM, Diagnostic and Statistical Manual of Mental Disorders; ISI, Insomnia Severity Index; LEM, lemborexant; LPS, latency to persistent sleep; NA, not available; PLA, placebo; SD, standard deviation; SUV, suvorexant; TST, total sleep time; WASO, wake time after sleep onset; ZOL, zolpidem.
Notes: *Dosing according to age group, with higher doses for non-elderly individuals and lower doses for elderly individuals; ISI: 0–7 = no clinically significant insomnia; 8–14 = subthreshold insomnia; 15–21 = clinical insomnia (moderate severity); 22–28 = clinical insomnia (severe).