Table 6 GRADE summary of findings
Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
|---|---|---|---|---|---|---|
Risk with placebo | Risk with BDLM | |||||
Mortality | 0 per 1000 | 0 per 1000 (0 to 0) | not estimable | (0 studies) | – | Mortality was not assessed in any of the studies |
Hospitalization assessed with: number of cases with hospitalization for traumatic brain injury and hip fractures timing of exposure: 30 days | 20,103 cases 142,059 controls (3 observational studies) (80–82) | – | Tom 2016 showed an OR of 1.87 (CI95 1.56–2.25) for hospitalization for traumatic brain injury in Zolpidem users vs. non-users. ORs were 0.67 (CI95 0.40–1.13) for Eszopiclone and 0.85 (CI95 0.21–3.34) for Zaleplon. Hospitalization for hip fracture was investigated by Tom 2016, Wang 2001 and Zint 2010. ORs for Zolpidem were 1.59 (CI95 1.41–1.79), 1.95 (CI95 1.09–3.51) and 1.26 (CI95 1.11–1.44), for Eszopiclone 1.12 (CI95 0.83–1.50), and for Zaleplon 0.92 (CI95 0.40–2.13). | |||
Quality of life (Eszopiclone vs. placebo) assessed with: SF-36 follow up: mean 12 weeks | The mean quality of life (Eszopiclone vs. placebo) was 68.5 | mean 71.6 higher (0 to 0) | – | 388 (1 RCT) (66) | ⨁⨁⨁◯ MODERATE a | Score for General health provided (p = 0.009). Score for vitality also better for Eszopiclone [58.9 (21.2 vs. 55.1 (20.3), p = 0.008], all other SF-36-scores (domains) no significant differences. |
Accidental event assessed with: events follow up: mean 3 months | 1 per 1000 | 1 per 1000 (0 to 10) | OR 2.77 (0.38 to 19.76) | 157,975 (1 observational study) (83) | ⨁⨁⨁⨁ HIGH | The adjusted OR was 1.48, p < 0.05, 95% CI not provided. |
Hip fracture with Zolpidem assessed with: events timing of exposure: range 1 days to 180 days | 98 per 1000 | 140 per 1000 (94 to 203) | OR 1.50 (0.96 to 2.34) | 4307 cases 17,115 controls (3 observational studies) (78, 81,82) | ⨁⨁⨁⨁ HIGH | There were three more studies evaluating fracture risk which could not be included in the meta-analysis. Tom 2016 showed an increased hip fracture risk for Zolpidem, OR 1.59 (CI95 1.41–1.79), but not for Eszopiclone and Zaleplon. Lai 2015 revealed an increased hip fracture risk for Zopiclone, aOR 3.56 (CI95 2.33–4.84), Berry 2013 showed an increases hip fracture risk for all Z-substance users, OR 1.66 (CI95 1.45–1.90). (74, 77, 80) |
Any fracture with Zolpidem assessed with: events timing of exposure: mean 1 days | 82 per 1000 | 99 per 1000 (83 to 117) | OR 1.22 (1.01 to 1.48) | 7518 cases 30,072 controls (2 observational studies) (76, 79) | ⨁⨁⨁⨁ HIGH | Tang 2015 provides an adjusted OR of 1.13 (CI95 0.96–1.34) and Kang 2012 an adjusted OR of 1.72 (CI95 1.37–2.16). |
Falls assessed with: events timing of exposure: mean 1 days | 48 per 1000 | 108 per 1000 (50 to 217) | OR 2.38 (1.04 to 5.43) | 165 cases 165 controls (1 observational study) (75) | ⨁⨁⨁◯ MODERATEb | Results are based on only one case-control-study with high risk of bias. |
Effect “well-rested” assessed with: sleep quality 11-point Likert scale Eszopiclone 2 mg vs Placebo Scale from: 0 to 11 follow up: 12 weeks | – | SMD 7.1 SD higher (0 to 0) | – | 159 (1 RCT) (73) | – | |