Short-term use of benzodiazepine receptor agonists among the working-age population)
Näytönastekatsaukset
2.6.2026
Level of evidence: B
Compared to placebo benzodiazepine receptor agonists zolpidem and zopiclone probably reduce insomnia symptoms during short-term use (<4 weeks) among the working-age population with insomnia disorder.
Compared to placebo intervention groups had somewhat more discontinuation due to adverse events, but serious adverse events were sparse until the end of follow-up. The applicability of interventions in Finnish population is good.
| Reference | Study type | Population | Intervention and comparison | Outcomes | Risk of bias [ « Additional comments for included studies»2 Additional comments] |
|---|---|---|---|---|---|
| RCT=randomized controlled trial; SR=systematic review; MA=meta-analysis; PBO=placebo | |||||
| «Yue JL, Chang XW, Zheng JW, et al. Efficacy and tolerability of pharmacological treatments for insomnia in adults: A systematic review and network meta-analysis. Sleep Med Rev 2023;68():101746 »1 | Systematic review and network meta-analysis. PBO-controlled or head-to-head RCTs. | Adults (≥18 years) having primary insomnia 69 studies were included (17319 patients) during 1998-2022. | 20 drugs including zolpidem 6.25-12.5mg (22 studies) and zopiclone 7.5mg (4 studies) vs. PBO or other active comparator. | Primary outcomes: sleeplatency (SL), awake time after sleep onset (WASO), discontinuation for adverse events (AED) Secondary outcomes: total sleep time (TST), sleep efficiency (SE), sleep quality (SQ), adverseevents (ADE). | Moderate |
| «De Crescenzo F, D'Alò GL, Ostinelli EG, et al. Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and netwo»2 | Systematic review and network meta-analysis | Adults (≥18 years) with insomnia disorder. 170 trials for the SR and 154 RCTs (30 interventions and 44089 participants) | 36 interventions including zolpidem 3.5-15mg (22 studies) and zopiclone 3.75-15mg (2 studies) vs. PBO or active comparator | Primary outcomes: subjective efficacy, AED, ADE Secondary outcomes: SL, WASO, TST, Number of awakenings (both PSG and questionnaire), symptoms of hangover or sedation, rebound symptoms, any AE and serious AEs. | Low |
| Reference | Comments |
|---|---|
| «Yue JL, Chang XW, Zheng JW, et al. Efficacy and tolerability of pharmacological treatments for insomnia in adults: A systematic review and network meta-analysis. Sleep Med Rev 2023;68():101746 »1 | Inclusion criteria: primary diagnosis of insomnia according to the Diagnostic and Statistical Manual of Mental Disorders (DSM), the International Statistical Classification of Diseases and Related Health Problems (ICD), or International Classification of Sleep Disorders (ICSD) Sensitivity analyses were performed. The trial was registered in PROSPERO. The review was performed in accordance with PRISMA guidelines. Risk of bias was assessed with the Cochrane Collaboration's risk of bias tool (RoB tool). The confidence in evidence of the primary outcomes was estimated by the Confidence in Network Meta-Analysis (CINeMA) framework and web application, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework for network meta-analyses. The risk of bias for blinding-therapist was high in 30.4% of studies, and the risk of bias for allocation was unclear in 49.3% of studies. In Zolpidem vs. PBO studies there was major concerns due to heterogeneity and the confidence rating was considered low or moderate. In Zopiclone vs PBO studies there was major concerns due to imprecision and incoherence, and the confidence rating was considered very low. The quality of sleep was measured by any self-rated scale. Subanalyses were performed separately to age-groups < or > 60 years and durations < or > 4 weeks for SL, WASO and AED. Authors did not report which studies were included in the subanalyses, hence accurate follow-up time was not known. |
| «De Crescenzo F, D'Alò GL, Ostinelli EG, et al. Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and netwo»2 | The confidence in evidence of the primary outcomes was estimated by the Confidence in Network Meta-Analysis (CINeMA) framework. Literature searches were performed until November 2021. For the analysis of acute outcomes, data after 4 weeks was used. If it was not available, data ranging between 1-12 weeks was used. Risk of bias of individual studies was assessed with the Cochrane risk of bias tool. Subgroup analyses were perfomed in the age groups 18-65 years and > 65 years. Authors did not report which studies were included in the subanalyses, hence accurate follow-up time was not known. |
Results
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Relative effect SMD (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: moderate The quality of evidence is downgraded due to study limitations. I= intervention; C=comparison; CI=confidence interval | |||||
| «Yue JL, Chang XW, Zheng JW, et al. Efficacy and tolerability of pharmacological treatments for insomnia in adults: A systematic review and network meta-analysis. Sleep Med Rev 2023;68():101746 »1 | NR | NR | NR | ||
| «De Crescenzo F, D'Alò GL, Ostinelli EG, et al. Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and netwo»2 | 22 studies 2 studies | 4 weeks | NR | NR | Zolpidem: 0.42 (0.30; 0.55) Zopiclone: 0.60 (0.35; 0.85) |
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Relative effect SMD (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: low The quality of evidence is downgraded due to study limitations and imprecision. I= intervention; C=comparison; CI=confidence interval; MD=mean difference | |||||
| «Yue JL, Chang XW, Zheng JW, et al. Efficacy and tolerability of pharmacological treatments for insomnia in adults: A systematic review and network meta-analysis. Sleep Med Rev 2023;68():101746 »1 | < 60 years, 18 studies All age groups, 12 studies | All durations < 4 weeks | NR NR NR NR | NR NR NR NR | Zolpidem: -0.70 (-1.42, 0.02) Zopiclone: -0.24 (-1.70, 1.23) Zolpidem: NR Zopiclone: -0.27 (-1.69, 1.16) |
| «De Crescenzo F, D'Alò GL, Ostinelli EG, et al. Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and netwo»2 | NR | ||||
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Relative effect SMD (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: low The quality of evidence is downgraded due to study limitations and imprecision. I= intervention; C=comparison; CI=confidence interval | |||||
| «Yue JL, Chang XW, Zheng JW, et al. Efficacy and tolerability of pharmacological treatments for insomnia in adults: A systematic review and network meta-analysis. Sleep Med Rev 2023;68():101746 »1 | < 60 years, 25 studies All age groups, 12 studies | All durations < 4 weeks | NR NR NR NR | NR NR NR NR | Zolpidem: -1.22 (-2.07; -0.37) Zopiclone: -0.51 (-2.60; 1.59) Zolpidem: -2.17 (-3.74; -0.60) Zopiclone: NR |
| «De Crescenzo F, D'Alò GL, Ostinelli EG, et al. Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and netwo»2 | NR | ||||
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Odds Ratio (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: moderate The quality of evidence is downgraded due to (study limitations, imprecision). I= intervention; C=comparison; CI=confidence interval | |||||
| «Yue JL, Chang XW, Zheng JW, et al. Efficacy and tolerability of pharmacological treatments for insomnia in adults: A systematic review and network meta-analysis. Sleep Med Rev 2023;68():101746 »1 | < 60 years, 12 studies All age groups, 6 studies | All durations < 4 weeks | NR NR NR NR | NR NR NR NR | Zolpidem: 1.95 (1.32; 2.9) Zopiclone: NR Zolpidem: 2.4 (0.09; 64.99) Zopiclone: NR |
| «De Crescenzo F, D'Alò GL, Ostinelli EG, et al. Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and netwo»2 | 19 studies 5 studies | 4 weeks | NR NR | NR NR | Zolpidem: 2.29 (1.55; 3.39) Zopiclone: 2.66 (1.58; 4.47) |
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Odds ratio (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: moderate The quality of evidence is downgraded due to study limitations. I= intervention; C=comparison; CI=confidence interval | |||||
| «Yue JL, Chang XW, Zheng JW, et al. Efficacy and tolerability of pharmacological treatments for insomnia in adults: A systematic review and network meta-analysis. Sleep Med Rev 2023;68():101746 »1 | 69 studies were included (17319 patients) | NR | NR | Zolpidem 1.34 (1.08; 1.65) Zopiclone 1.42 (0.84; 2.40) | |
| «De Crescenzo F, D'Alò GL, Ostinelli EG, et al. Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and netwo»2 | 86 trials (27 interventions; 26543 participants) (all age-groups included) | Until the end of the follow-up | NR | NR | Zolpidem 1.27 (1.10; 1.47) Zopiclone 1.60 (1.28; 2.01) |
References
- Yue JL, Chang XW, Zheng JW, et al. Efficacy and tolerability of pharmacological treatments for insomnia in adults: A systematic review and network meta-analysis. Sleep Med Rev 2023;68():101746 «PMID: 36701954»PubMed
- De Crescenzo F, D'Alò GL, Ostinelli EG, et al. Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis. Lancet 2022;400(10347):170-184 «PMID: 35843245»PubMed