Authors and publication year | Study design | Aim | Sample size and number/percentage of patients > 65 years | Study duration or follow-up | Outcome | Sponsor |
---|---|---|---|---|---|---|
Ancoli-Israel et al. 2010 (66) | Randomized, placebo-controlled, double-blind study | To evaluate the efficacy and safety of 12 weeks of nightly eszopiclone in elderly outpatients with insomnia | n = 194 Eszopiclone 2 mg n = 194 placebo | 2-week single-blind placebo assessment period 12-week treatment 2-week single-blind placebo run-out 2-week no drug follow-up | Sleep parameters Daytime function parameters Insomnia severity index (ISI) ADE | Sepracor INC., Marlborough, MA |
Ancoli-Israel et al. 1999 (67) | Multicenter, randomized, placebo-controlled double-blind study | To evaluate the efficacy and safety of Zaleplon 5/10 mg in elderly outpatients with insomnia in comparison to Zolpidem 5 mg and placebo | n = 166 Zaleplon 5 mg n = 165 Zaleplon 10 mg n = 111 Zolpidem 5 mg n = 107 placebo | 1-week single-blind placebo baseline period 2-week double-blind treatment 1-week single-blind placebo run-out | Sleep parameters Rebound insomnia ADE Routine physical examination (vital signs, ECG) | Wyeth-Ayerst Research, Radnor, Pa. and Zaleplon clinical study group |
Avidan et al. 2010 (83) | Retrospective cohort analysis | To examine the risk of accidental events in older adults newly prescribed Benzodiazepine-like medication (BDLM) or selective melatonin receptor agonist (MRA) | n = 156,987 Benzodiazepine-like medication (Zolpidem, Zaleplon, Eszopiclone) n = 988 Selective melatonin receptor agonist (Ramelteon) | 30 days of insomnia therapy and 3-month period after treatment initiation | Accidental events identified using External Causes of Injury Codes (ICD) and ICD-9-CM Codes in claims files | Takeda pharmaceutical company, Ltd |
Berry et al. 2013 (74) | Case-crossover study | To estimate the association between BDLM use (Zolpidem, Eszopiclone, Zaleplon) and the risk for hip fractures among a nationwide sample of long-stay nursing home residents | n = 927 with discordant Exposure to BDLM in hazard and control periods | Dispensing of BDLM (Zolpidem, Eszopiclone, Zaleplon) 30 days before fracture (hazard period) or 60–90 days and 120–149 days before fracture (control periods) | Hip fracture defined as ICD-9: 820.xx or 733.14 | National Institute on Aging and Friends of Hebrew Senior Life |
Chang et al. 2011 (75) | Case-control study | To examine the association between medical conditions and medications and falls in older people in hospital | n = 19 Zolpidem n = 8 controls | Medications used within 24 h of falls | Falls reported in the hospital | Department of Health, Taiwan |
Dehlin et al. 1995 (68) | Multicenter, randomized, double-blind study | To compare the efficacy and safety of Zopiclone 5 mg and Flunitrazepam 1 mg in elderly patients | n = 50 Zopiclone 5 mg n = 52 Flunitrazepam 1 mg | 3-day single-blind placebo baseline period 2-week double-blind treatment 1-week single-blind placebo run-out | Sleep parameters Daytime function parameters ADE | Rhone-Poulenc Rorer, Box 33, Helsingborg Sweden |
Elie et al. 1990 (69) | Randomized, placebo controlled, double-blind study | To evaluate and compare the efficacy and safety of Zopiclone 5/7.5 mg and Triazolam 0.125/0.25 mg in elderly patients with insomnia in comparison with placebo | n = 15 Zopiclone 5 mg for 1 week then increase to 7.5 mg for 2 weeks n = 14 Triazolam 0.125 mg for 1 week then increase to 0.25 mg for 2 weeks n = 15 placebo | 3-day single-blind wash-out period 3-week double-blind treatment period 4-day single-blind wash-out period | Sleep parameters Hang-over Routine physical examination (ECG, routine lab test) ADE | Rhone-Poulenc Pharma Inc., Montreal, CA |
Kang et al. 2012 (76) | Case-crossover study | To evaluate the risk of fractures related with Zolpidem in elderly insomnia patients | n = 1508 with discordant exposure to BDLM in hazard and control periods | Prescription of Zolpidem 1 day before fracture (hazard period) or 1 day before 5/10/15 and 20 weeks before fracture (control periods) | Diagnosis of fracture ICD-10: S02, S12, S22, S32, S42, S52, S62, S72, S82, S92, T02 | No information |
Klimm et al. 1987 (70) | Randomized double-blind study | To evaluate the efficacy and safety of Zopiclone 7.5 mg in elderly patients with insomnia in comparison to Nitrazepam 5 mg | n = 36 Zopiclone 7.5 mg n = 36 Nitrazepam 5 mg | 1-week single-blind placebo wash-out period 1-week double-blind treatment | Sleep parameters Spiegel Sleep Questionnaire ADE General evaluation | No information |
Lai et al. 2015 (77) | Case-control study | To investigate the correlation between zopiclone use and risk of hip fracture in elderly adults | Cases: n = 170 Zopiclone last 7 days n = 780 Zopiclone before n = 10,046 non-users Controls: n = 37 Zopiclone last 7 days n = 586 late users n = 8458 non-users | Prescription of Zopiclone: − 7 days prior to fall -any time before -never | First episode of hip fracture according to ICD 9 | Taiwan Ministry of Health and Welfare Clinical Trial Research Center of Excellence, China Medical University Hospital Academia Sinica of the Taiwan Biobank Stroke Biosignature Project of the National Research Program for Biopharmaceuticals Stroke Clinical Trial Consortium, Taiwan Tseng-Lien Lin Foundation, Taiwan Tai- wan Brain Disease Foundation, Taiwan Katsuzo and Kiyo Aoshima Memorial Funds, Japan |
Leppik et al. 1997 (71) | Randomized, placebo-controlled double-blind study | To evaluate the efficacy and safety of Zolpidem 5 mg, Triazolam 0.125 mg and Temazepam 15 mg in elderly patients with insomnia in comparison with placebo | n = 76 Zolpidem 5 mg n = 71 Triazolam 0.125 mg n = 74 Temazepam 15 mg n = 74 placebo | 1-week single-blind placebo wash-out period 4-week double-blind treatment | Sleep parameters Daytime function parameters Global Impression of Therapy score ADE Routine physical examination (ECG, laboratory evaluation) | Lorex Pharmaceuticals, Skokie, IL |
Pierfitte et al. 2001 (78) | Case-control study | To determine whether benzodiazepines are associated with an increased risk of hip fracture | Cases: Zolpidem n = 15 Zopiclone n = 14 Controls: Zolpidem n = 35 Zopiclone n = 48 | Drug use 24 h before fracture determined from questionnaires, medical records, or blood samples | Acute hip fracture resulting from a fall, not associated with cancer, a traffic accident, or aggression, ascertained from x-ray films and orthopedic consultation | Agence du médicament, Paris Department of Pharmacology, Victor Segalen University, Bordeaux, France |
Roger et al. 1993 (72) | Randomized placebo- controlled double-blind multicenter study | To compare the efficacy and safety of Zolpidem with a reference benzodiazepine in elderly insomniac patients | n = 70 Zolpidem 5 mg n = 74 Zolpidem 10 mg n = 77 Triazolam 0.25 mg | 3-day placebo wash-out period 3-week double-blind treatment period 7-day placebo withdrawal period | Sleep parameters Use of rescue hypnotic medication ADE | No information |
Scharf et al. 2005 (73) | Randomized placebo- controlled double-blind multicenter study | To evaluate the efficacy of Eszopiclone and primary insomnia | n = 72 Eszopiclone 1 mg n = 79 Eszopiclone 2 mg n = 80 placebo | 2-week double-blind treatment period | Sleep parameters Daytime function parameters Q-LES-Q ADE Routine physical examination (ECG, vital signs, neurological examination, lab measures) | Sepracor, Inc., Marlborough, Mass., US |
Tang et al. 2015 (79) | Case-crossover study | To clarify the risk of acute effects of Zolpidem on all-sites of fracture in the elderly | n = 6010 with discordant exposure to BDLM in hazard and control periods | 1 day prior to fracture (hazard period) or 1 day 5/10/15/20 weeks prior to fracture (control periods) | ICD-9 CM: 820, 812, 813, 814, 805, 806, 800–829 | Tri-Service-General-Hospital Ministry of Science and Technology of Taiwan National Chiao Tung University Ministry of Education of Taiwan |
Tom et al. 2016 (80) | Case-crossover study | To test the hypothesis that use of Zolpidem, Eszopiclone, and Zaleplon would be associated with increased risk of traumatic brain injury (TBI) and hip fracture | TBI: BDLM users n = 491 non-BDLM users n = 14,540 Hip fracture: BDLM users n = 1192 non-BDLM users n = 36,641 | 30 days before fracture (hazard period) or 3/6/9/12 months before fracture (control periods) | ICD-9 CM: 800.xx, 801.xx, 803.xx, 804.xx, 850.xx-854.1x, 950.1–950.3, 959.01; 820.xx | National Institute of Health |
Wang et al. 2001 (81) | Case-control study | To identify hazardous regimens (for insomnia) that should be avoided and safer regimens that may be used preferentially by older people | n = 20 Zolpidem n = 35 controls | Index date and 6 months prior | Hospitalization for surgical repair of hip fracture | National Institute of Drug Abuse National Institute on Aging |
Zint et al. 2010 (82) | Case-control study | To determine how concomitant use of potentially interacting drugs, drug dosage, and duration of therapy modify the risk of hip fracture associated with use of BDLM in older adults | Cases: Zaleplon n = 21 Zolpidem n = 456 Controls: Zaleplon n = 62 Zolpidem n = 1608 | 14 days before fracture | First hip fracture leading to hospitalization | Graduiertenkolleg 793 National Institute on Aging of the National Institutes of Health Federal Ministry of Education and Research |