The efficacy and safety of zolpidem and zopiclone to treat insomnia in Alzheimer's disease: a randomized, triple-blind, placebo-controlled trial.

No prior studies have evaluated the efficacy and safety of zolpidem and zopiclone to treat insomnia of demented patients. This randomized, triple-blind, placebo-controlled clinical trial used these drugs to treat patients with probable, late onset Alzheimer's dementia (AD) (DSM V and NINCDS-ADRDA criteria) exhibiting insomnia (DSM V criteria and nocturnal NPI scores ≥ 2). Actigraphic records were performed for 7 days at baseline and for 14 days during the treatment period in 62 patients aged 80.5 years in average and randomized at a 1:1:1 ratio for administration of zolpidem 10 mg/day, zopiclone 7.5 mg/day or placebo. Primary endpoint was the main nocturnal sleep duration (MNSD), whereas secondary outcomes were the proportion of the night time slept, awake time after sleep onset (WASO), nocturnal awakenings, total daytime sleep time and daytime naps. Cognitive and functional domains were tested before and after drug/placebo use. Three participants under zopiclone use had intervention interrupted due to intense daytime sedation and worsened agitation with wandering. Zopiclone produced an 81 min increase in MNSD (95% confidence interval (CI): -0.8, 163.2), a 26 min reduction in WASO (95% CI: -56.2, 4.8) and a 2-episode decrease in awakening per night (95% CI: -4.0, 0.4) in average compared to placebo. Zolpidem yielded no significant difference in MNSD despite a significant 22 min reduction in WASO (95% CI: -52.5, 8.3) and a reduction of 1 awakening each night (95% CI: -3.4, 1.2) in relation to placebo. There was a 1-point reduction in mean performance in the symbols search test among zolpidem users (95% CI: -4.1, 1.5) and an almost eight-point reduction in average scores in the digit-symbol coding test among zopiclone users (95% CI: -21.7, 6.2). In summary, short-term use of zolpidem or zopiclone by older insomniacs with AD appears to be clinically helpful, even though safety and tolerance remain issues to be personalized in healthcare settings and further investigated in subsequent trials. This trial was registered in ClinicalTrials.gov Identifier: NCT03075241.

Zopiclone to treat insomnia in older adults: A systematic review.

Considering the global increase in use of Z-drugs to treat insomnia, the study objective was to conduct a systematic review on the efficacy and safety of zopiclone to treat sleep disorders in older adults compared to other sedative-hypnotics, to placebo or to non-pharmacological interventions. The literature search for original reports - clinical trials, cohort studies and cross-sectional, observational investigations - was done in eleven databases and web search engines followed PRISMA guidelines, and methodological quality was assessed using the Risk of Bias tool in the Cochrane Reviewers' Handbook. The search resulted in 12 randomized, placebo-controlled clinical trials along with 2 open studies and 2 observational reports. Overall, the studies suggest that zopiclone is effective to treat insomnia by reducing sleep latency, nocturnal awakenings and wake time after sleep onset while increasing total sleep time, with probable effects on sleep architecture. Zopiclone was found to be fairly tolerated, to induce a low rate of adverse events with non-severe impact on psychomotor or cognitive performance and to produce no major harm to the overall well-being and daily living abilities. However, the quality of most studies was classified as low or unclear. Though the studies available support benefits from zopiclone use, there is still a need for further evidence on long-term effects, tolerability and safety in the treatment of older adults by means of high-quality trials.

More than a quarter century of the most prescribed sleeping pill: Systematic review of zolpidem use by older adults.

Zolpidem is widely used to treat insomnia of older adults despite that few randomized controlled studies were conducted in this group. We systematically reviewed the relevant literature on efficacy/effectiveness and safety of zolpidem use by elderly individuals in relevant databases completed with a manual search of key journals. Studies were required to include individuals aged ≥60 years under intervention with zolpidem compared to placebo or other hypnosedatives. Outcomes were either objectively- or subjectively-assessed improvements in specific sleep parameters and safety for clinical use. The 31 reports selected for review were mostly of low-quality. The evidence suggests that zolpidem is useful typically by reducing sleep latency and episodes of wake after sleep onset, and increasing total sleep time and sleep efficiency. Regarding safety and tolerability, analyses suggest a low risk of daytime sleepiness and of deleterious effects on memory or psychomotor performance, provided that recommended dosage and precautions are followed. Few retrospective studies associate zolpidem use with risk of falls, fractures, dementia, cancer, and stroke. Zolpidem appears effective at lower doses and for short-term treatment among the elderly. Rigorous, new clinical trials are warranted to further document the specific effects of zolpidem in older individuals.