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.

Polifarmácia e cognição em pacientes com idade avançada / Polypharmacy and cognition in elderly patients

Objetivo: Avaliar a prevalência da polifarmácia e da prescrição de medicações inapropriadas, bem como suas associações com a capacidade cognitiva e funcional do idoso. Métodos: Estudo observacional transversal, no qual foram analisadas as medicações prescritas em 141 prontuários para pacientes acima de 50 anos, em associação com testes que quantificaram a capacidade funcional e cognitiva deles. Resultados: Observou-se média de 4,41 medicamentos por paciente, sendo que 0,41 deles foram considerados inapropriado, segundo o critério de Beers. Verificou-se também relação estatisticamente significativa quanto ao número de medicações e testes que mediam a capacidade funcional e cognitiva dos idosos. Conclusão: O aumento da polifarmácia e da prescrição de medicações potencialmente inadequadas acarretou significativa piora da capacidade cognitiva e funcional do idoso

Objective: To evaluate the prevalence of polypharmacy and of the prescription of inappropriate medications, as well as their associations with the cognitive and functional capacity of the elderly. Methods: Cross-sectional observational study which analyzed the drugs prescribed in 141 medical records for patients over 50 years of age, associated with tests that quantified their functional and cognitive capacity. Results: An average of 4.41 medications per patient was observed, and 0.41 were considered inappropriate according to the Beers criteria. There was also a statistically significant relation regarding the number of medications and tests that measure the functional and cognitive capacity of the elderly. Conclusion: The increase in polypharmacy and in the prescription of potentially inappropriate medications led to a significant impairment of the cognitive and functional capacity of the elderly

Effects of zolpidem and zaleplon on cognitive performance after emergent morning awakenings at Tmax: a randomized placebo-controlled trial.

STUDY OBJECTIVES: Prescription sleep aids are frequently used in the general population and even more frequently in spaceflight. To evaluate the risk to operational safety, a ground-based, double-blind, placebo-controlled study on the emergent awakening effects of zolpidem and zaleplon was conducted. METHODS: N = 34 participants (age M = 42.1 ± 9.7; 25 males; 9 Astronauts, 7 Astronaut candidates, and 18 Flight Controllers) were investigated for three nights separated by M = 10 days. They were randomized to ingestion of one of the following at lights out: placebo, 10 mg zaleplon, and either 5 mg (N = 20) or 10 mg (N = 14) zolpidem. They were awakened abruptly by alarm at the expected PK,max (1 hr after lights out for zaleplon; 1.5 hr for placebo/zolpidem). Participants were required to turn off the alarm and perform a cognitive test battery twice, separated by a 20-30 min reading break. They then returned to sleep and were awakened to perform the same cognitive tasks at an average of 6.7 hr after drug ingestion. RESULTS: Relative to placebo, the effects of 10 mg zaleplon and 5 mg zolpidem on cognitive performance were minor. In contrast, 10 mg zolpidem adversely affected cognitive throughput (p < 0.001), psychomotor vigilance (p < 0.001), working memory (p < 0.01), delayed word recall (p < 0.05), and subjective sleepiness (p < 0.01) at the first emergent awakening. At terminal awakening, neither cognitive performance nor subjective sleepiness was impaired after ingestion of zaleplon or zolpidem (5 mg and 10 mg) compared with placebo. CONCLUSIONS: Presleep ingestion of sleep medications, especially 10 mg zolpidem, poses a risk for performance errors after emergent awakenings near the expected PK,max. REGISTRATION: Optimize Astronaut Sleep Medication Efficacy and Individual Effects (clinicaltrials.gov ID NCT03526575).