We retrospectively analyzed nocturnal fall risk associated with individual sleep medications to investigate effects of individual hypnotic drugs on the occurrence of nocturnal falls in older adults. Falls have been reported to occur in patients with various internal and external risk factors [10]. In particular, the relationship between age and fall frequency has been reported as 27% for those aged ≥ 65 years and > 50% for those aged ≥ 80 years living in long-term care facilities, indicating fall risk significantly increases with age [11–14]. Therefore, when prescribing hypnotic drugs for older adults, one should consider drugs that are unlikely to increase fall risk. In this study, we used the PS matching method to homogenize patient backgrounds to analyze effects of specific hypnotic drugs in detail, considering relationships among multiple risk factors for falls. A comparison between groups of patients who did and did not experience nocturnal falls before PS matching revealed significant differences in 10 factors considered. However, no significant differences were found regarding any items except sleeping pill use after PS matching. Further, between-group comparisons of fall risk associated with each sleeping medication after PS matching revealed significant differences only when benzodiazepine receptor agonists were considered. This finding suggests that benzodiazepine receptor agonists may increase fall risk in older adults.
A meta-analysis of observational studies of older subjects aged ≥ 65 years previously suggested that benzodiazepine receptor agonists significantly increase fall incidence, regardless of the duration of drug action [15]. In older adults, blood levels of drugs may be increased because of the impairment of renal and hepatic function associated with physiological decline, which likely increases fall risk. This study is consistent with European STOPP/START criteria that indicate that use of benzodiazepine receptor agonists in older adults (those aged > 65 years) is inappropriate because of increased risk of falls and fractures [16]. However, results of the present analysis suggest that melatonin receptor agonists and orexin receptor antagonists are safer than benzodiazepine receptor agonists for use in older adults with regard to fall risk. Melatonin receptor agonists and orexin receptor antagonists have been shown to improve insomnia, reduce balance impairment, and prevent delirium, suggesting that they are safe for use in older adults in terms of fall risk [17–21]. Furthermore, a recent case-crossover study of hospitalized patients aged ≥ 75 years in Japan reported that among hypnotic drugs, benzodiazepine receptor agonists increased risk of falls, whereas melatonin receptor agonists and orexin receptor antagonists did not [22]; these results are consistent with those of the present study.
In the present analysis of fall risk associated with each hypnotic drug, the population was limited to older persons aged ≥ 65 years at high risk of falling, and cases of concomitant use of sleep medications were excluded. In addition, this study homogenized patient backgrounds using PS matching, a method not widely used to assess fall risk among the population considered. By adjusting for multiple confounding factors, we believe that our study more carefully assessed fall risk in patients taking hypnotic drugs than did other studies, thereby strongly supporting the previously reported association between falls and hypnotic drug use in older adults.
A multivariate analysis with 24 extraction factors (excluding hypnotic drug use) was performed in this study. Results revealed significant odds ratios for the following five factors: age, male sex, fall in the past 6 months, advanced recurrent malignancies, and analgesic agent use. Age and sex were reported in a previous study. Recently, fall history was reported as a risk factor for recurrent falls [23]. Further, patients with malignant tumors have been reported to be at an increased risk of falling owing to muscle weakness and poor balance due to malignant tumors and treatment such as chemotherapy and surgery [24].
As this was a retrospective study conducted in a single facility, there may be a bias regarding patient background. Additionally, sleeping pill dosage was not examined, which may have been a confounding factor. However, results of this study are consistent with those reporting effects of hypnotic drugs thus far. Further, current data clarify the association between nighttime falls and hypnotic drugs in older adults.
The present study did show that patients with advanced recurrent malignancies were at the highest risk of falls. This finding indicates that when sleep medication is used in these patients, benzodiazepine receptor agonists should be avoided, while orexin receptor antagonists and melatonin receptor agonists, which do not increase risk of falls, should be considered. The results of this study suggest that benzodiazepine receptor agonists are risk factors for falls in older adults. In contrast, orexin receptor antagonists and melatonin receptor agonists can be safely used in older adults in terms of fall risk. In particular, the high risk of falling among older patients, especially those with advanced recurrent malignancies, suggests that risk of falling should be considered when selecting a hypnotic drug.