Regular Research Article|Articles in Press

Interactions of Insomnia and Sedative-Hypnotic Drug Use Associated with Frailty Over Time Among Older Adults

Published:February 07, 2023DOI:


      • What is the primary question addressed by this study?
      • Sedative-hypnotic drugs are widely used to treat insomnia; however, the effect of sedative-hypnotic drugs on frailty remained unclear.
      • What is the main finding of this study?
      • Using a nationwide survey, we found that both insomnia and medication use were significantly and independently associated with an increased frailty risk.
      • What is the meaning of the finding?
      • Given the potential frailty risk of sedative-hypnotic drug, nonpharmacological treatment might should be firstly considered for treating insomnia.



      Insomnia and frailty are prevalent in older adults. This study aimed to elucidate the impact of insomnia and sedative-hypnotic use on the frailty rate over time.


      We used data from community-dwelling older adults (mean ± SD age = 69.4 ± 8.2 years) from the Healthy Aging Longitudinal Study in Taiwan (HALST). A total of 4,744 participants were included in the study and were followed up for an average of 3.2 years. Frailty was assessed using the Fried criteria. Self-reported sleep problems, sedative-hypnotic use, and claims records from the National Health Insurance database were used. The generalized equation estimation (GEE) approach was applied to account for correlations between repeated measures. The average impact of insomnia and drug use on frailty over time was estimated by adjusting for potential confounding factors using the logic link in the GEE approach.


      The adjusted odds ratio (OR) of frailty was 1.41 (95% CI: [1.16, 1.72], Z-test statistics Z = 3.39, p <0.001) for insomnia and 1.52 ([1.16, 2.00], Z = 3.00, p = 0.0027) for sedative-hypnotic use. Interactions between insomnia and sedative-hypnotic use with frailty were not statistically significant. Long sleep duration > 8 hours, daytime sleepiness, and sleep apnea was also associated with an increased likelihood of developing frailty. Notably, a dose-response relationship between sedative-hypnotic drug use and frailty was observed.


      Insomnia and sedative-hypnotic use were independently associated with increased frailty. The implementation of nonpharmacological treatments to attenuate insomnia may reduce frailty rates.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to The American Journal of Geriatric Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Crowley K
        Sleep and sleep disorders in older adults.
        Neuropsychol Rev. 2011; 21: 41-53
        • Ohayon MM
        • Carskadon MA
        • Guilleminault C
        • et al.
        Meta-analysis of quantitative sleep parameters from childhood to old age in healthy individuals: developing normative sleep values across the human lifespan.
        Sleep. 2004; 27: 1255-1273
        • Kwok CS
        • Kontopantelis E
        • Kuligowski G
        • et al.
        Self-reported sleep duration and quality and cardiovascular disease and mortality: a dose-response meta-analysis.
        J Am Heart Assoc. 2018; 7e008552
        • Thomas SJ
        • Sakhuja S
        • Colantonio LD
        • et al.
        Insomnia diagnosis, prescribed hypnotic medication use, and risk for serious fall injuries in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study.
        Sleep. 2022; 45: zsac063
        • Clegg A
        • Young J
        • Iliffe S
        • et al.
        Frailty in elderly people.
        Lancet. 2013; 381: 752-762
        • Collard RM
        • Boter H
        • Schoevers RA
        • et al.
        Prevalence of frailty in community-dwelling older persons: a systematic review.
        J Am Geriatr Soc. 2012; 60: 1487-1492
        • Wai JLT
        • Yu DSF
        The relationship between sleep–wake disturbances and frailty among older adults: a systematic review.
        J Adv Nurs. 2020; 76: 96-108
        • Pourmotabbed A
        • Boozari B
        • Babaei A
        • et al.
        Sleep and frailty risk: a systematic review and meta-analysis.
        Sleep Breath. 2020; 24: 1187-1197
        • Ensrud KE
        • Blackwell TL
        • Ancoli-Israel S
        • et al.
        Sleep disturbances and risk of frailty and mortality in older men.
        Sleep Med. 2012; 13: 1217-1225
        • Moreno-Tamayo K
        • Manrique-Espinoza B
        • Morales-Carmona E
        • et al.
        Sleep duration and incident frailty: the Rural Frailty Study.
        BMC Geriatr. 2021; 21: 1-7
        • Nemoto Y
        • Sato S
        • Kitabatake Y
        • et al.
        Bidirectional relationship between insomnia and frailty in older adults: a 2-year longitudinal study.
        Arch Gerontol Geriatr. 2021; 97104519
        • Holbrook AM
        • Crowther R
        • Lotter A
        • et al.
        Meta-analysis of benzodiazepine use in the treatment of insomnia.
        Cmaj. 2000; 162: 225-233
        • Riemann D
        • Perlis ML
        The treatments of chronic insomnia: a review of benzodiazepine receptor agonists and psychological and behavioral therapies.
        Sleep Med Rev. 2009; 13: 205-214
        • Díaz-Gutiérrez MJ
        • Martínez-Cengotitabengoa M
        • de Adana ES
        • et al.
        Relationship between the use of benzodiazepines and falls in older adults: a systematic review.
        Maturitas. 2017; 101: 17-22
        • Charlson F
        • Degenhardt L
        • McLaren J
        • et al.
        A systematic review of research examining benzodiazepine-related mortality.
        Pharmacoepidemiol Drug Saf. 2009; 18: 93-103
        • Chen C-Y
        • Wu S-C
        • Chen L-J
        • et al.
        The prevalence of subjective frailty and factors associated with frailty in Taiwan.
        Arch Gerontol Geriatr. 2010; 50: S43-S47
        • Peklar J
        • O'Halloran AM
        • Maidment ID
        • et al.
        Sedative load and frailty among community-dwelling population aged≥ 65 years.
        J Am Med Dir Assoc. 2015; 16: 282-289
        • Cil G
        • Park J
        • Bergen AW
        Self-reported prescription drug use for pain and for sleep and incident frailty.
        J Am Geriatr Soc. 2019; 67: 2474-2481
        • Hsu C-C
        • Chang H-Y
        • Wu I-C
        • et al.
        Cohort profile: the healthy aging longitudinal study in Taiwan (HALST).
        Int J Epidemiol. 2017; 46 (1106-1106j)
        • Wu C-S
        • Lai M-S
        • Gau SS-F
        • et al.
        Concordance between patient self-reports and claims data on clinical diagnoses, medication use, and health system utilization in Taiwan.
        PloS One. 2014; 9e112257
        • Wu C-S
        • Kuo C-J
        • Su C-H
        • et al.
        Using text mining to extract depressive symptoms and to validate the diagnosis of major depressive disorder from electronic health records.
        J Affect Disord. 2020; 260: 617-623
        • Fried LP
        • Tangen CM
        • Walston J
        • et al.
        Frailty in older adults: evidence for a phenotype.
        J Gerontol A Biol Sci Med Sci. 2001; 56: M146-M157
        • Chang C-C
        • Wu C-S
        • Tseng H-Y
        • et al.
        Assessment of incident frailty hazard associated with depressive symptoms in a Taiwanese longitudinal study.
        Int Psychogeriatr. 2022; 34: 61-70
        • Kojima G
        • Taniguchi Y
        • Iliffe S
        • et al.
        Transitions between frailty states among community-dwelling older people: a systematic review and meta-analysis.
        Ageing Res Rev. 2019; 50: 81-88
        • Kawata Y
        • Maeda M
        • Sato T
        • et al.
        Association between marital status and insomnia-related symptoms: findings from a population-based survey in Japan.
        EurJ Public Health. 2020; 30: 144-149
        • Jeon GS
        • Jang SN
        • Park S
        Social support, social network, and frailty in Korean elderly.
        J Korean Geriatr Soc. 2012; 16: 84-94
        • Kent de Grey RG
        • Uchino BN
        • Trettevik R
        • et al.
        Social support and sleep: a meta-analysis.
        Health Psychol. 2018; 37: 787
        • Coelho T
        • Paúl C
        • Gobbens RJ
        • et al.
        Determinants of frailty: the added value of assessing medication.
        Front Aging Neurosci. 2015; 7: 56
        • Sinha SS
        Trauma-induced insomnia: a novel model for trauma and sleep research.
        Sleep Med Rev. 2016; 25: 74-83
        • Liang K-Y
        • Zeger SL
        Longitudinal data analysis using generalized linear models.
        Biometrika. 1986; 73: 13-22
        • Cheung DSK
        • Kwan RYC
        • Wong ASW
        • et al.
        Factors associated with improving or worsening the state of frailty: a secondary data analysis of a 5-year longitudinal study.
        J Nurs Scholarsh. 2020; 52: 515-526
        • Pourmotabbed A
        • Boozari B
        • Babaei A
        • et al.
        Sleep and frailty risk: a systematic review and meta-analysis.
        Sleep Breath. 2020; 24: 1187-1197
        • Irwin MR
        • Olmstead R
        • Carroll JE
        Sleep disturbance, sleep duration, and inflammation: a systematic review and meta-analysis of cohort studies and experimental sleep deprivation.
        Biol Psychiatry. 2016; 80: 40-52
        • Bano G
        • Trevisan C
        • Carraro S
        • et al.
        Inflammation and sarcopenia: a systematic review and meta-analysis.
        Maturitas. 2017; 96: 10-15
        • Pan W
        • Kastin AJ
        Leptin: a biomarker for sleep disorders?.
        Sleep Med Rev. 2014; 18: 283-290
        • Lana A
        • Valdés-Bécares A
        • Buño A
        • et al.
        Serum leptin concentration is associated with incident frailty in older adults.
        Aging Dis. 2017; 8: 240
        • Bohannon RW
        Population representative gait speed and its determinants.
        J Geriatr Phys Ther. 2008; 31: 49-52
        • Pourmotabbed A
        • Ghaedi E
        • Babaei A
        • et al.
        Sleep duration and sarcopenia risk: a systematic review and dose-response meta-analysis.
        Sleep Breath. 2020; 24: 1267-1278
        • Simpson NS
        • Banks S
        • Arroyo S
        • et al.
        Effects of sleep restriction on adiponectin levels in healthy men and women.
        Physiol Behav. 2010; 101: 693-698
        • Komici K
        • Dello Iacono A
        • De Luca A
        • et al.
        Adiponectin and sarcopenia: a systematic review with meta-analysis.
        Front Endocrinol. 2021; 12: 329
        • Baniak LM
        • Yang K
        • Choi J
        • et al.
        Long sleep duration is associated with increased frailty risk in older community-dwelling adults.
        J Aging Health. 2020; 32: 42-51
        • Tomita S
        • Matsuura N
        • Ichinohe T
        The combined effects of midazolam and propofol sedation on muscle power.
        Anaesthesia. 2013; 68: 478-483
        • Kronholm E
        • Sallinen M
        • Era P
        • et al.
        Psychomotor slowness is associated with self-reported sleep duration among the general population.
        J Sleep Res. 2011; 20: 288-297
        • Rios P
        • Cardoso R
        • Morra D
        • et al.
        Comparative effectiveness and safety of pharmacological and non-pharmacological interventions for insomnia: an overview of reviews.
        Syst Rev. 2019; 8: 1-16
        • Soong C
        • Burry L
        • Greco M
        • et al.
        Advise non-pharmacological therapy as first line treatment for chronic insomnia.
        BMJ. 2021; 372n680