Effect of chronic benzodiazepine and benzodiazepine receptor agonist use on sleep architecture and brain oscillations in older adults with chronic insomnia

Jun 26, 2025Sleep

Long-term use of benzodiazepines and similar drugs linked to changes in sleep patterns and brain rhythms in older adults with chronic insomnia

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Abstract

Chronic benzodiazepine and benzodiazepine receptor agonist use in older adults is associated with disrupted sleep architecture and altered brain oscillations.

Participants who chronically used benzodiazepines had lower N3 sleep duration and higher N1 sleep duration compared to good sleepers and individuals with insomnia.
Disrupted sleep architecture in chronic users was linked to altered brain activity patterns, specifically in the synchronization of sleep-related brain oscillations.
An exploratory analysis indicated that higher doses of benzodiazepines correlated with more significant disruptions in sleep micro-architecture and EEG spectrum.
These findings suggest that chronic use of these medications may be detrimental to sleep quality, potentially impacting cognitive function in older adults.

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STUDY OBJECTIVES: Insomnia in older adults is associated with widespread benzodiazepine (BZD) and benzodiazepine receptor agonist (BZRA) use despite evidence that chronic use disrupts sleep regulation and cognition. Little is known about BZD/BZRA effects on Non-rapid eye movement () slow oscillations (SO), spindles and their coupling, which is crucial for memory in older adults. Our objective was to investigate the effects of chronic BZD/BZRA use on sleep macro-architecture, electroencephalogram (EEG) relative power, SO and spindle characteristics and coupling.

METHODS: After habituation polysomnography, second-night data were analyzed from 101 participants (66.05 ± 5.84 years, range: 55-80 years, 73 per cent female) were categorized into three groups: good sleepers (GS, n = 28), individuals with insomnia (INS, n = 26) or individuals with insomnia who chronically use BZD/BZRA (MED, n = 47; diazepam equivalent: 6.1 ± 3.8 mg per use; >3 nights/week). We performed a comprehensive comparison of sleep architecture, EEG relative spectrum, and associated brain oscillatory activities, focusing on SO and spindles and their temporal coupling.

RESULTS: MED showed disrupted sleep architecture with lower N3 and higher N1 duration and spectral activity and altered sleep-related brain oscillations synchrony, compared to INS and GS. An exploratory interaction model suggested that chronic use of higher doses (mg per use) correlated with more pronounced disruptions in sleep micro-architecture and EEG spectrum.

CONCLUSIONS: Our results suggest that chronic BZD and BZRA use is associated with poorer sleep quality. Such alteration of sleep regulation-at the macro and micro-architectural levels-may contribute to the reported association between BZD/BZRA use and cognitive impairment in older adults. Statement of Significance Widespread use of sedative-hypnotics is driven by high insomnia rates among older adults. Chronic use can disrupt cognitive function; however, its impact on sleep regulation is not well understood. We assessed the effect of chronic benzodiazepine use in older adults using a between-group design involving good sleepers, drug-free individuals with insomnia disorder and individuals with insomnia disorder who chronically use sedative-hypnotics as a sleep aid. We performed a comprehensive comparison of sleep architecture, electroencephalogram relative spectrum, and associated NREM brain oscillations related to memory consolidation. We showed that chronic use of sedative-hypnotics is detrimental to sleep regulation-at the macro and micro-level-and this may contribute to the reported link between sedative-hypnotic use and cognitive impairment in older adults.

Key numbers

Participants with chronic insomnia using sedatives

Number of participants in the MED group using sedative-hypnotics.

12.8

decrease

Group effect on measured in the study.

N/A

Increased time in N1 sleep

MED group associated with more time in N1 sleep compared to GS and INS groups.

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Abstract

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