Association between psychotropic medication and sleep microstructure: evidence from large population studies

Study objectives: To assess the association between psychotropic medications and sleep microstructure in large community-based cohorts of older people. Methods: We analyzed overnight polysomnograms of 381 women from the Study of Osteoporotic Fractures (SOF) and 2,657 men from the Osteoporotic Fractures in Men Sleep Study (MrOS), who either used no psychotropic medication (n=2,819), only benzodiazepines (n=112), or only selective serotonin reuptake inhibitors (SSRI) (n=107). Sleep microstructure (cyclic alternating pattern, CAP) was compared between the no medication group and psychotropic medication groups using the Mann-Whitney U-test. Significant differences were investigated using multivariable linear regression adjusted for confounders. Results: CAP rate, arousal index, apnea-hypopnea index, and the frequency of slow, low-amplitude electroencephalography activation phases were significantly lower in MrOS participants using benzodiazepines than participants not taking psychotropic medication. SSRI users in MrOS experienced no altered sleep microstructure compared to those with no psychotropic use. SOF participants using benzodiazepines did not show similar associations with sleep microstructure. However, SSRI users from SOF had a significantly higher frequency of rapid, high-amplitude electroencephalography activation phases (A2 + 3) and periodic limb-movement index than participants not taking psychotropic medication. Multivariable linear regression adjusted for demographic, lifestyle, mood disorders, and health variables indicated additional significant associations between CAP rate and A2 + 3 index, respectively, and benzodiazepine usage in older men, and between CAP rate and SSRI usage in older women. Conclusions: We identified significant associations between sleep microstructure and psychotropic drugs in MrOS and SOF highlighting the importance of comprehensive sleep analysis, including CAP. Our results may help to better understand the differences in sleep-wake mechanisms based on psychotropic usage. Clinical trial registration: Registry: ClinicalTrials.gov; Title: Outcomes of Sleep Disorders in Older Men; Identifier: NCT00070681; URL: https://clinicaltrials.gov/ct2/show/record/NCT00070681.