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Effects of hypnotic drugs on macroarchitecture of sleep


Insomnia has a high prevalence in adulthood and has great impact on social and cognitive performance. The pharmacological treatment might involve benzodiazepines, non-benzodiazepines hypnotics (Z-drugs), sedative antidepressants and other drugs; each of them may present different effects on sleep macroarchitecture. Long term use of benzodiazepines is associated with an increase of stage 1 non-REM sleep (N1), reduction of stage 3 non-REM sleep (N3) and REM sleep, and increase of sleep latency (SL) and REM sleep latency (REML). Z-drugs show little or no alterations on the macroarchitecture of sleep, and trazodone (a largely used sedative antidepressant) increases REM sleep compared to benzodiazepines.


The objective of this study was to compare the effect of different sleep-inducing drugs on the macroarchitecture of sleep.


The macroarchitecture of sleep (N1, N2, N3, REM, SL, SREM, and sleep efficiency - SE) was analyzed in 30159 polysomnographic reports (PSG), grouped according to the medication used or not by the patient in the night of the exam. Exclusion criteria were repeated PSG of the same patient, split-night or CPAP PSG reports, age below 18 years, apnea-hypopnea index > 5/hour and periodic limb movement index > 15/hour. The resulting sample had 7360 patients, aged 18 to 86, divided in no-drug (n=6893), benzodiazepines (n=209), z-drugs (n=77), trazodone (n=62), other drug (n=72) and multiple drugs (n=47) in order to run ANOVA with Games-Howell post-hoc tests.


Benzodiazepines showed, compared to no-drug, increase of SL (4 min), REML (32 min), and N2 (7 percentage points - pp), and reduction of N3 (5 pp) and REM sleep (2 pp). The use of trazodone resulted in significant increase of N3 compared to benzodiazepines (10 pp) and no-drug (5 pp), and was the only group that did not lowered REM sleep, compared to no-drug.


The results suggest that trazodone have a more benefic profile than benzodiazepines in preserving normal sleep macroarchitecture. These alterations caused by benzodiazepines might affect sleep functions, such as memory consolidation, restoration of individual performance, among others.


Insomnia, Benzodiazepines, Z-drugs, Trazodone, Sleep macroarchitecture


Área Clínica


Instituto Paranaense de Otorrinolaringologia - Parana - Brasil, Universidade Federal do Paraná - Parana - Brasil


Bárbara Kawano Raposo, Fernando Mazzilli Louzada, João Guilherme Fiorani Borgio