Possible Interaction: Caffeine and Zolpidem

“As zolpidem, a short-acting hypnotic, is an atypical GABAA-BZD agonist, we investigated when caffeine would counteract the effects of zolpidem as well.”

“It is proposed that by modifying the cellular redox state, caffeine ultimately reduces the pool of reactive oxygen species, thereby increasing the bioavailability of endogenous melatonin for interaction with zolpidem.”

“Paradoxically, in some cases caffeine appears to slightly enhance zolpidem sedation.”

“ Zolpidem attenuated the caffeine-induced decrease in SE and increased spindle density in the caffeine plus zolpidem combination compared with placebo.”

“ Caffeine coadministration modestly increased maximum plasma concentration (Cmax) and area under the plasma concentration‐time curve of zolpidem by 30–40%, whereas zolpidem did not significantly affect the pharmacokinetics of caffeine or its metabolites.”

“ Caffeine partially , but not completely, reversed most pharmacodynamic effects of zolpidem.”

“Thus, caffeine only incompletely reverses zolpidem's sedative and performance‐impairing effects, and cannot be considered as an antidote to benzodiazepine agonists.”

“In combination, zolpidem attenuated caffeine ’s effects on WAKE, whilst trazodone attenuated its effects on NREM sleep, NREM bout duration, delta activity, body temperature and locomotor activity.”