The Z-drugs
zolpidem,
zopiclone, and
zaleplon were hailed as the innovative
hypnotics of the new millennium, an improvement to traditional
benzodiazepines in the management of
insomnia. Increasing reports of adverse events including bizarre behavior and falls in the elderly have prompted calls for caution and regulation. Z-drugs have significant
hypnotic effects by reducing sleep latency and improving sleep quality, though duration of sleep may not be significantly increased. Z-drugs exert their effects through increased γ-
aminobutyric acid (
GABA) transmission at the same
GABA-type A receptor as
benzodiazepines. Their pharmacokinetics approach those of the ideal
hypnotic with rapid onset within 30 min and short half-life (1-7 h).
Zopiclone with the longest duration of action has the greatest residual effect, similar to short-acting
benzodiazepines. Neuropsychiatric adverse events have been reported with
zolpidem including
hallucinations,
amnesia, and
parasomnia.
Poisoning with Z-drugs involves predominantly sedation and
coma with supportive management being adequate in the majority.
Flumazenil has been reported to reverse sedation from all three Z-drugs. Deaths from Z-drugs are rare and more likely to occur with polydrug overdose. Z-drugs can be detected in blood, urine, oral fluid, and postmortem specimens, predominantly with liquid chromatography-mass spectrometry techniques.
Zolpidem and
zaleplon exhibit significant postmortem redistribution.
Zaleplon with its ultra-short half-life has been detected in few clinical or forensic cases possibly due to assay unavailability, low frequency of use, and short window of detection. Though Z-drugs have improved pharmacokinetic profiles, their adverse effects, neuropsychiatric sequelae, and incidence of
poisoning and death may prove to be similar to older
hypnotics.