Pharmacology of insomnia: the enduring value of hypnotic benzodiazepine
Year: 2025
Type: article
Abstract: Insomnia is the most prevalent sleep disorder, affecting up to one-third of adults and associated with neuropsychiatric, metabolic, and cardiovascular morbidity. While cognitive behavioral therapy is the first-line treatment, pharmacological therapy remains essential for severe or persistent cases. Benzodiazepines and Z-drugs are the most widely used hypnotics, both acting as positive allosteric modulators of the GABA-A receptor. Although Z-drugs were promoted as selective and safer alternatives, evidence has challenged this view, showing reduced affinity to GABA-A receptors and adverse effects such as parasomnias (specifically for zolpidem), tolerance, and dependence. By contrast, short-intermediate acting benzodiazepines - particularly triazolam and lormetazepam - demonstrate broad efficacy across GABA-A receptor subtypes, supporting rapid induction of sleep, consolidation of restorative rest, and minimal residual impairment when appropriately timed. Triazolam provides rapid onset and is particularly effective for sleep-onset and middle-of-the-night insomnia, with equivalent efficacy to zolpidem but less next-day sedation than long-acting benzodiazepines. Furthermore, it is effective also in diminishing wake after sleep onset insomnia. Lormetazepam, with its short-to-intermediate half-life, combines high receptor affinity with favorable pharmacokinetics, ensuring sustained sleep without nocturnal awakenings and little or no next-morning psychomotor impairment. Lormetazepam also provides superior sleep maintenance and efficiency compared with zolpidem and zopiclone, with longer total sleep time and fewer nocturnal awakenings. Both compounds outperform Z-drugs for their much greater potency and breadth of receptor activation. When prescribed appropriately - at the lowest effective dose, for the shortest necessary duration, and with attention to patient chronotype, comorbidities, and lifestyle - hypnotic benzodiazepines remain safe and effective. Importantly, robust evidence refutes earlier claims of benzodiazepine-induced dementia, supporting their continued role as indispensable tools in the management of insomnia.
Source: Minerva Psychiatry
Author: Giovanni BIGGIO
Institutions: University of Cagliari, National Research Council
Language: English
Topic: Sleep and related disorders
Subfield: Experimental and Cognitive Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: hybrid
OpenAlex ID: W4416176346