The evolution of hypnotics

Abstract

Insomnia is one of the most prevalent medico-social problems, leading to a significant decline in quality of life, reduced work productivity, and an increased risk of somatic and psychiatric diseases.
Pharmacotherapy remains an important treatment modality, yet the history of hypnotic drugs is a continuous search for a balance between efficacy and safety.
The aim of study – to provide a comprehensive analysis of the evolution of hypnotic agents, systematize them by generation, mechanism of action, clinical advantages, and disadvantages, as well as to identify key trends and future perspectives for this pharmacological group. An analysis and systematization of scientific literature, clinical guidelines, and key studies covering the
history, pharmacology, and clinical application of sleeping medications were performed. The first generations of hypnotics (chloral hydrate, barbiturates), characterized by high efficacy but a
low safety profile and significant dependence potential, are reviewed. The benzodiazepine revolution of the 1960s is analyzed, which offered a much higher therapeutic index but did not solve the problems of long term dependence and sleep architecture disruption. The emergence of non-benzodiazepine "Z-drugs" is highlighted as an attempt to achieve greater selectivity for the α1
subunit of the GABA-A receptor. Special attention is paid to the modern era, which marks a paradigm shift from GABAergic sedation to physiological sleep modulation through fundamentally new mechanisms: agonism at melatonin receptors (the chronobiotic approach) and antagonism at orexin receptors (the "anti-arousal" approach). The practice of
off-label use of drugs from other groups (antihistamines, antidepressants, antipsychotics, gabapentinoids) is also analyzed.
Thus, the evolution of hypnotic drugs demonstrates a clear trend towards increased specificity and safety, reflecting a deeper understanding of sleep neurobiology. Modern pharmacotherapy aims for a
targeted influence on the natural regulatory mechanisms of the sleep-wake cycle with minimal risk of dependence and side effects. It is emphasized that pharmacotherapy is a component of comprehensive care, where cognitive-behavioral therapy for insomnia (CBT-I) is the gold standard for treating chronic insomnia.