Psychotropic medicines are known to impair cognitive function acutely, but the specific effects of individual substances remain underexplored. This study investigates the effects of dexamphetamine and zolpidem on cognitive performance to quantify the potential risk of intake and their pharmacokinetic and pharmacodynamic relationship. This randomized, double-blind, placebo-controlled trial (EudraCT 2021-005381 - 17) included 60 healthy men aged 26 ± 5 (mean ± SD) years. Participants received a single oral dose of 30-mg dexamphetamine, 5-mg zolpidem, or placebo (n = 20 per group). Cognitive performance was assessed at baseline and 3 and 8 h after dosing using the computerized Psytest system. Dexamphetamine and zolpidem improved sustained attention, with significant reduction of omissions at 8 h. Reaction time improved in both groups, but zolpidem impaired phasic alertness. Working memory remained unchanged. Plasma concentration of dexamphetamine and zolpidem was 70.8 ± 10.4 ng/mL and 39.0 ± 20.7 ng/mL at 3 h and 45.9 ± 7.9 ng/mL and 8.7 ± 6.6 ng/mL at 8 h, respectively. No correlation between drug plasma concentration and cognitive performance measures was demonstrable. Dexamphetamine caused the strongest subjective effects and highest liking ratings, whereas zolpidem elicited greater subjective dislike. Tolerability was best with placebo, followed by zolpidem and dexamphetamine. Single therapeutic doses of dexamphetamine and zolpidem modestly affected cognitive function 3 h after intake, with no relationship between cognitive performance and the study medicines' plasma concentration. Both medicines improve cognition after 8 h but differed in subjective emotional effects. Nevertheless, generalizability is limited by the inclusion of healthy men only. Trial Registration: EudraCT: Nr: 2021-005381-17.

How sleep medications affect brain physiology over time remains largely unknown. Prior pharmacodynamic work has established distinct spectral signatures of GABA-A receptor modulators vs. DORAs in younger or mixed adult samples. Here, we report how sleep EEG effects evolve from acute (days 1-2) to chronic (days 29-30) exposure in older adults with insomnia meeting DSM-5 criteria, and how within-person changes relate to Insomnia Severity Index (ISI). This analysis used data from a randomized, double-blind, placebo-controlled, active-comparator phase III trial (May 2016-January 2018). A subset of 249 participants was analyzed for EEG outcomes. Participants received 5 mg or 10 mg LEM (LEM5, LEM10), 6.25 mg extended-release zolpidem (ZOL), or placebo nightly for 30 days. Polysomnography was collected at baseline, after acute exposure, and after chronic exposure. Acute ZOL exposure produced significant increases in non-rapid eye movement (NREM) slow oscillation (SO), sigma, beta, and gamma power, with decreases in delta and theta compared to all treatment groups. These effects persisted with chronic exposure, alongside an alpha increase from acute to chronic exposure. LEM10 showed minimal acute effects but, with continued use, increased SO and decreased alpha power. The degree of SO power increase from acute to chronic exposure predicted improvements in ISI scores, driven by the LEM10 group. ZOL showed similar REM effects, whereas LEM5, but not LEM10, reduced REM sigma and beta power. These findings demonstrate that ZOL and LEM differentially modulate sleep EEG, with sustained SO enhancement under LEM10 linked to symptom improvement.

Insomnia is the most prevalent sleep disorder in adults, representing a major public health problem. Healthcare management in a specific area first requires analysing its current practices and issues. We conducted a retrospective observational study of over 100,000 patients from two large primary care databases in the public healthcare Department of Sagunto (Valencia, Spain), from 2009 to 2017. Cases of insomnia were defined by ICD-10 codes, and prescriptions of hypnotics were collected. The data analysis was performed on epidemiological aspects, comorbidity, diagnosis and treatment of insomnia. A significant increase in the incidence of insomnia occurred, rising from 58.9 per 1000 inhabitants (95% CI: 57.7-60.0) in 2009 to 91.4 per 1000 inhabitants (95% CI: 90.0-92.9) in 2017. A total of 12,404 prescriptions for hypnotics and sedatives were issued, including 39.8% for indications other than insomnia. Lorazepam was the most frequently prescribed hypnotic-sedative (36%), followed by zolpidem (21.1%); 54% of insomnia cases revealed more prescription units than medical consultations, suggesting automatic renewals. Excessive prescription of hypnotic drugs for insomnia, along with a lack of follow-up, were identified as significant issues.

The gamma-aminobutyric acid type A (GABAA) receptor is the primary mediator of inhibitory neurotransmission in the central nervous system and represents an important pharmacological target for sedative and anesthetic agents. However, many conventional anesthetics are associated with adverse effects and pharmacokinetic limitations, highlighting the need for safer compounds with improved delivery to the central nervous system and better therapeutic profiles. In this study, natural compounds were evaluated as potential modulators of the GABAA receptor using an integrated computational approach. Molecular docking was performed using AutoDock Vina, followed by pharmacokinetic and drug-likeness evaluation using SwissADME and molecular dynamics simulations to examine binding stability. Several phytochemicals exhibited docking scores comparable to the sedative drug zolpidem (-7.1 to -7.6 kcal/mol). However, pharmacokinetic predictions indicated that most natural compounds had limited ability to cross the blood-brain barrier despite favorable gastrointestinal absorption. Zolpidem was therefore used as a reference compound capable of penetrating the central nervous system to evaluate the pharmacokinetic requirements necessary for effective receptor targeting. Molecular dynamics simulations demonstrated stable receptor-ligand interactions and structural stability of the complex throughout the trajectory. These findings highlight the importance of integrating binding affinity with pharmacokinetic feasibility when prioritizing candidate modulators of the GABAA receptor. Although several natural compounds showed promising interaction profiles, further structural optimization and experimental validation are required.

Parricide refers to the act of murdering one's father, mother, or a close relative without involving harm to children. Juvenile parricide represents a rare form of criminal behavior that, despite its infrequency, receives considerable media attention and provokes substantial public concern. Due to its exceptionally low base rate, forecasting its occurrence remains challenging, if not unattainable. We report a case of a 45-year-old man who was murdered by his juvenile daughter after he disapproved of her relationship with her boyfriend, as she held a grudge and acted in revenge, using a sharp weapon and burning the body to hinder identification and conceal the crime. The scene of the incident showed accelerant residues and blood stains, and the body was recovered in a pugilistic attitude from the restroom. The postmortem examination revealed multiple chop and stab wounds on the head, face, and extremities. No soot particles were present in the airways, and histopathology also confirmed the absence of antemortem burns. Carboxyhemoglobin was negative, ruling out death from burns. Toxicological analysis detected alcohol and zolpidem in the blood and visceral organs. DNA profiling confirmed identity, and the cause of death was attributed to hemorrhagic shock due to sharp force injuries, and the manner of death was homicide. This case illustrates the combination of sedation, sharp-force assault, and postmortem burning, highlighting the complexities of juvenile female patricide and familial homicides. It emphasizes the crucial role of integrated forensic pathology and toxicology in reconstructing events, uncovering causes and dynamics, and guiding investigative approaches through autopsy findings and forensic evidence, while outlining medicolegal practices to aid experts in the pursuit of justice.

Chronic insomnia is a common condition that significantly burdens patients and increases the risk of various comorbidities. Cognitive Behavioral Therapy for Insomnia (CBT-I) is the recommended first-line treatment and has shown strong, long-lasting effects with fewer side effects compared to medication. This article presents a representative case study of a woman with long-term insomnia,illustrating the core components and practical implementation of CBT-I, including the combination with medication tapering. CBT-I targets the maintaining factors of insomnia through behavioral techniques (e.g. sleep restriction) and cognitive interventions, and restoring daytime balance. Up to 80% of patients experience clinically relevant improvements, even with comorbid conditions. In contrast, sleep medications like temazepam or zolpidem should be used cautiously, for no longer than 2-4 weeks. CBT-I leads to more sustainable outcomes and supports patient autonomy. Wider implementation in clinical practice is hindered by limited awareness, access, and reimbursement, despite strong evidence for its effectiveness.

Drug-facilitated sexual assault (DFSA) may involve a diverse array of substances, including illicit drugs, prescription medications, and over-the-counter pharmaceuticals. Hair analysis has emerged as a valuable forensic tool, offering an extended window of detection spanning several months. However, interpreting drug concentrations in hair can be challenging in forensic cases, as there are still substantial disparities in drug concentration findings across studies, or even no data available in the literature. This compendium seeks to contribute to the understanding and interpretation of forensic cases involving hair analysis. This study included hair analysis results upon prosecutor request over 6 years in Grenoble Forensic Laboratory from 2019 to 2024. Segmental hair analysis was performed using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) on Sciex® 5500QT and Waters® TQ-XS mass spectrometers, following Society of Hair Testing guidelines. Screened substances included drugs of abuse, benzodiazepines, sedative medications, and gamma-hydroxybutyrate (GHB), depending on the case, following French Society of Analytical Toxicology guidelines. Hair proficiency quality testing ensured reproducible results. In this compendium, 22 authentic DFSA cases are described with hair analysis. The cohort predominantly involved female victims (95%) aged 13-47 years. Hair analysis was positive in nine cases (41%), revealing the presence of at least one psychoactive substance. Substances identified were alimemazine, alprazolam, bromazepam, cetirizine, clozapine, codeine, cyamemazine, hydroxyzine, oxazepam, zolpidem, and 3,4-methylenedioxymethamphetamine (MDMA). The chemical profile observed primarily included sedating and amnesic pharmaceuticals, but not only. This compendium adds valuable data in the literature for better hair drug concentration interpretation in forensic cases.

Little information is available on the use of zaleplon during breastfeeding. Some expert opinion considers zaleplon to be not recommended during breastfeeding.[1,2] Because of the low levels of zolpidem in breastmilk and its short half-life, amounts ingested by the infant are small and would not be expected to cause any adverse effects in older breastfed infants. Monitor infants for excess sedation, hypotonia, and respiratory depression.

Chronic insomnia affects 10% of adults, with hypnotic medications widely prescribed. Residual pharmacological effects upon awakening may affect postural stability, increasing fall risk. We used a Network Meta-Analysis (NMA) framework to compare the influence of hypnotic medications on posture upon awakening. A systematic review and frequentist random-effects NMA was conducted following the PRISMA guidelines and a pre-determined protocol. We searched PubMed, EMBASE, ClinicalTrials.gov, WHO-ICTRP for randomized controlled trials until 10/21/2025, documenting the effects of hypnotics on static (body sway) and dynamic (walking test) balance. Risk-of-bias and confidence in evidence were assessed with RoB2 and CINeMA. Of 4459 identified records, 23 studies were included in the review. Most in-label doses of hypnotics showed no significant impact on postural stability in the morning compared to placebo, except zopiclone 7.5 mg both at bedtime (Standardized Mean Difference-SMD = 0.22, 95% C.I.[0.22;0.1.24]) and middle-of-the-night awakening (SMD = 4.45, 95% C.I.[3.54;5.36]), while zolpidem 6.5 mg extended-release proved worse in the subset including older adults (SMD = 0.39, 95% C.I.[0.01;0.76]). Same applied to middle-of-the-night evaluations for zopiclone 7.5 mg (SMD = 0.98, 95% C.I.[0.07;1.90]), zolpidem 6.5 mg extended-release (SMD = 1.14, 95% C.I.[0.30;1.98]), and zolpidem 10 mg (SMD = 1.60, 95% C.I.[0.63;2.58]). Confidence in the evidence was mainly low/very-low. Most regulatory-approved hypnotics did not significantly impair postural balance at in-label doses. However, caution is warranted for longer-acting and high-doses, particularly in high fall-risk individuals, including older adults. Given the age-related decline in postural reflexes and heightened sensitivity to CNS depressants, lower doses and shorter half-life drugs should be preferred whenever hypnotic therapy is necessary. Future research is needed to explore dynamic balance further to optimize prescribing guidelines for fall prevention in vulnerable populations.