Zolpidem is a non-benzodiazepine agent used for short-term treatment of insomnia. Several cases of dependence and withdrawal from zolpidem are reported in the literature. Furthermore, involuntary movements after prolonged zolpidem misuse have been described. In this case report, a 69-year-old Italian woman with no history of diagnosed psychiatric or neurologic diseases developed uncontrolled movements and a depressive-anxious syndrome after twelve-year zolpidem misuse. The underlying mechanisms of involuntary movements occurring after long-term zolpidem intake are unknown; yet, we suggest that zolpidem might induce an increase in dopamine release through inhibition of gamma-aminobutyric acid neurons tonically suppressing dopamine cells. Future studies on the occurrence of persistent disorders after long-term benzodiazepine or Z-drug abuse are needed and clinicians should pay attention to the risk of tardive syndromes related to zolpidem misuse, especially in the case of long-term intake of over-therapeutic dosages.

In the decade since its debut, the Mesocircuit Hypothesis (MH) has provided researchers a scaffolding for interpreting their findings by associating subcortical-cortical dysfunction with the loss and recovery of consciousness following severe brain injury. Here, we leverage new findings from human and rodent lesions, as well as chemo/optogenetic, tractography, and stimulation studies to propose the external segment of the globus pallidus (GPe) as an additional node in the MH, in hopes of increasing its explanatory power. Specifically, we discuss the anatomical and molecular mechanisms involving the GPe in sleep-wake control and propose a plausible mechanistic model explaining how the GPe can modulate cortical activity through its direct connections with the prefrontal cortex and thalamic reticular nucleus to initiate and maintain sleep. The inclusion of the GPe in the arousal circuitry has implications for understanding a range of phenomena, such as the effects of the adenosine (A2A) and dopamine (D2) receptors on sleep-wake cycles, the paradoxical effects of zolpidem in disorders of consciousness, and sleep disturbances in conditions such as Parkinson's Disease.

Objective: Evaluate the data on the psychotropic drugs dispensed by private community pharmacies before and during the SARS-CoV-2 pandemic. Methods: This cross-sectional study compared the quarterly and annual consumption of psychotropic drugs per Defined Daily Dose per 1000 inhabitants-day (DHD). Interrupted time series were also constructed to expose changes in the consumption pattern in the periods before and after March 2020. Results: Among the 20 most consumed psychoactive drugs, 12 were antidepressants, for example, escitalopram (DHD 7.996 and 10.626; p < 0.001), and sertraline (DHD 6.321 and 8.484; p < 0.001), in addition to the hypnotic zolpidem (DHD 6.202 and 8.526; p < 0.001). The time series reveals (R 2 value) a variation in drug dispensing, in DHD values, during the pandemic. Conclusion: Despite the higher variance, a significant increase is clearly seen in the consumption trends of psychoactive drugs, particularly antidepressants, consistent with the pandemic's influence on the general population's mental health.

The aim of the present study was to analyze the association between the prescription of Silexan and the recurrence of general practitioner (GP) repeat consultations because of disturbed sleep versus benzodiazepine receptor agonists including zolpidem, zopiclone, and zaleplon (Z-drugs). This retrospective cohort study was based on data from the IQVIA Disease Analyzer (DA) database. The study included adult patients treated by 1284 GPs in Germany with a documented sleep disorder and their first prescription of Silexan or Z-drug (prescription between January 2010 and October 2020). The recurrence of seeking medical advice because of sleep disorders in the 15-365 days after the first prescription was evaluated. Multivariate regression models were used, adjusted for age, sex, insurance status, and defined co-diagnoses. Data were available for 95,320 (Silexan: 5204; Z-Drug: 90,526) patients. In total, 15.6% of the Silexan patients and 28.6% of the Z-drug patients had a further documented GP consultation because of a sleep disorder. Silexan prescription was associated with significantly lower odds of recurrent sleep disorder diagnosis in the 15-365 days after the index date (Odds Ratio (OR): 0.56; 95% confidence intervals (CI): 0.51-0.60), although mental burden levels appeared higher in this group. Our study shows that the prescription of Silexan to adult patients consulting GPs for disturbed sleep results in less frequent repeat consultations than Z-drugs. This may support Silexan's role as an efficacious, self-enabling, well-tolerated, and sustained treatment option. Because Silexan is a proven anxiolytic, its impact in improving undiagnosed anxiety disorders may have had a lasting effect for certain patients.

We describe the case of a 17-year-old woman diagnosed with complex regional pain syndrome (CRPS) at a pain clinic after the second dose of the COVID-19 vaccine. She was referred to our department for surgical treatment of movement disorder seven months after the second inoculation. Baclofen (50 µg), administered intrathecally, improved the involuntary movements of her right hand. After administration of zolpidem (5 mg), involuntary movements of the right index finger almost disappeared. However, neither zolpidem nor intrathecal baclofen improved the limited range of motion of the first joint of the left-hand finger. Despite various reports on CRPS development after vaccination, only one case post COVID-19 vaccination has been reported. Therefore, healthcare providers should keep in mind that CRPS can appear after the COVID-19 vaccination.

Benzodiazepines and z-hypnotics are detected in the majority of fatal overdose cases in Norway, often in combination with other drugs of abuse, and their concentrations in peripheral blood might be important to elucidate the cause of death. In some forensic autopsies, peripheral blood is however not available. The aim of the present study was to compare concentrations of benzodiazepines and z-hypnotics in five alternative matrices to assess whether these concentrations are comparable to concentrations in peripheral blood. A total of 109 forensic autopsy cases were included. Peripheral blood, cardiac blood, pericardial fluid, psoas muscle, lateral vastus muscle and vitreous humour from each case were analysed using UHPLC-MS/MS. We were able to detect clonazepam, 7-aminoclonazepam, flunitrazepam, 7-aminoflunitrazepam, nitrazepam, 7-aminonitrazepam, diazepam, nordiazepam, oxazepam, alprazolam, midazolam, zopiclone and zolpidem in all the analysed matrices. Concentrations measured in vitreous humour were generally much lower than those of peripheral blood for all compounds except zopiclone. 7-amino metabolite concentrations were high compared to the parent compounds, although less so for the muscle samples. In muscles, concentrations of the parent nitrobenzodiazepines were higher than in peripheral blood, but for the other compounds, concentrations in muscle showed good correspondence with peripheral blood. Both cardiac blood and pericardial fluid were viable alternative matrices for peripheral blood, although a larger variation and a tendency for higher concentrations in pericardial fluid was observed. This study shows that cardiac blood, psoas and lateral vastus muscle samples and pericardial fluid can give comparable concentrations to peripheral blood for benzodiazepines and z-hypnotics, while vitreous humour was less suitable. The concentrations in alternative matrices must, however, be interpreted carefully.

In 2019, a pandemic caused by the SARS-CoV-2 virus began. The fight against COVID-19 required the introduction of a number of restrictive measures, in particular the introduction of quarantine for the population and isolation of the sick, which, along with the direct effect of the virus on the nervous system, led to a significant spread of sleep disorders. In this regard, questions have become relevant about the choice of drugs for the correction of sleep disorders, about which sleeping pills will be safe in conditions of acute illness and during the recovery period after COVID-19. The article discusses the prevalence and therapy of insomnia in patients with acute COVID-19 and in patients with postcovid syndrome. The pharmacological effects and safety of zolpidem, a non-benzodiazepine short-acting hypnotic drug belonging to the class of imidazopyridines, which is used in short courses for both acute and transient insomnia and chronic insomnia, are described. The data on the ability of zolpidem to improve memory after a night's sleep are given. The possibility of its use in acute COVID-19 and postcovid syndrome is being evaluated.

This report describes polysomnography and sleep diary exposure-response analyses from Study E2006-G000-304 (Study 304), a 1-month trial of 5- or 10-mg lemborexant, zolpidem, or placebo; and Study E2006-G000-303 (Study 303), a 6-month trial of 5- or 10-mg lemborexant or placebo. Studies 304 and 303 included 1006 (86%) and 956 (68%) (female) participants, respectively; >40% were ≥65 years, with individual lemborexant exposures derived from a previously described pharmacokinetic model. Linear mixed-effects analyses of polysomnography: latency to persistent sleep (LPS), sleep efficiency (SE), and wake after sleep onset (WASO) quantified the change from baseline given lemborexant exposure, time, and covariates, guided by consensus recommendations regarding clinical significance. A small impact of sex, body weight, and race was predicted for LPS and SE, irrespective of treatment. Effect of age on LPS was small; baseline SE was estimated to be 8% higher for a 50-year-old versus an 80-year-old, decreasing to 6% by 1 month. Baseline WASO was 13 minutes longer for Black versus White subjects, corresponding to a 5-minute lower change from baseline at the end of the study. For subjective end points, the statistically significant covariate effects for age, sex, and race were not deemed therapeutically relevant, likely reflecting physiologic sleep pattern changes across age and study subgroups. Both polysomnography and subjective analyses indicated clinically meaningful differences from baseline for both lemborexant treatments, with effects being greater for 10-mg versus 5-mg lemborexant, while indicating that covariate-specific lemborexant dose adjustments are not warranted.

Quick, easy, cheap, effective, rugged, and safe extraction strategies are becoming increasingly adopted in various analytical fields to determine drugs in biological specimens. In the present study, we developed two fully automated quick, easy, cheap, effective, rugged, and safe extraction methods based on acetonitrile salting-out assisted liquid-liquid extraction (method 1) and acetonitrile salting-out assisted liquid-liquid extraction followed by dispersive solid-phase extraction (method 2) using a commercially available automated liquid-liquid extraction system. We applied these methods to the extraction of 14 psychotropic drugs (11 benzodiazepines and carbamazepine, quetiapine, and zolpidem) from whole blood samples. Both methods prior to liquid chromatography-tandem mass spectrometry analysis exhibited high linearity of calibration curves (correlation coefficients, > 0.9997), ppt level detection sensitivities, and satisfactory precisions (< 8.6% relative standard deviation), accuracies (within ± 16% relative error), and matrix effects (81-111%). Method 1 provided higher recovery rates (80-91%) than method 2 (72-86%), whereas method 2 provided higher detection sensitivities (limits of detection, 0.003-0.094 ng/mL) than method 1 (0.025-0.47 ng/mL) owing to the effectiveness of its dispersive solid-phase extraction cleanup step. These fully automated extraction methods realize reliable, labor-saving, user-friendly, and hygienic extraction of target analytes from whole blood samples.

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.

In March 2020, the WHO announced the COVID-19 pandemic, which has been ongoing for over 2 years. To stop the spread of the virus, the governments of many countries decided to introduce reasonable social restrictions that were suitable for pandemic waves. This led to radical changes in people's lives, especially among students, who are very active in society. Before COVID-19, being of student age was associated with the highest frequency of stimulants use. It is important to note that drugs are taken disparately in various areas. Therefore, using the Computer-Assisted Web Interview type of study, the impact of the pandemic on the use of alcohol, cannabinoids, psychostimulants (e.g., amphetamine, methamphetamine, ecstasy) and sedatives (e.g., zolpidem, zopiclone, alprazolam, lorazepam, etc.) was assessed among students from European countries. The questionnaire included single- and multiple-answer questions. The first part concerned sociodemographic questions, while the second included questions about the use of stimulants in the last 3 months prior to participation in the study. Distribution of the survey covered the period from 31 January 2016 to 30 April 2021. A total of 17,594 European students participated in the study. The vast majority of participants were women (80.4%) and students of non-medical universities (77.2%) living in Eastern European countries (86.1%). Of all students, 15,613 (89.6%) reported alcohol drinking, 2538 (14.1%) the use of cannabinoids, 650 (3.6%) psychostimulants, and 2252 (12.5%) sedatives in the past three months. It has been shown that women are far less likely to use alcohol (OR 0.81), psychostimulants (OR 0.44) and cannabinoids (OR 0.49), while they are more likely to use sedatives (OR 1.41). During the COVID-19 pandemic, the consumption of alcohol (OR 0.55) and psychostimulants (OR 0.72) decreased and that of sleep medications increased (OR 1.17). To conclude, the COVID-19 pandemic influenced the pattern of stimulants used by students in European countries. The restriction of social interactions contributed to the decrease in the consumption of alcohol and psychostimulants but increased the use of sedatives and the frequency of their use. Women were found to use sedatives more often, while men preferred to drink alcohol and use cannabinoids or psychostimulants. It has also been shown that students of Central and Eastern Europe more often use alcohol and sedatives, while in Southern European countries psychostimulants and cannabinoids are preferred.

Zolpidem is indicated in cases of severe insomnia in adults and, as for BDZs, its assumption should be limited to short periods under close medical supervision. Since several drugs cause corrected QT interval (QTc) elongation, the authors investigated whether high daily doses of Zolpidem could cause QTc elongation. The study was conducted in the Addiction Medicine Unit of the G.B. Rossi University Hospital in Verona. The data were collected from hospitalizations carried out between January 2015 and February 2020 and refer to a total of 74 patients, 38 males and 36 females, who were treated for detoxification from high doses of Zolpidem with the "Verona Detox Approach With Flumazenil." One patient out of 74 had QTc elongation (479 ms). The patient was male and took a daily dose of 50 mg of Zolpidem; he did not take concomitant therapies that could cause QTc lengthening. He had no electrolyte alterations, no contemporary or previous intake of barbiturates, heroin, cocaine, THC, alcohol, NMDA or nicotine which could cause an elongation of the QTc interval. The present study highlights the low risk of QTc elongation due to high dosages of Zolpidem; however, if, on one hand, we can affirm that Zolpidem is a safe drug, on the other, the widespread use of high dosages of this drug for prolonged periods of time is problematic and worrying.

Background: Zolpidem is used for insomnia in pregnant and lactating women. Although zolpidem has been shown to cross the placenta and to be secreted into breast milk, it would not be expected to cause any adverse effects in newborn and breastfed infants. However, there is no relevant information on serum zolpidem levels in the newborn and breastfed infant from zolpidem-treated mother. This study aimed to present the outcomes of zolpidem exposure into infant who was delivered or breastfed by a zolpidem-treated mother. Methods: In this case series, zolpidem-treated pregnant women were recruited between September 2019 and April 2022, and maternal serum, cord blood, breast milk, and infants' serum were collected, and the zolpidem concentration in each sample was evaluated. Childbirth outcomes, including 1-month health care checkup, were also evaluated. Results: Three cases were recruited during investigation period. No spontaneous abortion or preterm live deliveries occurred. Oxygen intervention was required in one term infant, but the findings resolved on postpartum day 1. No medical intervention was required in other three infants. Zolpidem was not detected in infants' serum even after breastfeeding. There are no abnormal developmental findings in any of the infants in their 1-month health checkups. Conclusions: Zolpidem transferred into fetal circulation in utero and breast milk, however no harmful findings existed in infants during pregnancy and lactation. Exposure doses through breastfeeding is small, which may be a cause of rare detection from the infants' serum. Due to the limited number of cases, larger studies and integrated review are needed.

Herein, we report a highly efficient and unprecedented approach for heteroarylation of congested α-bromoamides via electrophilic aromatic substitution of imidazo-heteroarenes and indolizines under mild reaction conditions (room temperature, metal, and oxidant free). The participation of an in situ generated aza-oxyallyl cation as an alkylating agent is the hallmark of this transformation. The method was readily adapted to synthesize novel imidazo-heteroarene-fused dibenzoazepinone architectures of potential medicinal value.

Z-drugs, benzodiazepines and ketamine are classes of psychotropic drugs prescribed for treating anxiety, sleep disorders and depression with known side effects including an elevated risk of addiction and substance misuse. These drugs have a strong potential for misuse, which has escalated over the years and was hypothesized here to have been exacerbated during the COVID-19 pandemic. Wastewater-based epidemiology (WBE) constitutes a fast, easy, and relatively inexpensive approach to epidemiological surveys for understanding the incidence and frequency of uses of these drugs. In this study, we analyzed wastewater (n = 376) from 50 cities across the United States and Mexico from July to October 2020 to estimate drug use rates during a pandemic event. Both time and flow proportional composite and grab samples of untreated municipal wastewater were analyzed using solid-phase extraction followed by liquid chromatography-tandem mass spectrometry to determine loadings of alprazolam, clonazepam, diazepam, ketamine, lorazepam, nordiazepam, temazepam, zolpidem, and zaleplon in raw wastewater. Simultaneously, prescription data of the aforementioned drugs were extracted from the Medicaid database from 2019 to 2021. Results showed high detection frequencies of ketamine (90 %), lorazepam (87 %), clonazepam (76 %) and temazepam (73 %) across both Mexico and United States and comparatively lower detection frequencies for zaleplon (22 %), zolpidem (9 %), nordiazepam (<1 %), diazepam (<1 %), and alprazolam (<1 %) during the pandemic. Average mass consumption rates, estimated using WBE and reported in units of mg/day/1000 persons, ranged between 62 (temazepam) and 1100 (clonazepam) in the United States. Results obtained from the Medicaid database also showed a significant change (p < 0.05) in the prescription volume between the first quarter of 2019 (before the pandemic) and the first quarter of 2021 (pandemic event) for alprazolam, clonazepam and lorazepam. Study results include the first detections of zaleplon and zolpidem in wastewater from North America.

This sheet talks about exposure to zolpidem in a pregnancy and while breastfeeding. This information should not take the place of medical care and advice from your healthcare provider.