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Treatment of tremors, such as in essential tremor (ET) and Parkinson's disease (PD) is mostly ineffective. Exact tremor pathomechanisms are unknown and relevant animal models are missing. GABA-A receptor is a target for tremorolytic medications, but current non-selective drugs produce side effects and have safety liabilities. The aim of this study was a search for GABA-A subunit-specific tremorolytics using different tremor-generating mechanisms. Two selective positive allosteric modulators (PAMs) were tested. Zolpidem, targeting GABA-A α1, was not effective in models of harmaline-induced ET, pimozide- or tetrabenazine-induced tremulous jaw movements (TJMs), while the novel GABA-A α2/3 selective MP-III-024 significantly reduced both the harmaline-induced ET tremor and pimozide-induced TJMs. While zolpidem decreased the locomotor activity of the rats, MP-III-024 produced small increases. These results provide important new clues into tremor suppression mechanisms initiated by the enhancement of GABA-driven inhibition in pathways controlled by α2/3 but not α1 containing GABA-A receptors. Tremor suppression by MP-III-024 provides a compelling reason to consider selective PAMs targeting α2/3-containing GABA-A receptors as novel therapeutic drug targets for ET and PD-associated tremor. The possibility of the improved tolerability and safety of this mechanism over non-selective GABA potentiation provides an additional rationale to further pursue the selective α2/3 hypothesis. [ABSTRACT FROM AUTHOR]

Purpose: Poor sleep during hospitalization is common and implicated in worse patient outcomes. Despite implementation of non-pharmacologic techniques, medications are still frequently required. The study objective is to assess the frequency of new medications administered for sleep in hospitalized patients and to review literature evaluating these drug therapies in the inpatient setting. Methods: This retrospective study included adult inpatients if they received a new medication for sleep during a 5-day period. Patients were excluded if the medication was continued from home or if sleep was not the documented indication. For the literature review, a MEDLINE search was conducted to identify studies pertaining to pharmacotherapy for sleep in hospitalized patients. Results: Of 1,968 patient-days reviewed, a medication for sleep was given for 166 patient-days (8.4%) in 78 patients. Melatonin was most commonly received (70.5%), followed by benzodiazepines (9.6%). A review of antihistamines, benzodiazepines, melatonin, quetiapine, trazodone, and Z-drugs (non-benzodiazepine hypnotics) was conducted and 23 studies were included. Conclusions: Despite widespread use of pharmacotherapy for sleep, there is a paucity of data evaluating use in the inpatient setting. Although there is significant heterogeneity among studies, melatonin has the strongest evidence for use and is an attractive option given its lack of adverse reactions and drug interactions. Benzodiazepines and Z-drugs were also frequently utilized; however, their reduced clearance in the elderly and potential for compounded sedative effects should be weighed heavily against potential sleep benefits. Antipsychotic agents cannot be recommended for routine use due to limited data and the potential for significant adverse effects. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: An increased risk of fracture has been reported in older adults taking hypnotics. However, few studies have reported the comparative safety of hypnotics with different mechanisms of action. We examined the risk of fracture in older adults initiating suvorexant compared to those initiating Z‐drugs. Methods: We conducted a retrospective cohort study using a claims database within a longevity improvement and fair evidence (LIFE) study in Japan (1.5 million beneficiaries). People aged ≥65 years were included in this study. Exposure was defined as the initiation of either suvorexant or Z‐drugs (eszopiclone, zolpidem, or zopiclone). The evaluated outcomes were hip fracture and all‐cause fracture requiring hospitalization. We used inverse probability of treatment weights to adjust for confounding and followed the incidence of the outcome for three different periods: 30, 90, and 365 days. Cox proportional hazards models were fitted to the weighted population to estimate hazard ratios (HRs). Sensitivity analyses were performed with narrowed outcome definitions and inverse probability of censoring weights. Results: We identified 16,148 suvorexant new users and 54,327 Z‐drugs new users. During the 30‐day follow‐up, 21 (16.6 events per 1000 person‐years) and 53 hip fractures (12.2 events per 1000 person‐years) were identified among suvorexant and Z‐drugs new users, respectively (HR: 1.01, 95% confidence interval [CI]: 0.58–1.76). The analysis for all‐cause fracture showed an HR of 1.03 (95% CI: 0.78–1.36). Extended follow‐up (90 and 365 days) showed similar results for both outcomes. Sensitivity analyses showed consistent results except for an increased risk of all‐cause fracture requiring surgery (HR: 1.41, 95% CI: 0.87–2.29) during the 30‐day follow‐up. Conclusions: This is the first study to show that suvorexant has a generally comparable risk of fracture as compared to Z‐drugs. Further research is needed to investigate the potential short‐term increased risk of all‐cause fracture requiring surgery among suvorexant initiators. [ABSTRACT FROM AUTHOR]

Summary: Although more than one hundred studies have examined the prevalence of the use of benzodiazepines and benzodiazepine‐like Z‐hypnotics (BZDs) among pregnancy events, further analysis of the effects of dosage or type of BZDs is needed. The aim of this study was to examine the prevalence rate of BZDs use in pregnancy events, stratified by trimester over time, with characteristics of the dosage and type of BZDs. This is a retrospective population study based on linking three national databases. We examined the prevalence rates from 2004 to 2017, and contrasted the results based on >0 defined daily dose (DDD) and ≥0.5 DDD. We identified 2,630,944 pregnancy events with live births; 89,897 (3.4%) of the associated pregnancy events had used some form of BZD during pregnancy. The prevalence of BZDs use, as defined by >0 DDD, decreased from 4.1% in 2004 to 2.9% in 2017, indicating a decrease in sporadic use and an increase in stable use within therapeutic doses. Meanwhile, BZDs use defined by ≥0.5 DDD increased from 0.1% in 2004 to 0.4% in 2017. Zolpidem was the most frequently prescribed BZDs, as defined by >0 DDD or ≥0.5 DDD. This national cohort study demonstrates the importance of average dosage in the definition of BZDs use in pregnancy events, and it found opposite trends in the prevalence of use between different dosages. [ABSTRACT FROM AUTHOR]

After mild traumatic brain injury (mTBI), the brain is labile for weeks and months and vulnerable to repeated concussions. During this time, patients are exposed to everyday circumstances that, in themselves, affect brain metabolism and blood flow and neural processing. How commonplace activities interact with the injured brain is unknown. The present study in an animal model investigated the extent to which three commonly experienced exposures—daily caffeine usage, chronic sleep loss, and chronic sleep aid medication—affect the injured brain in the chronic phase. Subclinical trauma by repeated mTBIs was produced by our head rotational acceleration injury model, which causes brain injury consistent with the mechanism of concussion in humans. Forty-eight hours after a third mTBI, chronic administrations of caffeine, sleep restriction, or zolpidem (sedative hypnotic) began and were continued for 70 days. On Days 30 and 60 post injury, resting state functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) were performed. Chronic caffeine, sleep restriction, and zolpidem each changed the subclinical brain characteristics of mTBI at both 30 and 60 days post injury, detected by different MRI modalities. Each treatment caused microstructural alterations in DTI metrics in the insular cortex and retrosplenial cortex compared with mTBI, but also uniquely affected other gray and white matter regions. Zolpidem administration affected the largest number of individual structures in mTBI at both 30 and 60 days, and not necessarily toward normalization (sham treatment). Chronic sleep restriction changed local functional connectivity at 30 days in diametrical opposition to chronic caffeine ingestion, and both treatment outcomes were different from sham, mTBI-only and zolpidem comparisons. The results indicate that commonly encountered exposures modify subclinical brain activity and structure long after healing is expected to be complete. Changes in activity and structure detected by fMRI are widely understood to reflect changes in the functions of the affected region which conceivably underlie mTBI neuropathology and symptomatology in the chronic phase after injury. • Chronic exposures to common real-life situations modify the concussed brain. • The effects of chronic exposures in mTBI are heterogeneous and evolve over time. • Chronic exposures affect the brain uniquely, detected by different fMRI parameters. • Chronic sleep loss and caffeine in mTBI have opposing effects on local connectivity. • Zolpidem in mTBI disturbed brain microstructure but not local connectivity. [ABSTRACT FROM AUTHOR]

With rapid expansion of cannabis legalization worldwide, rates of cannabis use and cannabis use disorder (CUD) are increasing; the need for safe and effective medications to treat CUD is urgent. This narrative review evaluates evidence for promising pharmacotherapies to treat CUD from randomized, placebo-controlled trials. Pharmacotherapies for CUD are categorized based on compound targets (e.g., cannabinoid receptor 1 [CB1] agonists such as nabilone, serotonergic compounds such as bupropion, GABAergic compounds such as zolpidem) and outcomes are organized by predetermined withdrawal symptoms, cannabis craving, and cannabis relapse/use. Most promising pharmacotherapies for CUD are drugs that act on the endocannabinoid system and specifically at the CB1 receptor. Priority populations such as females, certain racial/ethnic groups, and age groups experience a different course of CUD progression, symptoms, and drug effects that are important to consider when evaluating outcomes related to CUD. Possible explanations for these disparities are explored, along with the clinical trials that explore these demographics in treating CUD with pharmacotherapies. [ABSTRACT FROM AUTHOR]

Estimation of drug ingestion time (event time) and distinguishing between drug ingestion and external contamination are important for interpreting hair analysis results in forensics practice. Here, we present a matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) method for in situ analysis of intact hair. We applied a longitudinal cutting method for a single hair to analysis authentic hair samples from a victim of a drug-facilitated sexual assault (DFSA) case and zolpidem-soaked hair. MALDI-MSI showed that zolpidem-positive segments distributed at 4−6 mm or 6−8 mm from the root in three single hairs of a DFSA victim collected 25 days after the event, at concentrations ranging from 0.1 to 5.7 pg mm−1, in agreement with the results from segmental analysis using liquid chromatography tandem mass spectrometry (LC-MS/MS). The estimation of drug intake time was about 20–30 days before sampling, which was consistent with the known time of drug intake. This MALDI-MS method allows imaging analysis of trace substances in a single hair and can realize the intuitive reflection of drug taking time. In addition, zolpidem applied by soaking was mainly distributed on both sides of the longitudinal hair shaft, whereas ingested zolpidem was found only in the middle of the hair shaft of the DFSA victim. The MALDI-MS images of unwashed and washed hair suggested that the amount of externally applied drug was decreased by washing, it was still present on surface layer (cuticle) sides although. Visualization using MALDI-MSI could therefore distinguish between drug ingestion and contamination by reflecting the distribution and deposition site of the drug in hair. • A longitudinal cutting and MALDI-MS method of single hair was established. • The established method can realize the intuitive reflection of drug taking time. • The method can distinguish between drug ingestion and contamination of hair. [ABSTRACT FROM AUTHOR]

Abstract Background Z-drugs are usually prescribed as first line pharmacological therapy for insomnia. However, the benefits and risks of Z-drugs may differ for older adults. This systematic review investigated the available evidence on the efficacy and safety of Z-drugs in the management of insomnia in older adults. Methods The Cochrane database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, PubMed/MEDLINE and EMBASE were searched for systematic reviews, meta-analyses, controlled interventional and observational studies using a pre-formulated search term. The target population was older adults (≥65 years old) with insomnia. Studies were included if they reported efficacy and/or safety outcomes of the use of Z-drugs for the management of insomnia compared to placebo, usual or no treatment, or other pharmacological agents. Results Eighteen studies were included (8 interventional and 10 observational studies). In short-term interventional studies, Z-drugs were similarly or better efficacious in improving both sleep and daytime parameters than placebo or other pharmacological treatments, while showing good results on measures of safety. However, in longer-term observational studies, Z-drugs significantly increased the risk for falls and fractures in comparison to no treatment or melatonin agonists. Conclusions Analyzing the evidence from short-term interventional studies, Z-drugs appear effective and safe for treatment of insomnia in older adults, but they may have unfavorable side effects when used for longer periods of time. We, therefore, recommend discontinuing Z-drugs, principally because of the high risk for falls and fractures. Nonetheless, quality and quantity of evidence are low. Due to the scarcity of data, especially concerning drug dependence after longer periods of treatment and due to the significantly increased risk for falls and fractures, further studies are needed to evaluate the benefit-risk profile of Z-drugs use in older patients, particularly for long-term use.

Background: A constituent of diffuse axonal injury (DAI) is supposed to be present in about 1/3 of all severe traumatic brain injury (TBI) as specified by pathologic documents. Diffuse axonal injury is categorized by extensive injury to axons in the brain. A rise in the incidences of TBI, and the limited study to verified effect of drugs like amantadine and zolpidem in improving the consciousness levels of patients with acute traumatic brain injury with axonal injury enthused us to initiate this study in the acute TBI patients. Methods: In our randomized, controlled trial involving patients with acute severe TBI, we studied 66 patients in 3 groups. Group 1 (n=22) received oral amantadine, Group 2 (n=22) received oral zolpidem, whereas group 3 (n=22) received placebo, the first 8 days after injury respectively. The primary outcome measures included GCS (Glashow coma scale) through the initial admission, a complete medical history was recorded, and each patient had a meticulous physical and neurological investigation. Results: We found that the administration of amantadine in an acute phase after injury improved the rate of patients GCS and GOS (Glasgow Outcome Scale) compared with zolpidem and placebo groups, but without any significant statistical difference. Conclusion: Our results has emphasized that because amantadine has intense biochemical effects on several ways, it appears to be beneficial in acute period after DAI-associated TBI.

Background: Z-drugs (zopiclone, zaleplon, and zolpidem) are commonly prescribed medicine classes associated with a risk of abuse, dependence or withdrawal. Objective: The purpose of our work is to review the current knowledge on the evidence for z-drugs harms and estimate the prevalence of dispensed prescriptions. Material and Methods: A literature review was conducted in PubMed database using the key words: “Zolpidem”, “Z-drugs”, “Abuse”, “Dependence” Results: According to our findings, zolpidem should be prescribed with the same caution as BZDs, especially in patients with a history of drug abuse or in the elderly. Conclusion: Psychiatrists and physicians should be aware of the misuse potential of zolpidem and adopt measures restricting its use.

The brain is one of the most sensitive organs to hypoxia and the most vulnerable to ischemia and vascular events. Zolpidem, as a GABA-A receptor agonist, has an inhibiting effect on the central nervous system. In this study, the possible side effects of zolpidem on brain perfusion were reported in a patient with zolpidem addiction. Moreover, the correlated literature has been reviewed. The patient was a 33-year-old man who was referred with a complaint of cognitive impairment, gait disturbance, confusion, and seizure. The patient reported taking the daily dose of 270 mg of zolpidem. He developed acute dystonia, rigidity, and bradykinesia during treatment with haloperidol in the psychiatric ward. Brain MRI and EEG were requested due to the prolongation of cognitive impairment and parkinsonism symptoms. The Neurologist utilized Brain MRA to determine the source of microvascular lesions found in the brain MRI. Unexpectedly, a reduction in Anterior Cerebral Artery (ACA) perfusion was detected after a comprehensive evaluation by Brain MRA. In addition, impairment of several cognitive domains was observed in the follow-up visit. Zolpidem could reduce cerebral perfusion in various vascular territories. It seems that in patients who take zolpidem with higher than therapeutic doses, vascular complications and a decreased cerebral perfusion have occurred, resulting in more neurological complications, including cognitive disorders and vascular events. A holistic investigation of the patient with zolpidem abuse and neurological symptoms would be recommended to determine the probable vascular complication of zolpidem.

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Purpose. Insomnia is the most common sleep disorder with high rate of prevalence, persistence, and leads to negative consequences. The mainstays of insomnia treatment have limitations due to either the side effects of hypnotics or limited accessibility to cognitive behavioral therapy. This study aims to compare the efficacy and safety of the traditional Chinese medicine (TCM) Zaoren Anshen capsule alone or as an adjunct treatment with different doses of the nonbenzodiazepine medication zolpidem tartrate in treating insomnia. Method. This randomized, double-blind, multicentre placebo control trial was conducted in 131 patients with chronic insomnia. The patients were randomly assigned to one of the following four regimen groups: Group ZA + Z5 : Zaoren Anshen capsule and 5 mg zolpidem tartrate (n = 32); Group Z5: 5 mg zolpidem tartrate and placebo capsule (n = 35); Group Z10 : 10 mg zolpidem tartrate and placebo capsule (n = 32); Group ZA : Zaoren Anshen capsule and placebo pill (n = 32). The drugs were administered for 4 weeks. All patients were evaluated by the Insomnia Severity Index (ISI) at 0, 2, 4, 5, and 6 weeks, and adverse events were recorded. Result. There are significant differences in the comparison between the four groups at each treatment stage (P < 0.05). Repeated measurement analysis of variance (ANOVA) of ISI scores in each treatment stage of the four groups exhibits significant differences in time effect, intergroup effect, and interaction effect (P < 0.05). After four weeks of drug administration, the treatment efficacy is similar in Groups ZA + Z5 and Z10 (93%) and in Groups Z5 and ZA (62% and 65%, respectively). Groups ZA + Z5 and Z10 present significantly lower ISI scores compared with Groups Z5 and ZA (P < 0.05), which indicates better treatment response of Groups ZA + Z5 and Z10. No significant difference was observed in the incidence of adverse events between the groups. Conclusion. Zaoren Anshen capsule can effectively treat insomnia disorder either alone or in combination with zolpidem tartrate. A preferred combination of TCM Zaoren Anshen capsule with zolpidem can provide a magnified therapeutic efficacy with fewer side effects than zolpidem-only management, clinical trial registration number: Chinese Clinical Trial Registry ChiCTR-IPR-1600969. [ABSTRACT FROM AUTHOR]

Inherited mitochondrial optic neuropathies, such as Leber's hereditary optic neuropathy (LHON) and Autosomal dominant optic atrophy (ADOA) are caused by mutant mitochondrial proteins that lead to defects in mitochondrial complex 1-driven ATP synthesis, and cause specific retinal ganglion cell (RGC) loss. Complex 1 defects also occur in patients with primary open angle glaucoma (POAG), in which there is specific RGC loss. The treatment of mitochondrial optic neuropathy in the US is only supportive. The Ndufs4 knockout (Ndufs4 KO) mouse is a mitochondrial complex 1-deficient model that leads to RGC loss and rapid vision loss and allows for streamlined testing of potential therapeutics. Preceding RGC loss in the Ndufs4 KO is the loss of starburst amacrine cells, which may be an important target in the mechanism of complex 1-deficient vision loss. Papaverine and zolpidem were recently shown to be protective of bioenergetic loss in cell models of optic neuropathy. Treatment of Ndufs4 KO mice with papaverine, zolpidem, and rapamycin-suppressed inflammation, prevented cell death, and protected from vision loss. Thus, in the Ndufs4 KO mouse model of mitochondrial optic neuropathy, papaverine and zolpidem provided significant protection from multiple pathophysiological features, and as approved drugs in wide human use could be considered for the novel indication of human optic neuropathy.

Zolpidem (ZOL) is a short-acting hypnotic that is sometimes used in drug-facilitated crimes such as sexual assaults, robbery and homicides. Therefore, it is important to understand the metabolism of ZOL. This study quantified ZOL and its metabolites, including two carboxylic acids (zolpidem phenyl-4-carboxylic acid [M1] and 6-carboxylic acid [M2]) and four hydroxyzolpidems (4-(hydroxymethyl)phenyl zolpidem [M3], 6-hydroxymethyl zolpidem [M4], 7-hydroxyzolpidem [7OH] and 8-hydroxyzolpidem [8OH]) in postmortem urine using liquid chromatography--triple quadrupole mass spectrometry. The concentration of M1 was highest in all cases, followed by total 7OH in five of six samples. The concentrations of M2 and total M4 were relatively high. Most of M4 and 8OH were excreted as conjugates, whereas up to 55% of 7OH was excreted in its free form. Peaks corresponding to zolpidem dihydrodiol (ZHDH), dihydro(hydroxy)zolpidem cysteine adduct (DHZCys) and zolpidem cysteine adduct (ZCys) were also detected in all the urine samples. ZDHD was excreted as conjugates, whereas almost all DHZCys and ZCys were in their free form. [ABSTRACT FROM AUTHOR]

Daridorexant is a new sleep medication with a different mode of action than, for instance, benzodiazepine. Daridorexant is a so-called dual orexin receptor antagonist (DORA), which within the complex process of falling asleep is said to reduce wakefulness and increase somnolence. Hardly any research has been conducted into the efficacy of daridorexant compared with non-medicinal treatments, like cognitive behavioural therapy, or treatment with benzodiazepine agonists. It is unclear, for instance, whether it results in less daytime sleepiness than the benzodiazepine agonists, but it does affect driving performance on the day after administration of a single dose. The question is whether this new sleeping pill nevertheless has any added value over existing treatments. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Lemborexant has demonstrated statistically significant improvements in sleep onset and sleep maintenance compared with placebo and zolpidem tartrate extended release, measured both objectively using polysomnography and subjectively using sleep diaries, in the phase 3 clinical trial SUNRISE 1. This study evaluated the cost-effectiveness of lemborexant compared with suvorexant, zolpidem immediate release (IR), and untreated insomnia. Methods: A decision-tree model was developed for falls, motor vehicle collisions, and workplace accidents associated with insomnia and insomnia treatments from a Japanese healthcare perspective and with a 6-month time horizon. The model extracted subjective sleep onset latency treatment responses and disutility values for non-responders from SUNRISE 1. Cost-effectiveness was assessed using incremental cost per quality-adjusted life year (QALY) gained. One-way and probabilistic sensitivity analyses were conducted to evaluate the impact of parameter uncertainty on the results. Results: In the base-case analysis, the mean estimated QALYs for lemborexant, suvorexant, zolpidem-IR, and untreated insomnia were 0.4220, 0.4204, 0.4113, and 0.4163, and expected medical costs were JPY 34 034, JPY 38 371, JPY 38 139, and JPY 15 383, respectively. Lemborexant saved JPY 4337 and JPY 4105 compared with suvorexant or zolpidem-IR, respectively, while conferring QALY benefits. The incremental cost-effectiveness ratio (ICER) of lemborexant compared with that of untreated insomnia was JPY 3 220 975 /QALY. Lemborexant was dominant over suvorexant and zolpidem-IR and was cost-effective when compared with untreated insomnia. Sensitivity analyses supported the results' robustness. Conclusions: In a Japanese clinical practice setting, lemborexant may represent a better investment for treating insomnia in the healthcare system in Japan. [ABSTRACT FROM AUTHOR]

Applied entomotoxicology is the study of toxicants found in carrion insects and other matter, such as frass especially when body fluids or tissues cannot be used. The use of necropsy insects in medical and criminal investigations to detect toxicants has been done successfully. This study investigated the effect of the sedative drug zolpedim tartrate on the developmental rate and morphological parameters of the feeding and non‐feeding stages of the carrion insect Sarcophaga peregrina Robineau‐Desvoidy. Five cultures were prepared‐one control and four cultures containing different concentrations of zolpidem tartrate (1, 2, 3, and 4 ppm). A total of 80 larvae were kept in each culture and provided with finely chopped liver containing the respective concentrations daily. The results obtained showed significant variations in the morphological parameters of the feeding and non‐feeding stages, and negatively correlated with the concentrations compared with the control. The developmental time of the feeding and non‐feeding stages positively correlated with the concentration of zolpidem tartrate. The results obtained indicate that zolpidem tartrate retards larval development and alters the estimation of the total developmental duration. When analyzing the entomological evidence of whether zolpidem tartrate may be responsible for death, it is important to consider its effects on PMI estimation. [ABSTRACT FROM AUTHOR]

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Introduction: Current hypnotic agents have next‐day residual effects. The new orexin antagonist, suvorexant, has little muscle relaxation effect on the physical and cognitive function in the following morning and daytime. In this study, the effects of suvorexant, zolpidem, ramelteon and placebo in elderly subjects were evaluated. Methods: Six men and eight women aged 63–75 years received a single tablet and lights were then turned off. Subjects were instructed to sleep from 23:00–6:00 with an interruption from 4:00–4:30 for evaluations. Suvorexant 10 mg, zolpidem 5 mg, ramelteon 4 mg or placebo was administered single time in a randomized, double‐blind and crossover design with a one‐week drug holiday in between each drug. Measures of objective parameters and subjective ratings were obtained every 2 h from 4:00 to 16:00. Result: No subjects showed serious side effects from physical observations and vital sign checks before and after hypnotics were taken. During the first sleep period, the REM sleep time with suvorexant was especially longer than that with zolpidem. During the second sleep period, suvorexant had shorter sleep latency and longer stage2 sleep time than ramelteon and zolpidem, respectively. During the whole entire sleep, the REM sleep time with suvorexant was longer than zolpidem and placebo. For the body sway test with closed eye, the main effects of the medicines and zolpidem were significantly better than suvorexant and ramelteon. Conclusion: The changes of physical and cognitive functions in healthy elderly after taking hypnotics were not remarkable. Therefore, these three hypnotics maybe appropriate for the elderly people with insomnia for single‐time low dose administration. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to investigate the efficacy of zolpidem for improving post-operative sleep quality among patients with infective endocarditis (IE) and to identify the potential risk factors for impaired sleep quality at 6 months after surgery. Methods: Patients with IE who underwent surgical treatment were divided into two groups according to zolpidem usage. The Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were used to evaluate patients' sleep quality and daytime sleepiness at baseline, which was the second day after transferal, and at 6 months after surgery. Logistic regression was used to identify potential risk factors. Results: There were 32 patients in the zolpidem group and 42 in the control group. The PSQI and ESS scores at 6 months after surgery were significantly lower than those at baseline in both groups (P = 0.04). Additionally, 9 patients (28%) in the zolpidem group and 22 patients (52%) in the control group suffered poor sleep quality. Multivariate analysis identified age (odds ratio [OR] = 1.26, 95% confidence interval [CI]: 1.12–1.42), baseline PSQI score (OR = 2.66, 95%CI: 1.55–4.65), and no zolpidem usage (OR = 45.48, 95%CI: 3.01–691.23) as independent factors for poor sleep quality. Conclusions: Poor sleep quality after IE surgery was prevalent among patients even 6 months after IE surgery. Age, baseline PSQI score and no zolpidem usage were independently associated with poor sleep quality. Therefore, zolpidem has the potential to be an effective part of a treatment arsenal for poor sleep quality after surgical treatment for IE. [ABSTRACT FROM AUTHOR]

Background: Catatonia is a psychomotor syndrome associated with neurotransmitter disturbances, common in both psychiatric and medical settings. Hypoactivity of the GABA A receptor is one of the predominant theories behind the pathophysiology of catatonia, affecting both motor functioning and emotional regulation. Benzodiazepines such as lorazepam are considered the first-line treatment for catatonia. However, up to 27% of catatonia cases fail to respond to benzodiazepines alone. Zolpidem, which can be used as a challenge, monotherapy, or augmentation agent, serves as a promising pharmacological agent for catatonia due to its unique pharmacodynamic and pharmacokinetic profile., Objective: We sought to systematically examine the evidence behind zolpidem's use among adult patients to understand its clinical utility in the management of catatonia against prevailing treatments such as lorazepam and electroconvulsive therapy (ECT)., Methods: We conducted a systematic review using search terms related to zolpidem and catatonia in PubMed, EMBASE, and Web of Science. We followed PRISMA guidelines and identified 29 studies, including case studies and case series, that met inclusion criteria., Results: We reviewed 35 cases in which zolpidem was used for catatonia management (age: M =51.5 ± 21.0 SD years; 68.6% female; Bush Francis Catatonia Rating Scale: M=22.2 ± 9.0 SD). Proportions of positive responses for zolpidem on catatonia varied by treatment approach: 91% as a challenge agent (n=10), 100% as a first-line monotherapy agent (n=3), 57% as a first-line combination therapy agent (n=4), 70% as a second-line monotherapy agent (n=7), and 100% as a second-line augmentation agent (n=4). In total, 28 out of the 35 reported cases of catatonia (80%) responded positively to zolpidem., Conclusions: An 80% positive response rate for zolpidem in lysing catatonia is encouraging but may be an overestimate due to reporting bias of case level data. Results may be explained by zolpidem's selectivity for the α 1 subunit of the GABA A receptor. Thus, zolpidem may be an under-utilized catatonia treatment and prove useful in situations when benzodiazepines fail or when ECT access is limited. Given that current literature on the use of zolpidem for catatonia is limited to case reports, more robust research in this area is warranted., (Copyright © 2024 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: The efficacy and safety of zolpidem for treating musician's dystonia are not well understood. We aimed to retrospectively investigate the efficacy and safety of zolpidem for treating musician's dystonia., Methods: We retrospectively reviewed medical records between January 2021 and December 2023 to identify patients with musician's dystonia who had been prescribed zolpidem. Tubiana's Musician's Dystonia Rating Scale (range, 1-5; lower scores indicating greater severity) was used to evaluate musician's dystonia., Results: Fifteen patients were included in this study. The mean effective dose of zolpidem was 5.3 ± 2.0 mg. The mean effective duration of zolpidem was 4.3 ± 1.2 h. With zolpidem administration, Tubiana's musician's dystonia rating scale score significantly improved from 2.2 ± 1.0 to 4.3 ± 0.8 (48.9% improvement, p < 0.001). Two patients (13.3%) discontinued the drug owing to unsatisfactory results or sleepiness., Conclusion: The results of this study suggest that zolpidem may be an alternative treatment option for musician's dystonia.

ABSTRACT. Zolpidem is one of the most widely prescribed hypnotic (non-benzodiazepine) agents for sleep disorder. Recently, an increase in the demand for this drug has been observed, mainly in the elderly population. Objective: This study aims to analyze the acute effect of zolpidem on cognitive and balance dysfunctions in the elderly population. Methods: A study was conducted by two independent researchers in four virtual scientific information bases and included randomized controlled trials. The studies evaluated elderly patients using zolpidem. Cognitive and balance dysfunctions were analyzed. Results: Six articles were included. The mean age of the participants in the studies was 69 years. The following zolpidem dosages were evaluated: 5, 6.25, 10, and 12.5 mg. Comparing zolpidem and placebo, relating to the cognitive dysfunctions, there is no statistically significant difference between the groups. However, in relation to balance dysfunctions, there is a statistically significant difference between the intervention and the comparison, favoring placebo. Conclusions: Zolpidem, even in usual doses (5 mg and 10 mg), has shown to increase the risk for balance dysfunctions. However, this does not occur in relation to cognitive changes.

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.