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Medicines associated with dependence or withdrawal: a mixed-methods public health review and national database study in England.

BACKGROUND: Antidepressants, opioids for non-cancer pain, gabapentinoids (gabapentin and pregabalin), benzodiazepines, and Z-drugs (zopiclone, zaleplon, and zolpidem) are commonly prescribed medicine classes associated with a risk of dependence or withdrawal. We aimed to review the evidence for these harms and estimate the prevalence of dispensed prescriptions, their geographical distribution, and duration of continuous receipt using all patient-linked prescription data in England. METHODS: This was a mixed-methods public health review, comprising a rapid evidence assessment of articles (Jan …

Use of benzodiazepines and z-drugs not compliant with guidelines and associated factors: a population-based study.

Benzodiazepines and z-drugs are primarily indicated for the treatment of sleep disorders and anxiety symptoms. Their frequent long-term use contrasts with the international guidelines that limit treatment duration to a maximum of 4 weeks. The objective of this study was to assess the frequency of their use that was not in accordance with guidelines in the French general population between 2007 and 2012 and associated characteristics. A cohort of 67,550 benzodiazepine new users was set up in an exhaustive database for health-care reimbursements and representative of the French population. Benzo

Relative picrotoxin insensitivity distinguishes ionotropic GABA receptor-mediated IPSCs in hippocampal interneurons.

Inhibitory GABAergic signalling in the hippocampus plays an important role in synchronizing principal cells and regulating the excitability of this seizure-prone structure. Distinct mechanisms modulate release from GABAergic terminals in the hippocampus, depending on whether the postsynaptic partner is an interneuron or a principal cell. Here, we report that postsynaptic ionotropic GABA receptors in principal cells and interneurons also show a striking pharmacological difference. The broad-spectrum antagonist picrotoxin (PTX) was less potent at blocking IPSCs evoked in stratum radiatum interne

Emergency department visits by adults for psychiatric medication adverse events.

IMPORTANCE: In 2011, an estimated 26.8 million US adults used prescription medications for mental illness. OBJECTIVE: To estimate the numbe … 2.3-3.5) for stimulants, and 2.4 (95% CI, 2.1-2.7) for antidepressants. The commonly used sedative zolpidem tartrate was implicated in 11.5% (95% CI, 9.5%-13.4%) of all adult psychiatric medication ADE ED visits and in 21.0% (95% CI, 16.3%-25.7%) of visits involving adults 65 years or older, in both cases significantly more than any other psychiatric medi …

Determination of 19 drugs of abuse and metabolites in whole blood by high-performance liquid chromatography-tandem mass spectrometry.

A high-performance liquid chromatography (LC)-tandem mass spectrometry (MS/MS) method has been developed and validated for the determination of 19 drugs of abuse and metabolites and used in whole blood. The following compounds were included: amphetamine, methylenedioxyamphetamine, methylenedioxyethylamphetamine, methylenedioxymethamphetamine, methamphetamine, cocaine, benzoylecgonine, morphine, 6-acetylmorphine, codeine, methadone, buprenorphine, norbuprenorphine, ketobemidone, tramadol, O-desmethyltramadol, zaleplone, zolpidem, and zopiclone. The sample pretreatment consisted of solid-phase e…

Evaluating the utility of melatonin in spine surgery: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Spine surgery is increasingly performed worldwide, and acute postoperative stressors such as pain and anxiety remain highly prev … ; BMI=28.5±4.3 kg/m2), and active pharmacologic comparators (fentanyl, gabapentin, dexmedetomidine, zolpidem) to 151 patients (age=46.6±8.9 years; 40.5% male; BMI=26.3±3.5 kg/m2). Procedures primarily involved uncomplicated lumbar laminectomies (1-4 levels), with outcomes assessed up to 24 hours postoperatively. Melatonin was associated with significant im …

Analysis of the Prevalence of Alcohol and Psychoactive Substances Among Drivers in the Material from the Department of Forensic Medicine at the Medical University of Bialystok in Poland.

In recent years, the issue of drivers under the influence of medications and psychoactive substances as a cause of road accidents has gained … ephedrone 37.5 ng/mL; alfa-PVP 120 ng/mL), psychotropic drugs-3.1% (carbamazepine 8.0-2100.0 ng/mL; zolpidem 233.0 ng/mL; citalopram 320.0 ng/mL; opipramol 220 ng/mL). The most commonly used substance among car and motorcycle drivers was THC (37.7% of car drivers and 60% of motorcyclists). Among operators of other types of vehicles, alcohol was the most fr …

A scoping review of motor vehicle operator performance assessments for benzodiazepine receptor agonists.

BACKGROUND: Benzodiazepines and Z-drugs (e.g., zopiclone, zolpidem) (benzodiazepine receptor agonists or BZRAs), are prescribed for anxiety and insomnia disorders. However, they are not indicated as first line therapies for long-term management due to harms and efficacy limitations. BZRAs have also been associated with traffic accident risks. Patients taking BZRAs are told to consult with health care providers regarding motor vehicle operation safety. However, advice on driving is variable. The objective of this scoping review is to identify, map, and characterize the evidence for assessments …

Single-Cell Meta-Analysis of Neutrophil Activation in Kawasaki Disease and Multisystem Inflammatory Syndrome in Children Reveals Potential Shared Immunological Drivers.

BACKGROUND: Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) share similar clinical manifestations, including … tration-approved drugs methotrexate, zaleplon, metronidazole, lorazepam, clonazepam, temazepam, and zolpidem, among others, are primary candidates for drug repurposing. CONCLUSIONS: Our findings indicate that CD177+ neutrophils may exert systemic pathological damage contributing to the shared morbidities in KD and MIS-C. We uncovered potential regulatory …

Dihydromyricetin prevents fetal alcohol exposure-induced behavioral and physiological deficits: the roles of GABAA receptors in adolescence.

Fetal alcohol exposure (FAE) can lead to a variety of behavioral and physiological disturbances later in life. Understanding how alcohol (et … c miniature inhibitory postsynaptic currents (mIPSCs) and tonic current (Itonic) to potentiation by zolpidem (0.3 μM). Interestingly, potentiation of mIPSCs by gaboxadol increased, while potentiation of Itonic decreased in DGCs from FAE rats. Co-administration of EtOH (1.5 or 2.5 g/kg) with DHM (1.0 mg/kg) in pregnant dams prevented all of the behavioral, …

Hypnosedative-induced complex behaviours : incidence, mechanisms and management.

A number of news items and case reports describing complex behaviours (e.g. sleep driving, sleep cooking, sleep eating, sleep conversations, … rs involving 17 unique patients. Fifteen of the 17 patients described in the case reports had taken zolpidem, one had taken zaleplon and one had taken zopiclone. The complex behaviours most commonly reported were sleep eating, sleepwalking with object manipulation, sleep conversations, sleep driving, sleep sex and sleep shopping. Elevated serum concentrati …

Do subtype-selective gamma-aminobutyric acid A receptor modulators have a reduced propensity to induce physical dependence in mice?

Recent evidence suggests that GABA(A) receptors containing an alpha1 subunit mediate the sedative effect of diazepam, whereas receptors with an alpha2 subunit mediate this benzodiazepine's anxiolytic effect. Thus, compounds selective for GABA(A)-alpha2 receptors may offer advantages, i.e., lack of sedation, over current benzodiazepines. Whether such compounds would offer additional advantages over benzodiazepines is unclear. Here, we address the issue of physical dependence by comparing the GABA(A)-alpha1 affinity-selective drug zolpidem, the novel compounds 7-(1,1-dimethylethyl)-6-(2-methyl-2…

Review of Safety and Efficacy of Sleep Medicines in Older Adults.

PURPOSE: Insomnia is problematic for older adults. After behavioral modifications fail to show adequate response, pharmacologic options are … am, temazepam, flurazepam, and quazepam), nonbenzodiazepine receptor agonists (non-BzRAs; zaleplon, zolpidem, and eszopiclone), suvorexant, ramelteon, doxepin and trazodone. Off-label drugs such as other antidepressants, antihistamines, antipsychotics, gabapentin, pramipexole, tiagabine, valerian, and melatonin were also included. FINDINGS: Cognitive beha …

Medication use and functional status decline in older adults: a narrative review.

BACKGROUND: Functional status is the cornerstone of geriatric care and serves as an indicator of general well-being. A decline in function c … a study of hospitalized rehabilitation patients, users of hypnotics/anxiolytics (eg, phenobarbital, zolpidem) had lower relative Functional Independence Measure motor gains than nonusers. Use of multiple central nervous system (CNS) drugs (using different definitions) was linked to greater declines in self-reported mobility and Short Physical Performance B …

Sleep complaints: Whenever possible, avoid the use of sleeping pills.

(1) Most sleep complaints involve difficulties in getting to sleep or staying asleep, or not feeling refreshed on awakening. Misconceptions … ures and road accidents, and a withdrawal syndrome after treatment cessation. Related drugs such as zolpidem and zopiclone provoke similar adverse effects; (8) Sedative antihistamines have not been as well-evaluated as benzodiazepines in this setting. Small comparative trials of doxylamine and diphenhydramine showed no major difference in efficacy versus b …

Eszopiclone, a nonbenzodiazepine sedative-hypnotic agent for the treatment of transient and chronic insomnia.

OBJECTIVE: This paper reviews the pharmacologic and pharmacokinetic properties, clinical efficacy, and safety profile of the nonbenzodiazepi … somnia. In the absence of published studies comparing eszopiclone with similar hypnotic agents (eg, zolpidem, zaleplon, zopiclone), it is not yet possible to evaluate its efficacy relative to other agents used for insomnia.

Zaleplon: a review of its use in the treatment of insomnia.

Zaleplon is a pyrazolopyrimidine hypnotic agent which is indicated for the short term (2 to 4 weeks) management of insomnia. Zaleplon 5 and … lly did not improve. The relative hypnotic efficacy of zaleplon compared with that of triazolam and zolpidem is not yet clearly established. Tolerance to the hypnotic effects of zaleplon generally did not occur during 5 weeks' treatment, or during long term treatment (6 or 12 months) according to a small number of studies presented as abstracts. Zaleplon w …

Prescription and use of psychoactive medications among cancer patients and associated factors in lower and upper middle-income countries: systematic review.

PURPOSE: To describe the prescription and use of psychoactive medications among cancer patients in low- and middle-income countries (LMICs) and explore the factors influencing their prescription and use. METHODS: This systematic review was conducted following the PRISMA guidelines. Six electronic databases were searched. We included observational studies that investigated the prescription and use of psychoactive medications among adult cancer patients in low- and middle-income countries (LMICs) according to the 2024 World Bank's classification. Eligible studies specifically focused on the use

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… Other related drugs, such as zolpidem and zopiclone, were also used for insomnia. … *Eszopiclone, Zolpidem One of the most common potentially inappropriate medication used were benzodiazepines and Z-drug hypnotics, accounting for 27.7% of all identified PIMs ( n = 2427) NI Machado et al., 2022 Brazil n = 153 (Patients with multiple myeloma and treated in the oncology and hematology …

A 2-week, polysomnographic, safety study of sodium oxybate in obstructive sleep apnea syndrome.

PURPOSE: Sodium oxybate (SXB) is approved for cataplexy and excessive daytime sleepiness in narcolepsy. Obstructive sleep apnea syndrome (OSAS) affects ∼9-50% of narcoleptics. Effects of 2-week SXB administration on apnea-hypopnea index (AHI), oxygen saturation (SaO(2)), and sleep architecture were investigated in OSAS patients. METHODS: OSAS patients (n = 48) received 2-week SXB or placebo (PBO) treatment with polysomnography at baseline and day 14. The primary outcome measure was change from baseline in mean AHI. Secondary outcomes included changes from baseline in SaO(2), and sleep archite