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Sleep Nov 2023
Topics: Humans; Zolpidem; Sleep Initiation and Maintenance Disorders; Pyridines; Hypnotics and Sedatives; Behavior Therapy; Double-Blind Method
PubMed: 37691423
DOI: 10.1093/sleep/zsad240 -
BMC Pharmacology & Toxicology Jul 2015Long-term sedative use is prevalent and associated with significant morbidity, including adverse events such as falls, cognitive impairment, and sedation. The... (Review)
Review
BACKGROUND
Long-term sedative use is prevalent and associated with significant morbidity, including adverse events such as falls, cognitive impairment, and sedation. The development of dependence can pose significant challenges when discontinuation is attempted as withdrawal symptoms often develop. We conducted a scoping review to map and characterize the literature and determine opportunities for future research regarding deprescribing strategies for long-term benzodiazepine and Z-drug (zopiclone, zolpidem, and zaleplon) use in community-dwelling adults.
METHODS
We searched PubMed, Cochrane Central Register of Controlled Trials, EMBASE, PsycINFO, CINAHL, TRIP, and JBI Ovid databases and conducted a grey literature search. Articles discussing methods for deprescribing benzodiazepines or Z-drugs in community-dwelling adults were selected.
RESULTS
Following removal of duplicates, 2797 articles were reviewed for eligibility. Of these, 367 were retrieved for full-text assessment and 139 were subsequently included for review. Seventy-four (53%) articles were original research, predominantly randomized controlled trials (n = 52 [37%]), whereas 58 (42%) were narrative reviews and seven (5%) were guidelines. Amongst original studies, pharmacologic strategies were the most commonly studied intervention (n = 42 [57%]). Additional deprescribing strategies included psychological therapies (n = 10 [14%]), mixed interventions (n = 12 [16%]), and others (n = 10 [14%]). Behaviour change interventions were commonly combined and included enablement (n = 56 [76%]), education (n = 36 [47%]), and training (n = 29 [39%]). Gradual dose reduction was frequently a component of studies, reviews, and guidelines, but methods varied widely.
CONCLUSIONS
Approaches proposed for deprescribing benzodiazepines and Z-drugs are numerous and heterogeneous. Current research in this area using methods such as randomized trials and meta-analyses may too narrowly encompass potential strategies available to target this phenomenon. Realist synthesis methods would be well suited to understand the mechanisms by which deprescribing interventions work and why they fail.
Topics: Acetamides; Azabicyclo Compounds; Benzodiazepines; Deprescriptions; Humans; Piperazines; Pyridines; Pyrimidines; Zolpidem
PubMed: 26141716
DOI: 10.1186/s40360-015-0019-8 -
Journal of Clinical Sleep Medicine :... Mar 2023Patients with chronic insomnia may respond differently to therapeutic modalities. This study examined differences in response of individuals with 2 insomnia... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparison of the treatment effectiveness between lemborexant and zolpidem tartrate extended-release for insomnia disorder subtypes defined based on polysomnographic findings.
STUDY OBJECTIVES
Patients with chronic insomnia may respond differently to therapeutic modalities. This study examined differences in response of individuals with 2 insomnia phenotypes-short sleep duration (I-SSD; < 6 hours) and normal sleep duration (I-NSD; ≥ 6 hours) determined by polysomnography-to treatment with lemborexant and zolpidem tartrate extended-release 6.25 mg (zolpidem ER), compared with placebo.
METHODS
Study E2006-G000-304 (Study 304; SUNRISE-1; NCT02783729) was a global, randomized, double-blind, placebo, and active comparator-controlled, parallel-group study comparing lemborexant 5 and 10 mg in individuals aged ≥ 55 years with insomnia disorder. In this analysis, changes in subjective (self-reported) variables based on sleep diaries and objective variables based on polysomnographs were assessed after 1-month administration of study drugs. Data from participants with I-SSD and I-NSD were compared.
RESULTS
In the I-SSD subgroup, both lemborexant doses provided significant benefit for sleep-onset latency (SOL), total sleep time (TST), and wake after sleep onset (WASO) vs placebo; zolpidem ER also provided significant benefit for TST and WASO, but not SOL, on both measures vs placebo. In the I-NSD subgroup, lemborexant and zolpidem ER provided significant benefit for TST and WASO vs placebo objectively but not subjectively; both doses of lemborexant provided significant benefit for SOL vs placebo subjectively, but not objectively.
CONCLUSIONS
Both drugs, but lemborexant more consistently, showed subjective and objective benefits compared with placebo in participants with insomnia with objective short sleep duration. However, neither lemborexant nor zolpidem provided consistent benefits for participants with normal sleep duration on sleep-onset and sleep maintenance variables.
CLINICAL TRIAL REGISTRATION
Registry: ClinicalTrials.gov; Name: Study of the Efficacy and Safety of Lemborexant in Subjects 55 Years and Older With Insomnia Disorder (SUNRISE 1); URL: https://clinicaltrials.gov/ct2/show/record/NCT02783729; Identifier: NCT02783729.
CITATION
Inoue Y, Nishida M, Kubota N, et al. Comparison of the treatment effectiveness between lemborexant and zolpidem tartrate extended-release for insomnia disorder subtypes defined based on polysomnographic findings. . 2023;19(3):519-528.
Topics: Humans; Zolpidem; Sleep Initiation and Maintenance Disorders; Hypnotics and Sedatives; Treatment Outcome; Double-Blind Method
PubMed: 36472134
DOI: 10.5664/jcsm.10378 -
Journal of Clinical Sleep Medicine :... Dec 2011To describe zolpidem-associated complex behaviors, including both daytime automatisms and sleep-related parasomnias.
STUDY OBJECTIVES
To describe zolpidem-associated complex behaviors, including both daytime automatisms and sleep-related parasomnias.
METHODS
A case series of eight clinical patients and six legal defendants is presented. Patients presented to the author after an episode of confusion, amnesia, or somnambulism. Legal defendants were being prosecuted for driving under the influence, and the author reviewed the cases as expert witness for the defense. Potential predisposing factors including comorbidities, social situation, physician instruction, concomitant medications, and patterns of medication management were considered.
RESULTS
Patients and defendants exhibited abnormal behavior characterized by poor motor control and confusion. Although remaining apparently interactive with the environment, all reported amnesia for 3 to 5 hours. In some cases, the episodes began during daytime wakefulness because of accidental or purposeful ingestion of the zolpidem and are considered automatisms. Other cases began after ingestion of zolpidem at the time of going to bed and are considered parasomnias. Risk factors for both wake and sleep-related automatic complex behaviors include the concomitant ingestion of other sedating drugs, a higher dose of zolpidem, a history of parasomnia, ingestion at times other than bedtime or when sleep is unlikely, poor management of pill bottles, and living alone. In addition, similar size and shape of two medications contributed to accidental ingestion in at least one case.
CONCLUSIONS
Sleep driving and other complex behaviors can occur after zolpidem ingestion. Physicians should assess patients for potential risk factors and inquire about parasomnias. Serious legal and medical complications can occur as a result of these forms of automatic complex behaviors.
Topics: Adult; Aged; Automatism; Automobile Driving; Female; Follow-Up Studies; Headache; Humans; Hypnotics and Sedatives; Liability, Legal; Male; Mental Disorders; Middle Aged; Pyridines; Risk Assessment; Sampling Studies; Severity of Illness Index; Sleep Initiation and Maintenance Disorders; Somnambulism; Zolpidem
PubMed: 22171202
DOI: 10.5664/jcsm.1468 -
Journal of Family & Reproductive Health Sep 2020To evaluate the efficacy of Zolpidem and Nigella sativa compared to placebo in treatment of sleep disturbance in healthy postmenopausal women. Menopause is a period...
To evaluate the efficacy of Zolpidem and Nigella sativa compared to placebo in treatment of sleep disturbance in healthy postmenopausal women. Menopause is a period that diagnosed after 12 months of amenorrhea and is characterized by a group of symptoms that include irregular menses; vasomotor and urogenital symptoms. The effects of non-hormonal therapies are being widely researched on menopause symptoms. There has been no study to compare Zolpidem and Nigella sativa versus placebo. In this double-blind, placebo controlled trial, we compared the effect of Zolpidem with Nigella sativa and placebo in reducing sleep quality in 60 menopausal women. The prior and the later results were compared. We divided the patients into three groups after history taking and physical examination and filling the Pittsburgh questionnaire. Each group received their medication as the following order: Group A: Zolpidem, Group B: Nigella sativa, Group C: placebo. The first group received Zolpidem with the dose of 5 mg for 8 weeks. The second group received Nigella sativa with the dose of 600 mg for 8 weeks. The third group received placebo for 8 weeks. After two months, the Pittsburg questionnaire was filled again. In the nigella sativa group, we had not significant improvement in sleep quality (p =0.07), hot flashes (p =0.15), palpitation (p =0.56) and night sweets (p =0.08). In zolpidem group, we have seen lack of improvement of hot flashes (p =0.73), and palpitation (p =0.36), which are nonsignificant statistically according to p values, but in zolpidem group, we had significant improvement in sleep quality (p =0.01), and night sweats (p =0.049). It seems that zolpidem has some effect on improving the quality of sleep in postmenopausal women. zolpidem also is good for night sweats. Nigella sativa was not effective in vasomotor symptoms and sleep quality.
PubMed: 33603811
DOI: 10.18502/jfrh.v14i3.4672 -
Clinical Journal of the American... Dec 2020Zolpidem, a nonbenzodiazepine hypnotic, and trazodone, a sedating antidepressant, are the most common medications used to treat insomnia in the United States. Both drugs... (Comparative Study)
Comparative Study
BACKGROUND AND OBJECTIVES
Zolpidem, a nonbenzodiazepine hypnotic, and trazodone, a sedating antidepressant, are the most common medications used to treat insomnia in the United States. Both drugs have side effect profiles (., drowsiness, dizziness, and cognitive and motor impairment) that can heighten the risk of falls and fractures. Despite widespread zolpidem and trazodone use, little is known about the comparative safety of these medications in patients receiving hemodialysis, a vulnerable population with an exceedingly high fracture rate.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
Using data from the United States Renal Data System registry (2013-2016), we conducted a retrospective cohort study to investigate the association between the initiation of zolpidem versus trazodone therapy and the 30-day risk of hospitalized fall-related fractures among Medicare-enrolled patients receiving maintenance hemodialysis. We used an active comparator new-user design and estimated 30-day inverse probability of treatment-weighted hazard ratios and risk differences. We treated death as a competing event.
RESULTS
A total of 31,055 patients were included: 18,941 zolpidem initiators (61%) and 12,114 trazodone initiators (39%). During the 30-day follow-up period, 101 fall-related fractures occurred. Zolpidem versus trazodone initiation was associated with a higher risk of hospitalized fall-related fracture (weighted hazard ratio, 1.71; 95% confidence interval, 1.11 to 2.63; weighted risk difference, 0.17%; 95% confidence interval, 0.07% to 0.29%). This association was more pronounced among individuals prescribed higher zolpidem doses (hazard ratio, 1.85; 95% confidence interval, 1.10 to 3.01; and risk difference, 0.20%; 95% confidence interval, 0.04% to 0.38% for higher-dose zolpidem versus trazodone; and hazard ratio, 1.60; 95% confidence interval, 1.01 to 2.55 and risk difference, 0.14%; 95% confidence interval, 0.03% to 0.27% for lower-dose zolpidem versus trazodone). Sensitivity analyses using longer follow-up durations yielded similar results.
CONCLUSIONS
Among individuals receiving maintenance hemodialysis, zolpidem initiators had a higher risk of hospitalized fall-related fracture compared with trazodone initiators.
PODCAST
This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_12_18_CJN10070620_final.mp3.
Topics: Accidental Falls; Aged; Cognitive Dysfunction; Dizziness; Drug Prescriptions; Female; Fractures, Bone; Hospitalization; Humans; Male; Medicare; Middle Aged; Registries; Renal Dialysis; Renal Insufficiency, Chronic; Retrospective Studies; Sleep Aids, Pharmaceutical; Sleep Initiation and Maintenance Disorders; Trazodone; United States; Zolpidem
PubMed: 33355192
DOI: 10.2215/CJN.10070620 -
Sleep & Breathing = Schlaf & Atmung Mar 2023Arousals may contribute to the pathogenesis of sleep-disordered breathing (SDB) and central sleep apnea (CSA). We aimed to determine the effect of the nonbenzodiazepine... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Arousals may contribute to the pathogenesis of sleep-disordered breathing (SDB) and central sleep apnea (CSA). We aimed to determine the effect of the nonbenzodiazepine hypnotic zolpidem on the frequency of respiratory-related arousals and central apnea in patients with moderate-to-severe SDB. We hypothesized that zolpidem decreases the severity of SDB by decreasing the frequency of respiratory-related arousals.
METHODS
Patients with apnea-hypopnea index ≥ 15 events/hour and central apnea-hypopnea index ≥ 5 events/hour underwent a sleep study on zolpidem 5 mg and a sleep study with no medication in a randomized order. The respiratory arousal index was compared between the two studies using a randomized crossover design. Sleep, respiratory, and physiologic parameters, including the CO reserve and the respiratory arousal threshold, were also compared.
RESULTS
Eleven participants completed the study. Compared to no treatment, zolpidem reduced the respiratory arousal index (39.7 ± 7.7 vs. 23.3 ± 4.4 events/h, P = 0.031). Zolpidem also lowered the total apnea-hypopnea index (55.6 ± 8.5 vs. 41.3 ± 7.5 events/hour, P = 0.033) but did not affect other clinical and physiologic parameters. Compared to control, zolpidem did not widen CO reserve (- 0.44 ± 1.47 vs. - 0.63 ± 0.86 mmHg, P = 0.81). The respiratory arousal threshold did not show a significant change on zolpidem compared to control (- 8.72 ± 2.1 vs. - 8.25 ± 2.81 cmHO, P = 0.41).
CONCLUSION
Nocturnal arousals and overall SDB severity were reduced with a single dose of zolpidem in patients with moderate-to-severe sleep-disordered breathing with increased susceptibility for central apnea. Zolpidem did not widen the CO reserve or increase the arousal threshold.
TRIAL REGISTRATION
Clinicaltrials.gov. Sleep and Breathing in the General Population - Chemical Stimuli (NCT04720547).
Topics: Humans; Arousal; Carbon Dioxide; Sleep Apnea Syndromes; Sleep Apnea, Central; Zolpidem; Cross-Over Studies
PubMed: 35286569
DOI: 10.1007/s11325-022-02593-3 -
Journal of Clinical PsychopharmacologyLemborexant (LEM) is a dual orexin receptor antagonist approved for the treatment of insomnia in adults in multiple countries including the the United States, Japan,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Lemborexant (LEM) is a dual orexin receptor antagonist approved for the treatment of insomnia in adults in multiple countries including the the United States, Japan, Canada, Australia and several Asian countries.
PROCEDURES
This was a randomized, single-dose, single-center, double-blind, active-control, 6-way crossover study to evaluate LEM abuse potential. The study assessed oral doses of LEM 10 mg (LEM10), 20 mg (LEM20), and 30 mg (LEM30) compared with placebo (PBO), zolpidem (ZOL) immediate release 30 mg, and suvorexant (SUV) 40 mg. Subjects were healthy, nondependent, recreational sedative users able to discriminate/like the effects of both SUV and ZOL from PBO during a qualification phase.
RESULTS
Abuse potential endpoints were analyzed in qualified subjects who received and completed all treatments (n = 32). On the "at this moment" drug-liking visual analog scale (VAS), mean maximum (peak) effect (primary endpoint) values were 78.4, 80.5, and 83.6 for LEM10, LEM20, and LEM30, respectively, which were all significantly greater than PBO (57.8; all P > 0.05) but not different from SUV (76.1) or ZOL (78.3). Similarly, for secondary endpoints overall drug-liking VAS and take-drug-again VAS, mean maximum (peak) effect values for all LEM doses were significantly greater than PBO ( P > 0.05) but not different compared with ZOL or SUV.
CONCLUSIONS
For all doses, LEM demonstrated abuse potential versus PBO and appeared to have a similar abuse potential profile to ZOL and SUV in this study population. Lemborexant was well tolerated. Lemborexant has been placed in Schedule IV, the same drug schedule as ZOL and SUV.
Topics: Adult; Azepines; Cross-Over Studies; Double-Blind Method; Humans; Hypnotics and Sedatives; Orexin Receptor Antagonists; Pyridines; Pyrimidines; Triazoles; Zolpidem
PubMed: 35749758
DOI: 10.1097/JCP.0000000000001561 -
Annales de Biologie Clinique 2009The authors report an suicide attempt by a 43 years old woman treated by Previscan, Effexor, Rivotril, and Stilnox for phlebitis anteriority and anxious-depressive...
The authors report an suicide attempt by a 43 years old woman treated by Previscan, Effexor, Rivotril, and Stilnox for phlebitis anteriority and anxious-depressive disorders. On arrival to the emergency unit, the medical status and the patient history required a cardiovascular reanimation and gastric washing. The haemostasis analysis demonstrates an anticoagulant overdose and the prescription of vitamine K1 and PPSB was necessary. Later, the multidrug poisoning was demonstrated thanks to blood, urinary and gastric fluid high performance liquid chromatography toxicological analyses. This case report points out that biological and toxicological analyses are complementary. The first ones are useful to determine the emergency symptomatic cares, and to check the drugs' efficiency. The second ones, although longer, are necessary to identify with certainty incriminated drugs.
Topics: Anti-Anxiety Agents; Anticoagulants; Antidepressive Agents; Antipsychotic Agents; Clonazepam; Cyclohexanols; Electrocardiography; Female; Humans; Hypnotics and Sedatives; Middle Aged; Phenindione; Phlebitis; Pyridines; Suicide, Attempted; Venlafaxine Hydrochloride; Zolpidem
PubMed: 19297297
DOI: 10.1684/abc.2009.0316 -
The Journal of Physiology Oct 2020A decreased respiratory arousal threshold is one of the main contributors to obstructive sleep apnoea (OSA) pathogenesis. Several recent studies have sought to find a... (Randomized Controlled Trial)
Randomized Controlled Trial
KEY POINTS
A decreased respiratory arousal threshold is one of the main contributors to obstructive sleep apnoea (OSA) pathogenesis. Several recent studies have sought to find a drug capable of increasing the respiratory arousal threshold without impairing pharyngeal muscle activity to reduce OSA severity, with variable success. Here we show that zolpidem increases the respiratory arousal threshold by ∼15%, an effect size which was insufficient to systematically decrease OSA severity as measured by the apnoea-hypopnoea index. Unlike recent physiological findings that showed paradoxical increases in pharyngeal muscle responsiveness during transient manipulations of airway pressure, zolpidem did not alter pharyngeal muscle responsiveness during natural sleep. It did, however, increase sleep efficiency without changing apnoea length, oxygen desaturation, next-day perceived sleepiness and alertness. These novel findings indicate that zolpidem was well tolerated and effective in promoting sleep in people with OSA, which may be therapeutically useful for people with OSA and comorbid insomnia.
ABSTRACT
A recent physiology study performed using continuous positive airway pressure (CPAP) manipulations indicated that the hypnotic zolpidem increases the arousal threshold and genioglossus responsiveness in people with and without obstructive sleep apnoea (OSA). Thus, zolpidem may stabilise breathing and reduce OSA severity without CPAP. Accordingly, we sought to determine the effects of zolpidem on OSA severity, upper airway physiology and next-day sleepiness and alertness. Nineteen people with OSA with low-to-moderate arousal threshold received 10 mg zolpidem or placebo according to a double-blind, randomised, cross-over design. Participants completed two overnight in-laboratory polysomnographies (1-week washout), with an epiglottic catheter, intramuscular genioglossus electromyography, nasal mask and pneumotachograph to measure OSA severity, arousal threshold and upper airway muscle responsiveness. Next-morning sleepiness and alertness were also assessed. Zolpidem did not change the apnoea-hypopnoea index versus placebo (40.6 ± 12.3 vs. 40.3 ± 16.4 events/h (means ± SD), p = 0.938) or nadir oxyhaemoglobin saturation (79.6 ± 6.6 vs. 79.7 ± 7.4%, p = 0.932), but was well tolerated. Zolpidem increased sleep efficiency by 9 ± 14% (83 ± 11 vs. 73 ± 17%, p = 0.010). Arousal threshold increased by 15 ± 5% with zolpidem throughout all sleep stages (p = 0.010), whereas genioglossus muscle responsiveness did not change. Next-morning sleepiness and alertness were not different between nights. In summary, a single night of 10 mg zolpidem is well tolerated and does not cause next-day impairment in alertness or sleepiness, or overnight hypoxaemia in OSA. However, despite increases in arousal threshold without any change in pharyngeal muscle responsiveness, zolpidem does not alter OSA severity. It does, however, increase sleep efficiency by ∼10%, which may be beneficial in people with OSA and insomnia.
Topics: Arousal; Continuous Positive Airway Pressure; Humans; Pharyngeal Muscles; Sleep; Zolpidem
PubMed: 32864734
DOI: 10.1113/JP280173