唑吡坦治疗失眠症双盲研究

目的：比较国产唑吡坦片和进口唑吡坦片治疗失眠症的疗效和不良反应。方法：对32例失眠症患者随机分为两组,分别服用国产或进口唑吡坦。采用睡眠障碍量表（SDRS）、汉密尔顿焦虑量表（HAMA）、临床总体印象量表（CGI）和副反应量表（TESS）评定疗效和不良反应。结果：SDRS评定国产唑吡坦组减分率为49．7％,与进口唑吡坦组49．8％相近,主要不良反应为头痛、口干、便秘和出汗等,病人均能耐受。结论：国产唑吡坦治疗失眠症的疗效和进口唑吡坦相当。     

Brain function in the vegetative state

Positron emission tomography (PET) techniques represent a useful tool to better understand the residual brain function in vegetative state patients. It has been shown that overall cerebral metabolic rates for glucose are massively reduced in this condition. However, the recovery of consciousness from vegetative state is not always associated with substantial changes in global metabolism. This finding led us to hypothesize that some vegetative patients are unconscious not just because of a global loss of neuronal function, but rather due to an altered activity in some critical brain regions and to the abolished functional connections between them. We used voxel-based Statistical Parametric Mapping (SPM) approaches to characterize the functional neuroanatomy of the vegetative state. The most dysfunctional brain regions were bilateral frontal and parieto-temporal associative cortices. Despite the metabolic impairment, external stimulation still induced a significant neuronal activation (i.e., change in blood flow) in vegetative patients as shown by both auditory click stimuli and noxious somatosensory stimuli. However, this activation was limited to primary cortices and dissociated from higher-order associative cortices, thought to be necessary for conscious perception. Finally, we demonstrated that vegetative patients have impaired functional connections between distant cortical areas and between the thalami and the cortex and, more importantly, that recovery of consciousness is paralleled by a restoration of this cortico-thalamo-cortical interaction.     

Amnestic sleep-related eating disorder associated with zolpidem

OBJECTIVE: To describe the association of amnestic nocturnal eating behavior with use of zolpidem for insomnia. BACKGROUND: Sleep-related eating disorder is increasingly recognized in relationship to other diagnosable sleep disorders. Many of these disorders, like restless legs syndrome (RLS), give rise to complaints of insomnia. Zolpidem is the most commonly prescribed drug for insomnia complaints, and although it has sometimes been associated with side effects of transient amnesia and sleep walking, an association with sleep-related eating has not been previously emphasized. METHODS: Consecutive case series of five patients who were using zolpidem and evaluated with nocturnal eating behaviors. RESULTS: We evaluated five patients over 11 months with problematic amnestic nocturnal eating associated with zolpidem used for complaints of insomnia. All five patients had RLS, three had obstructive sleep apnea syndrome, two had sleep walking, and one had psychophysiologic insomnia. With discontinuation of zolpidem and effective treatment of their sleep disorders, nocturnal eating resolved. CONCLUSIONS: Zolpidem, at least in patients with underlying sleep disorders that cause frequent arousals, may cause or augment sleep-related eating behavior. This report demonstrates the importance of arriving at a specific diagnosis for insomnia complaints, and alerts the sleep practitioner to this unusual side effect of zolpidem.     

唑吡坦对脑损伤植物状态患者促醒疗效的观察

目的 观察非常规促醒药物唑吡坦对脑损伤昏迷植物状态患者的促醒作用,分析该作用是否存在干预时间相关性. 方法 采用单光子发射型计算机体层摄影技术观察7例服用唑吡坦的持续性植物状态患者服药0.5 h前后及1周后99Tcm-双半光乙酯(ECD)脑灌注显像.做可视化分析;应用脑状态监测仪(CSM)进行检测,对比用药前后脑状态指数、肌电指数、爆发抑制指数的变化;观察患者临床指标变化,包括语言功能、肢体运动功能、肌张力、睡眠质量等的变化. 结果 (1)患者服药后脑状态指数、肌电指数均高于服药前爆发抑制指数低于用药前,差异均有统计学意义(P<0.05).(2)服药后7例患者脑损害区血流较服药前明显增加.(3)7例患者中3例成功促醒,表现为服药后0.5 h能与家人及医生进行简单的交流,用药后第2天便能做简单的数学运算,下肢可遵嘱做屈曲运动.其中1例原有的肢体震颤及扭转痉挛明显缓解:余4例肌张力及睡眠质量改善. 结论 唑吡坦能恢复部分脑损害持续性植物状态患者的脑功能,脑功能的改善与服药时间长短无关,脑功能的改善是"一步到位"而非"逐步改善".     

Non-benzodiazepines for the treatment of insomnia

Benzodiazepine hypnotics, the mainstay of pharmacological treatment for insomnia, have been associated with altered sleep architecture, psychomotor and memory impairment, rebound insomnia, withdrawal effects, tolerance, dependence, abuse potential and respiratory depression. Non-benzodiazepines, such as zolpidem, zopiclone and zaleplon, demonstrate hypnotic efficacy similar to that of benzodiazepines along with excellent safety profiles. Non-benzodiazepines generally cause less disruption of normal sleep architecture than benzodiazepines. Psychomotor and memory impairment may be less problematic with non-benzodiazepines, especially when compared to longer-acting benzodiazepines. Rebound insomnia and withdrawal symptoms occur infrequently upon discontinuation of non-benzodiazepines and may be less common and milder than those seen upon discontinuation of some benzodiazepines. For the long-term treatment of insomnia, which is generally not recommended, zolpidem and zopiclone are particularly good options because they do not develop tolerance rapidly and have a low abuse potential. Limited data indicate that zaleplon has low tolerance and abuse potential, although further experience is needed to determine its long-term efficacy and safety profile. Since non-benzodiazepines produce minimal respiratory depression, they may be safer than benzodiazepines in patients with respiratory disorders. The choice of which hypnotic to use should be based on the patient's primary sleep complaint, health history, adverse effects and cost.     

Induced arousal following zolpidem treatment in a vegetative state after brain injury in 7 cases Analysis using visual single photon emission computerized tomography and digitized cerebral state monitor

BACKGROUND: Several studies have reported the use of zolpidem for induced arousal after permanent vegetative states. However, changes in brain function and EMG after zolpidem treatment requires further investigation. OBJECTIVE: To investigate the effect of zolpidem, an unconventional drug, on inducing arousal in patients in a permanent vegetative state after brain injury using visual single photon emission computerized tomography and digitized cerebral state monitor. DESIGN: A self-controlled observation. SETTING: Shenzhen People's Hospital.PARTICIPANTS: Seven patients in a permanent vegetative state were selected from the Department of Neurosurgery, Shenzhen People's Hospital from March 2005 to May 2007. The group included 5 males and 2 females, 24–55 years of age, with a mean age of 38.5 years. All seven patients had been in a permanent vegetative statement for at least six months. The patient group included three comatose patients, who had sustained injuries to the cerebral cortex, basal ganglia, or thalamus in motor vehicle accidents, and four patients, who had suffered primary/secondary brain stem injury. Informed consents were obtained from the patients’ relatives. METHODS: The patients brains were imaged by 99Tcm ECD single photon emission computerized tomography prior to treatment with zolpidem [Sanofi Winthrop Industrie, France, code number approved by the State Food & Drug Administration (SFDA) J20040033, specification 10 mg per tablet. At 8:00 p.m., 10 mg zolpidem was dissolved with distilled water and administered through a nasogastric tube at 1 hour before and after treatment and 1 week following treatment, respectively. Visual analysis of cerebral perfusion changes in the injured brain regions before and after treatment was performed. Simultaneously, three monitoring parameters were obtained though a cerebral state monitor, which included cerebral state index, electromyographic index, and burst suppression index. MAIN OUTCOME MEASURES: Comparison of the three brain function indices, cerebral perfusion in the areas of brain injury, and clinical indices before and after treatment. RESULTS: All seven patients were included in the final analysis. ① Following treatment, the parameters of cerebral state index and electromyographic index were significantly higher than before treatment (P < 0.05). The burst suppression index was significantly lower than before treatment (P < 0.05). ② Cerebral perfusion in areas of brain injury improved significantly in all subjects compared to before treatment. CONCLUSION: The findings of visual single photon emission computerized tomography and digitized cerebral state monitor reveal that Zolpidem appears to be an effective treatment for restoring brain function to certain patients in a permanent vegetative state.     

Central nervous system side effects associated with zolpidem treatment

Zolpidem is one of the newer medications developed for the treatment of insomnia. It is an imidazopyridine agent that is an alternative to the typical sedative-hypnotic agents. Zolpidem use is gaining favor because of its efficacy and its side effect profile, which is milder and less problematic than that of the benzodiazepines and barbiturates used to treat insomnia. Still, side effects are not uncommon with zolpidem use. We report a series of cases in which the patients developed delirium, nightmares and hallucinations during treatment with zolpidem. We will review its pharmacology, discuss previous reports of central nervous system side effects, examine the impact of drug interactions with concurrent use of antidepressants, examine gender differences in susceptibility to side effects, and explore the significance of protein binding in producing side effects.     

Anterior cingulate activity and the self in disorders of consciousness

Objectives: The aim of this study was to investigate the relationship between medial cortical activation and the presence of self and consciousness in healthy subjects and patients with vegetative state and minimally conscious state using functional magnetic resonance imaging (fMRI). Experiment design: We first conducted two fMRI experiments in healthy subjects to identify brain regions specifically associated with self‐perception through the use of different auditory stimuli that had different grades of self‐relatedness. We then applied these regions as functional localizers to examine the relationship between neural activity changes during self‐relatedness and consciousness level in the patients with disorders of consciousness (DOC). Principal observations: We demonstrated recruitment of various anterior medial cortical regions including the anterior cingulate cortex (ACC) in healthy subjects during auditory perception of self‐related stimuli. We further showed that patients with DOC showed signal changes in the ACC during auditory perception of self‐related stimuli. Finally, it was shown that these signal changes correlate with the level of consciousness in the patients with DOC. Conclusion: The degree of consciousness in patients with DOC was correlated with neural activity in the ACC induced by self‐related stimuli. Our results not only shed light on the pathophysiology of DOC, but may also suggest a useful neural, and thus diagnostic, marker of the dysfunction of consciousness in vegetative patients. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Exploring impaired consciousness: the MRI approach

PURPOSE OF REVIEW: To summarize the application of advanced MRI sequences such as magnetic resonance spectroscopy, diffusion tensor imaging and functional MRI for the evaluation of patients with altered consciousness. RECENT FINDINGS: Magnetic resonance spectroscopy, volumetry and diffusion tensor imaging have shown promising results in the evaluation of traumatic or anoxo-ischaemic brain lesions and can detect damage of the brainstem, basal ganglia and white matter tracts not visible on conventional sequences. A diffusion tensor imaging study has raised the possibility of detecting ongoing axonal regrowth many years after the initial injury in minimally conscious patients. Functional MRI studies have shown that a high level of brain activities, such as recognizing one's own name or imagining playing tennis, can be preserved in vegetative patients. SUMMARY: The development of quantitative imaging could lead to a more objective evaluation of the extent of destruction or preservation of critical brain areas at the acute phase of brain injury, which could be integrated in multi-parametric decisional strategies for these patients. Functional imaging could help define borders between the various levels of altered consciousness and detect the presence of cryptic residual functions in vegetative or minimally conscious patients. This approach could eventually help determine the neurological outcome and make individual blueprints of the preserved brain activities in severely brain injured patients.     

Dependence on zolpidem: a case report.

We report the case of a patient with a history of zolpidem dependence. The patient, after a stressful life event, started using zolpidem. She rapidly developed tolerance and dependence, taking 50-100 mg, and sometimes up to 300 mg, of zolpidem daily. Also, our patient suffered episodes of altered consciousness, accompanied by visual hallucinations.     

Efficacy and safety of Zolpidem in the treatment of insomnia disorder for one month: a meta-analysis of a randomized controlled trial

SubjectA meta-analysis of a randomized placebo-controlled trial was used to evaluate the effectiveness and safety of Zolpidem in the treatment of insomnia disorder for one month.MethodSearched from PubMed, EMBASE, MEDLINE, PsycINFO, Cochrane Central Register of Controlled Trials and web of science from inception to May 13, 2021. In addition, we also searched ClinicalTrials.gov trials register to obtain relevant research and related data. Include all randomized controlled trials that meet the criteria. The primary efficacy outcome were total sleep time and sleep latency. The secondary outcome was wake-time after sleep onset. And to evaluate the safety of Zolpidem in the treatment of insomnia.ResultsTotal of 6 randomized placebo-controlled trials involving 1068 patients with insomnia disorder were included in our study. Our analysis results showed that compared with placebo, zolpidem treatment for one month was more effective in increasing the total sleep time of patients with insomnia disorder, reducing sleep latency and improving sleep quality. There was no significant statistical difference between the two groups in the amount of change in the wake after sleep onset. Meanwhile, there was no significant statistical difference in adverse events between Zolpidem and placebo after one month of treatment.ConclusionOur meta-analysis showed that zolpidem is an effective and safe therapy option to treat insomnia disorder for one month. However, when using zolpidem to treat insomnia, its effect on sleep structure should be considered. In the future, large-scale clinical trials are needed to compare the effectiveness and safety of zolpidem in the treatment of insomnia from subjective and objective indicators combined with zolpidem on sleep structure.     

Sleep latency is shortened during 4 weeks of treatment with zaleplon, a novel nonbenzodiazepine hypnotic. Zaleplon Clinical Study Group.

BACKGROUND: Zaleplon is a short-acting pyrazolopyrimidine hypnotic with a rapid onset of action. This multicenter study compared the efficacy and safety of 3 doses of zaleplon with those of placebo in outpatients with DSM-III-R insomnia. Zolpidem, 10 mg, was used as an active comparator. METHOD: After a 7-night placebo (baseline) period, 615 adult patients were randomly assigned to receive, in double-blind fashion, I of 5 treatments (zaleplon, 5, 10, or 20 mg; zolpidem, 10 mg; or placebo) for 28 nights, followed by placebo treatment for 3 nights. Sleep latency, sleep maintenance, and sleep quality were determined from sleep questionnaires that patients completed each morning. The occurrence of rebound insomnia and withdrawal effects on discontinuation of treatment was also assessed. All levels of significance were p < or = .05. RESULTS: Median sleep latency was significantly lower with zaleplon, 10 and 20 mg, than with placebo during all 4 weeks of treatment and with zaleplon, 5 mg, for the first 3 weeks. Zaleplon, 20 mg, also significantly increased sleep duration compared with placebo in all but week 3 of the study. There was no evidence of rebound insomnia or withdrawal symptoms after discontinuation of 4 weeks of zaleplon treatment. Zolpidem, 10 mg, significantly decreased sleep latency, increased sleep duration, and improved sleep quality at most timepoints compared with placebo; however, after discontinuation of zolpidem treatment, the incidence of withdrawal symptoms was significantly greater than that with placebo and there was an indication of significant rebound insomnia for some patients in the zolpidem group compared with those in the placebo group. The frequency of adverse events in the active treatment groups did not differ significantly from that in the placebo group. CONCLUSION: Zaleplon is effective in the treatment of insomnia. In addition, zaleplon appears to provide a favorable safety profile, as indicated by the absence of rebound insomnia and withdrawal symptoms once treatment was discontinued.     

Benzodiazepine receptor binding of nonbenzodiazepines in vivo: Alpidem, zolpidem and zopiclone

Several classes of nonbenzodiazepine compounds, including imidazopyridines such as alpidem and zolpidem and cyclopyrrolones, e.g., zopiclone, have effects similar to benzodiazepines and may act at the benzodiazepine receptor in brain. We characterized the binding of these compounds to the benzodiazepine site in three brain regions using specific uptake of the high-affinity ligand [3H]Ro15-1788 (flumazenil). For alpidem, benzodiazepine binding was decreased in cortex and hippocampus with increasing drug dose. For zolpidem, receptor binding was reduced in cortex without a dose-response effect and no effect was observed on cerebellar binding. Zopiclone did not alter binding except for a decrease in binding at the lowest dose evaluated and an increase in binding above control at the highest dose. These data corroborate prior studies indicating that the imidazopyridines appear to act at the benzodiazepine receptor, but do not support receptor subtype selectivity of zolpidem. The limited effect of zopiclone except for increased binding at high doses is also consistent with prior studies suggesting that zopiclone acts at a site distinct from the benzodiazepine receptor.     

Efficacy and safety of zolpidem extended release in elderly primary insomnia patients.

OBJECTIVES: To evaluate the clinical efficacy and safety of zolpidem extended release for the treatment of primary insomnia in elderly patients. METHODS: A randomized, double-blind, placebo-controlled, parallel-group clinical trial was conducted. A total of 205 (117 women, 88 men; mean age 70.2 +/- 4.5 years) Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-defined primary insomnia patients were randomized to 3 weeks of nightly treatment with either zolpidem extended release 6.25 mg or placebo; 198 patients completed the study. RESULTS: Relative to placebo, zolpidem extended release 6.25 mg significantly decreased wake time after sleep onset during the first six hours of the night, as measured by polysomnogram (PSG). PSG latency to persistent sleep was reduced and PSG total sleep time was increased, both at nights 1/2 and 15/16. Patient self-report measures were significantly better with zolpidem extended-release 6.25 mg than with placebo throughout treatment. Some PSG measures indicated a worsening of sleep for a single night after abrupt discontinuation of zolpidem extended release. No next-morning residual effects were observed. The overall incidence and nature of adverse events was comparable between the two groups. CONCLUSIONS: Zolpidem extended release 6.25 mg improved both sleep maintenance and sleep induction in elderly primary insomnia patients during three weeks of administration.     

Abnormal auditory N400 in a case of zolpidem dependence, during a working memory test.

Zolpidem is a GABA (A) agonist, which is indicated for the short-term management of insomnia. Recent research provide evidence suggesting that zolpidem produces spatial working memory (WM) deficits and dependence; however, the underlying mechanisms of these effects are unknown. Since the auditory N400 component of event-related potentials (ERPS) is considered as an index of memory use of context processing, the present study focused on N400 waveform of ERPs elicited during a WM task in a case suffering from zolpidem dependence. The patterns of N400 waveform of this case were compared to the patterns obtained from healthy controls. This comparison revealed that zolpidem dependence is accompanied by reduced amplitudes located at posterior brain areas and diffuse prolongation of N400. These findings may indicate that zolpidem dependence manifests alterations with regard to the memory use of context processing, involving or affecting a wide-ranging network of the brain's structures.     

Zolpidem dependence and withdrawal seizure--report of two cases

Zolpidem is a non-benzodiazepine property which binds selectively to the ?1-GABAA receptors, and has been widely prescribed to patients suffering from insomnia. We report two cases of zolpidem dependence with withdrawal seizure in the Asian population. The first case is a 43-year-old woman who took zolpidem up to the dosage of 200 to 400 mg per night. The second case is a 35-year-old woman who even began to take zolpidem every 15 to 30 minutes to get euphoric and relaxed, and she gradually increased the dosage to 400 to 500mg per day. After abrupt discontinuation of zolpidem, both cases immediately developed anxiety, global insomnia, restlessness, and tonic seizure. The purpose of this case report is to suggest that clinicians should pay close attention to the potential of zolpidem tolerance, abuse and dependence. The possibility of withdrawal seizure cannot be excluded especially at high doses.     

A zolpidem and cocaine abuse case report

A case is presented of a 30-year-old man, prescribed zolpidem for insomnia arising from cocaine abuse, who sought to use this hypnotic to reduce his craving for cocaine. However, after taking cocaine and up to 300 mg/day zolpidem, he became euphoric and hyperactive. It is suggested that at high doses, zolpidem, like cocaine, has a stimulatory effect on the brain dopaminergic reward pathway. (Int J Psych Clin Pract 2002; 6: 217-219 )