Hypnotics in Insomnia: The Experience of Zolpidem

PurposeOne of the most commonly prescribed medications to treat insomnia is zolpidem, a nonbenzodiazepine compound that is available as an immediate-release oral tablet formulation, an extended-release oral formulation, an oral spray formulation, and as sublingual formulations. The purpose of this review was to summarize the data currently available on the efficacy and safety of zolpidem in the treatment of insomnia among adults.MethodsPublished studies on the use of zolpidem in the treatment of insomnia were identified by using combinations of relevant search terms in PubMed and Google Scholar. Studies were included if they were placebo- or active comparator–controlled studies, with the exception of trials on the long-term use of zolpidem. Studies were limited to those conducted in adults. Studies were not included if the patient population was small, if the study was not designed or powered to assess the efficacy or safety of zolpidem, if insomniac patients had a medical condition in addition to insomnia (with the exception of comorbid depression or anxiety for studies on comorbid insomnia), or if zolpidem was given concomitantly with any other therapy (with the exception of selective serotonin reuptake inhibitors for studies on comorbid insomnia).FindingsTwenty-five studies designed to evaluate the efficacy of zolpidem in insomnia and 51 studies reporting the safety of zolpidem in insomnia were included in this review.ImplicationsThe studies discussed in this review report the efficacy and safety of zolpidem in both young adults and the elderly. It can be used for either bedtime or middle-of-the-night administration, over the short or long term, with minimal risk of withdrawal or abuse. The use of zolpidem is associated with rebound insomnia, complex sleep-related behaviors, and next-day residual effects (after middle-of-the-night dosing) on driving ability, memory, and psychomotor performance.     

Is There Any Objective Improvement of Nocturia by Combination Treatment of Zolpidem and Alpha‐Blocker Therapy for Unresponsive to Alpha‐Blocker Monotherapy in Men with Lower Urinary Tract Symptoms?

Objectives: The aim of the present study was to determine whether administration of zolpidem, a nonbenzodiazepine sedative‐hypnotic agent, at night would improve the nocturia unresponsive to alpha‐blocker monotherapy in men with lower urinary tract symptoms (LUTS). Methods: This was a prospective observational study comprised of 39 men aged 50 years and older. The study inclusion criteria were age more than 50 years, and nocturia twice or more per night after taking alpha‐blockers for more than 8 weeks. A total of 39 patients met the criteria and constituted the study cohort. Pittsburgh Sleep Quality Index (PSQI), International Prostate Symptom Score (IPSS), frequency volume chart (FVCs) and uroflowmetry were recorded. Patients were given 10 mg alfuzosin and 10 mg zolpidem once at night for the 8 weeks. Results: There were no serious side‐effects in any patient. Nocturia decreased from a baseline (3.1 ± 0.1) to 8 weeks (1.6 ± 0.2) (P = 0.001). After treatment, global PSQI scores and severe sleep disorders improved. Storage and voiding symptoms including total IPSS scores and quality of life index improved. Nocturnal urine volume and functional bladder capacity improved. Maximum flow rate, voided volume increased and residual urine volume decreased. Conclusion: Combined zolpidem and alpha‐blocker therapy resulted in a subjective and objective reduction in nocturia episodes when given to men with nocturia unresponsive to alpha‐blocker monotherapy.     

Differential Roles of GABAA Receptor Subtypes in Benzodiazepine-Induced Enhancement of Brain-Stimulation Reward

Benzodiazepines such as diazepam are widely prescribed as anxiolytics and sleep aids. Continued use of benzodiazepines, however, can lead to addiction in vulnerable individuals. Here, we investigate the neural mechanisms of the behavioral effects of benzodiazepines using the intracranial self-stimulation (ICSS) test, a procedure with which the reward-enhancing effects of these drugs can be measured. Benzodiazepines bind nonselectively to several different GABA_A receptor subtypes. To elucidate the α subunit(s) responsible for the reward-enhancing effects of benzodiazepines, we examined mice carrying a histidine-to-arginine point mutation in the α1, α2, or α3 subunit, which renders the targeted subunit nonresponsive to diazepam, other benzodiazepines and zolpidem. In wild-type and α1-point-mutated mice, diazepam caused a dose-dependent reduction in ICSS thresholds (reflecting a reward-enhancing effect) that is comparable to the reduction observed following cocaine administration. This effect was abolished in α2- and α3-point-mutant mice, suggesting that these subunits are necessary for the reward-enhancing action of diazepam. α2 Subunits appear to be particularly important, since diazepam increased ICSS thresholds (reflecting an aversive-like effect) in α2-point-mutant animals. Zolpidem, an α1-preferring benzodiazepine-site agonist, had no reward-enhancing effects in any genotype. Our findings implicate α2 and α3 subunit containing GABA_A receptors as key mediators of the reward-related effects of benzodiazepines. This finding has important implications for the development of new medications that retain the therapeutic effects of benzodiazepines but lack abuse liability.     

Age Cohort Differences in the Nonmedical Use of Prescription Zolpidem: Findings from a Nationally Representative Sample

Background

Recent warnings from the FDA have highlighted the potential risks associated with zolpidem use. These risks may be especially acute in nonmedical users of zolpidem, but little work has examined the characteristics of such nonmedical users. This study aims to investigate the correlates of nonmedical use of zolpidem (NUPZ) across the lifespan and potential age cohort-based differences in NUPZ correlates.

Methods

Data from the 2009–2011 versions of the National Survey on Drug Use and Health were used (n = 174,667). Analyses used weighted design-based logistic regressions to examine a set of substance use and mental health correlates within five separate age cohorts and differences in correlate magnitude between these cohorts.

Results

Most examined substance use and mental health variables were significant correlates of NUPZ, though odds ratio (OR) magnitude tended to drop with increasing age. Age-based differences were most apparent for substance use correlates of both lifetime and past year NUPZ, with significantly higher ORs in adolescent nonmedical users. Mental health variables operated more consistently across age, with OR magnitudes that were generally in the same range, regardless of age cohort.

Conclusions

Age-based differences in NUPZ correlates suggest motives may change for NUPZ through the lifespan, though this cannot be established with the cross-sectional data used in this work. Clinicians screening for NUPZ should emphasize such screening in high-risk individuals with substance use and/or mental health problems.     

Effectiveness and safety profiling of zolpidem and acupressure in CKD associated pruritus: An interventional study

Background:Chronic kidney disease (CKD)-associated pruritus (CKD-aP) contributes to poor quality of life, including reduced sleep quality and poor sleep quality is a source of patient stress and is linked to lower health-related quality of life. This study aimed to investigate the effectiveness of zolpidem 10 mg and acupressure therapy on foot acupoints to improve the sleep quality and overall quality of life among hemodialysis patients suffering from CKD-aP.Method:A multicenter, prospective, randomized, parallel-design, open label interventional study to estimate the effectiveness of zolpidem (10 mg) oral tablets versus acupressure on sleep quality and quality of life in patients with CKD-aP on hemodialysis. A total of 58 hemodialysis patients having sleep disturbance due to CKD-aP completed the entire 8-week follow-up. The patients were divided into a control (acupressure) group of 28 patients and an intervention (zolpidem) group of 30 patients.Results:A total of 58 patients having CKD-aP and sleep disturbance were recruited. In the control group there was a reduction in the PSQI score with a mean ± SD from 12.28 ± 3.59 to 9.25 ± 3.99, while in the intervention group the reduction in PSQI score with a mean ± SD was from 14.73 ± 4.14 to 10.03 ± 4.04 from baseline to endpoint. However, the EQ5D index score and EQ-visual analogue scale (VAS) at baseline for the control group with a mean ± SD was 0.49 ± 0.30 and 50.17 ± 8.65, respectively, while for the intervention group the values were 0.62 ± 0.26 and 47.17 ± 5.82, respectively. The mean EQ5D index score in the control group improved from 0.49 ± 0.30 to 0.53 ± 0.30, but in the intervention group there was no statistical improvement in mean EQ5D index score from 0.62 ± 0.26 to 0.62 ± 0.27 from baseline to week 8. The EQ 5D improved in both groups and the EQ-VAS score was 2.67 points higher at week 8 as compared to baseline in the control group, while in the intervention group the score was 3.33 points higher at week 8 as compared to baseline. Comparing with baseline, the PSQI scores were significantly reduced after week 4 and week 8 (P =  < .001). Furthermore, at the end of the study, the PSQI scores were significantly higher in the control as compared to the intervention group (P = .012).Conclusion:An improvement in sleep quality and quality of life among CKD-aP patients on hemodialysis has been observed in both the control and intervention groups. Zolpidem and acupressure safety profiling showed no severe adverse effect other that drowsiness, nausea and daytime sleeping already reported in literature of zolpidem.     

Clinically Significant Response to Zolpidem in Disorders of Consciousness Secondary to Anti-N-Methyl-d-Aspartate Receptor Encephalitis in a Teenager: A Case Report

BackgroundAnti-N-methyl-d-aspartate receptor encephalitis has been associated with a prolonged neuropsychiatric phase that may last for months to years.PatientWe report the case of a 16-year-old girl who was diagnosed with anti-N-methyl-d-aspartate receptor encephalitis resulting from left ovarian mature teratoma 2 weeks after presentation with psychosis. Following tumor removal and immunotherapy, recovery from a minimally conscious state was accelerated significantly by zolpidem that was used for her sleep disturbance. Our patient was discharged home 8 weeks after admission with marked improvement in her neurological function. Zolpidem has been reported to improve arousal in disorders of consciousness but there are no previous reports of its benefit among patients with anti-N-methyl-d-aspartate receptor encephalitis.ConclusionZolpidem would be a reasonable consideration as an adjunctive treatment in anti-N-methyl-d-aspartate receptor encephalitis after tumor removal and immunotherapy to accelerate recovery and rehabilitation.     

Sleeping through the night: are extended-release formulations the answer?

PURPOSE: To provide an overview of insomnia, including identification and current treatments, as well as review the efficacy and safety of extended-release sleep medication. DATA SOURCES: Published clinical research and review articles, DSM-IV criteria, and clinical trials. CONCLUSIONS: Insomnia is a highly prevalent and debilitating sleep disorder, which may present with one or more of the following symptoms: difficulty initiating sleep, difficulty maintaining sleep, or waking too early without being able to return to sleep. Difficulty maintaining sleep throughout the night is the most common symptom of insomnia. The recently approved nonbenzodiazepine hypnotic, zolpidem extended-release, can be taken as long as medically necessary to improve sleep-onset and reduce sleep-maintenance difficulties in insomnia patients, without negatively affecting next-day functioning. IMPLICATIONS FOR PRACTICE: Insomnia continues to be an underdiagnosed and undertreated disorder. The nurse practitioner, through routine inquiry about patient sleep habits and consideration of the appropriate treatment of insomnia, can help restore the quality of life of patients experiencing the negative consequences of insomnia.     

HPLC法测定酒石酸唑吡坦口腔崩解片的含量

目的建立酒石酸唑吡坦口腔崩解片含量测定的反相高效液相色谱法。方法色谱柱为AlltimaC8柱(250mm×4.6mm,5μm),流动相为甲醇-0.1mol·L-1醋酸铵溶液(60∶40);流速为1.0mL·min-1;检测波长310nm。结果线性范围为20～200μg·mL-1,r=0.9999,平均回收率为99.92%,RSD=0.32%(n=15)。结论本法灵敏度高,重现性好,结果准确、可靠。