Zolpidem-triggered atrial fibrillation in a patient with cardiomyopathy: a case report.

BACKGROUND: Zolpidem is a non-benzodiazepine hypnotic widely used to manage insomnia. Zolpidem-triggered atrial fibrillation (AF) in patients with cardiomyopathy has never been reported before. CASE PRESENTATION: A 40-year-old man with Duchenne muscular dystrophy-related cardiomyopathy attempted suicide and developed new-onset AF after zolpidem overdose. One year before admission, the patient visited our clinic due to chest discomfort and fatigue after daily walks for 1 month; both electrocardiography (ECG) and 24-hour Holter ECG results did not detect AF. After administration of cardiac medication (digoxin 0.125 mg/day, spironolactone 40 mg/day, furosemide 20 mg/day, bisoprolol 5 mg/day, sacubitril/valsartan 12/13 mg/day), he felt better. AF had never been observed before this admission via continuous monitoring during follow-up. Sixteen days before admission, the patient saw a sleep specialist and started zolpidem tartrate tablets (10 mg/day) due to insomnia for 6 months; ECG results revealed no significant change. The night before admission, the patient attempted suicide by overdosing on 40 mg of zolpidem after an argument, which resulted in severe lethargy. Upon admission, his ECG revealed new-onset AF, necessitating immediate cessation of zolpidem. Nine hours into admission, AF spontaneously terminated into normal sinus rhythm. Results from the ECG on the following days and the 24-hour Holter ECG at 1-month follow-up showed that AF was not detected. CONCLUSIONS: This study provides valuable clinical evidence indicating that zolpidem overdose may induce AF in patients with cardiomyopathy. It serves as a critical warning for clinicians when prescribing zolpidem, particularly for patients with existing heart conditions. Further large-scale studies are needed to validate this finding and to explore the mechanisms between zolpidem and AF.

The interactive walkway provides fit-for-purpose fall-risk biomarkers in the elderly: Comparison of zolpidem and suvorexant.

Dynamic balance assessments such as walking adaptability may yield a more realistic prediction of drug-induced falls compared with postural stability measurements, as falls often result from limited gait adjustments when walking. The Interactive Walkway (IWW) measures walking adaptability but sensitivity to medication effects is unknown. If proven sensitive and specific, IWW could serve as a biomarker for targeted fall-risk assessments in early clinical drug development. In this three-way crossover study, 18 healthy elderly (age: 65-80 years) subjects received 5 mg zolpidem, 10 mg suvorexant, or placebo in the morning. Assessments were performed pre-dose and approximately hourly until 9 h post-dose. IWW assessments included an 8-meter walking test, goal-directed stepping, obstacle-avoidance, and tandem-walking. Other pharmacodynamic measurements were the Timed-Up-and-Go (TUG) test at a comfortable and fast pace, adaptive tracking, and body sway. A decline in performance was observed for zolpidem compared with placebo for 3 h post-dose in IWW walking adaptability outcome measures, TUG, adaptive tracking, and body sway. For the IWW tasks, a decrease in walking speed (among others) was observed. IWW parameters were not affected by suvorexant compared with placebo at any timepoint. However, an increase of 9.8% (95%CI: 1.8%, 18.5%) in body sway was observed for suvorexant compared with placebo up to 3 h post-dose. The IWW successfully quantified drug effects of two hypnotic drugs and distinguished between zolpidem and suvorexant regarding their effects on walking. As a biomarker, the IWW demonstrated sensitivity in assessing dynamic balance and potential fall risk in early phase clinical drug development.

Treatment Failure and Long-Term Prescription Risk for Guideline-Recommended Hypnotics in Japan.

Importance: Although insomnia guidelines recommend the use of several individual hypnotics, the most useful hypnotic for treating insomnia in a clinical setting remains unclear. Objective: To determine which guideline-recommended hypnotics have lower risks of monotherapy failure and which hypnotics have a higher risk of long-term prescription for insomnia treatment. Design, Setting, and Participants: This retrospective observational cohort study used data from the Japan Medical Data Center Claims Database from April 1, 2005, to March 31, 2021. Participants included adults whose first prescribed pharmaceutical treatment for insomnia was guideline-recommended hypnotic monotherapy. Data were analyzed from December 24, 2022, to September 26, 2023. Exposures: Suvorexant, ramelteon, eszopiclone, zolpidem, and triazolam monotherapy. Main Outcomes and Measures: The primary outcome was monotherapy failure, defined as a change in hypnotic or having an additional hypnotic prescribed for insomnia within 6 months of the first prescription of a guideline-recommended hypnotic monotherapy. The secondary outcome was monotherapy discontinuation, defined as no prescription of any hypnotic for 2 consecutive months within 6 months after prescribing a guideline-recommended hypnotic in patients for whom monotherapy did not fail. Monotherapy failure and discontinuation were compared using Cox proportional hazards and logistic regression models, respectively. Results: The study included 239 568 adults (median age, 45 [IQR, 34-55] years; 50.2% women) whose first prescription for insomnia was guideline-recommended hypnotic monotherapy. During the 6-month follow-up period, 24 778 patients (10.3%) experienced failure of monotherapy with a guideline-recommended hypnotic. In comparison with eszopiclone, there were more cases of monotherapy failure for ramelteon (adjusted hazard ratio [AHR], 1.23 [95% CI], 1.17-1.30; P < .001), fewer cases for zolpidem (AHR, 0.84 [95% CI, 0.81-0.87]; P < .001) and triazolam (AHR, 0.82 [95% CI, 0.78-0.87]; P < .001), and no significant difference between suvorexant and eszopiclone. Among those without monotherapy failure, monotherapy was discontinued in 84.6% of patients, with more discontinuations for ramelteon (adjusted odds ratio [AOR], 1.31 [95% CI, 1.24-1.40]; P < .001) and suvorexant (AOR, 1.20 [95% CI, 1.15-1.26]; P < .001) than for eszopiclone and no significant difference between zolpidem or triazolam and eszopiclone. Conclusions and Relevance: Due to uncontrolled confounding factors in this cohort study, no conclusions regarding the pharmacologic properties of guideline-recommended hypnotics can be drawn based on these results. Further studies accounting for confounding factors, including diagnoses of chronic vs acute insomnia disorder, insomnia and psychiatric symptom severity, and physician attitudes toward hypnotic prescription, are needed.

Maternal exposure to zolpidem and risk of specific birth defects.

Zolpidem is a non-benzodiazepine agent indicated for treatment of insomnia. While zolpidem crosses the placenta, little is known about its safety in pregnancy. We assessed associations between self-reported zolpidem use 1 month before pregnancy through to the end of the third month ("early pregnancy") and specific birth defects using data from two multi-site case-control studies: National Birth Defects Prevention Study and Slone Epidemiology Center Birth Defects Study. Analysis included 39,711 birth defect cases and 23,035 controls without a birth defect. For defects with ≥ 5 exposed cases, we used logistic regression with Firth's penalised likelihood to estimate adjusted odds ratios and 95% confidence intervals, considering age at delivery, race/ethnicity, education, body mass index, parity, early-pregnancy antipsychotic, anxiolytic, antidepressant use, early-pregnancy opioid use, early-pregnancy smoking, and study as potential covariates. For defects with three-four exposed cases, we estimated crude odds ratios and 95% confidence intervals. Additionally, we explored differences in odds ratios using propensity score-adjustment and conducted a probabilistic bias analysis of exposure misclassification. Overall, 84 (0.2%) cases and 46 (0.2%) controls reported early-pregnancy zolpidem use. Seven defects had sufficient sample size to calculate adjusted odds ratios, which ranged from 0.76 for cleft lip to 2.18 for gastroschisis. Four defects had odds ratios > 1.8. All confidence intervals included the null. Zolpidem use was rare. We could not calculate adjusted odds ratios for most defects and estimates are imprecise. Results do not support a large increase in risk, but smaller increases in risk for certain defects cannot be ruled out.

Immediate Postoperative Zolpidem Use Increases Risk of Falls and Implant Complication Rates Following Total Hip Arthroplasty: A Retrospective Case-Control Analysis.

BACKGROUND: Zolpidem is the most widely used hypnotic in the United States and has known side effects. However, the morbidity of zolpidem use following total hip arthroplasty (THA) is not well-defined. Thus, the aim of this study was to assess the effects that zolpidem use has on medical and implant complications, falls, lengths of stay, and medical utilizations following THA. METHODS: A retrospective query of a nationwide insurance claims database was conducted from 2010 to 2020. All cases of THA and hypnotic use were identified using procedural and national drug codes. Patients who were prescribed zolpidem within 90 days of surgery were matched to hypnotic naive patients 1:5 based on demographic and comorbidity profiles. The 90-day medical complications, falls, fragility fractures, costs, and readmission rates, as well as 2-year implant complications were compared between cohorts. A total of 50,328 zolpidem patients were matched to 251,286 hypnotic naive patients. RESULTS: The zolpidem group had significantly higher rates of medical complications, falls, and fragility fractures when compared to the hypnotic-naive group. The zolpidem group had significantly higher rates of dislocation, mechanical loosening, and periprosthetic fracture. Likewise, healthcare utilization was significantly greater in the zolpidem group. CONCLUSION: Zolpidem use following THA is associated with significant risk of medical and implant complications, as well as fall risks, increased costs, lengths of stay, and readmissions. The findings of this study may affect discussions between orthopaedic surgeons and their patients on the benefits of sleep quality in their recovery versus the incurred risks of zolpidem use. LEVEL OF EVIDENCE: III, retrospective case-control study.

Zolpidem dependence and withdrawal. A case report of generalized seizures.

Zolpidem is a non-benzodiazepine hypnotic agent used most frequently in the treatment of insomnia, indicated for short-term use. It is not indicated for the chronic treatment of sleep disorders, despite which there is evidence in clinical practice that a large number of patients receive it for years. Although it has been described that it presents a better profile of adverse effects than benzodiazepines and that it generates a lower risk of dependence and withdrawal than these, there are significant reports of cases of dependence and withdrawal from zolpidem. A report of a case of generalized tonic-clonic seizures due to withdrawal at a dose of 300 mg per day of zolpidem is presented and a brief review of the literature is carried out.

Comparative efficacy of hypnotics in young and middle-aged adults with insomnia: a systematic review and network meta-analysis.

OBJECTIVE/BACKGROUND: Insomnia is highly prevalent in modern society. However, the hierarchical selection of hypnotics in young and middle-aged adults with insomnia remains unclear. We aimed to compare the efficacy and daytime drowsiness associated with different hypnotics for treating insomnia in young and middle-aged adults. METHODS: We searched Embase, PubMed, Cochrane Library, and ProQuest Dissertations and Theses A&I databases from inception until December 15, 2021. We also manually searched reference lists and relevant publications. The literature search, data collection, and risk of bias evaluation were all carried out separately by pairs of reviewers. We included randomized control trials (RCTs) that compared hypnotics approved by the Food and Drug Administration. The R and Stata software were both used to perform the meta-analysis. RESULTS: In total, 117 RCTs comprising 22,508 participants with the age of 18 to 65 years were included. Assessment of the efficacy of the hypnotics and adverse events (drowsiness) revealed that zolpidem improved all objective sleep parameters (oTST, oSOL, oWASO, and oSE), zopiclone increased oTST and oSE and reduced oSOL, and daridorexant increased oTST and reduced oWASO. Regarding subjective sleep outcomes, zolpidem exhibited beneficial effects on sTST, sSOL, and sWASO. Zaleplon reduced sSOL, and zopiclone was the recommended hypnotic for improving SQ. Zolpidem was associated with drowsiness effect (odds ratio = 1.82; 95% confidence interval = 1.25 to 2.65). The results of sensitivity analysis remained unchanged after the exclusion of studies reporting long-term effects. CONCLUSION: Zolpidem is recommended for managing sleep-onset insomnia and sleep maintenance insomnia but should be used with caution because of daytime drowsiness effects. Daridorexant is recommended as a promising agent for managing sleep maintenance insomnia.

GABA-A Alpha 2/3 but Not Alpha 1 Receptor Subunit Ligand Inhibits Harmaline and Pimozide-Induced Tremor in Rats.

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.

Occurrence of involuntary movements after prolonged misuse of zolpidem: a case report.

Zolpidem is a non-benzodiazepine agent used for short-term treatment of insomnia. Several cases of dependence and withdrawal from zolpidem are reported in the literature. Furthermore, involuntary movements after prolonged zolpidem misuse have been described. In this case report, a 69-year-old Italian woman with no history of diagnosed psychiatric or neurologic diseases developed uncontrolled movements and a depressive-anxious syndrome after twelve-year zolpidem misuse. The underlying mechanisms of involuntary movements occurring after long-term zolpidem intake are unknown; yet, we suggest that zolpidem might induce an increase in dopamine release through inhibition of gamma-aminobutyric acid neurons tonically suppressing dopamine cells. Future studies on the occurrence of persistent disorders after long-term benzodiazepine or Z-drug abuse are needed and clinicians should pay attention to the risk of tardive syndromes related to zolpidem misuse, especially in the case of long-term intake of over-therapeutic dosages.

Zolpidem use and risk of suicide: A systematic review and meta-analysis.

INTRODUCTION: Zolpidem is one of the most commonly prescribed nonbenzodiazepine hypnotic drugs for insomnia. Published epidemiological studies linked zolpidem with the risk of suicide. However, to date, no meta-analysis investigated this association. Hence, we systematically reviewed and meta-analysed the current evidence from real-world studies reporting the risk of suicide with the use of zolpidem. METHODS: Medline (Ovid), Embase (Ovid), and PsycINFO databases were searched from inception till June 2021 for real-world evidence studies reporting the risk of suicide with the use of zolpidem. The quality assessment of included studies was assessed using the New-Castle Ottawa Scale (NOS). Random-effect meta-analysis was performed using a generic inverse variance method. RESULTS: This meta-analysis was based on four studies with 344,753 participants, of which 42,279 were zolpidem users. The methodological quality of all the included studies was of high quality. A significantly increased risk of suicide or suicide attempt was found in zolpidem users compared to non-users, with a pooled relative risk of 1.88 (95% CI: 1.54 - 2.30). Furthermore, an increased risk of suicidal death was observed in zolpidem users compared to non-users, with a pooled relative risk of 1.82 (95% CI: 1.43 - 2.30). Dose-response analysis also revealed a significantly increased risk of suicide in patients receiving ≥ 180cDDD (cumulative defined daily doses) of zolpidem (124 times), followed by 90-179cDDD (113 times) and <90cDDD (93 times) of zolpidem compared to non-users. CONCLUSION: In conclusion, zolpidem use was associated with an increased risk of suicide or suicide attempt and suicidal death. Therefore, careful prescribing practices must be followed by considering the risk-benefit profile.

Abuse Potential of Lemborexant, a Dual Orexin Receptor Antagonist, Compared With Zolpidem and Suvorexant in Recreational Sedative Users.

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.

Falls, healthcare resources and costs in older adults with insomnia treated with zolpidem, trazodone, or benzodiazepines.

BACKGROUND: Falls are the leading cause of injury-related death among older Americans. While some research has found that insomnia heightens falls, health care resource utilization (HCRU) and costs, the impact of insomnia treatments on fall risk, mortality, HCRU and costs in the elderly population, which could be of substantial interest to payers, has not been fully elucidated. This study evaluated the risk of falls and related consequences among adults ≥ 65 years of age treated with common prescription medications for insomnia compared with non-sleep disordered controls. METHODS: This was a retrospective cohort analysis of deidentified Medicare claims from January 2011 through December 2017. Medicare beneficiaries treated for insomnia receiving zolpidem extended-release, zolpidem immediate-release, trazodone, or benzodiazepines were matched with non-sleep disordered controls. The main outcomes were falls, mortality, healthcare resource utilization (HCRU), and medical costs during the 12 months following the earliest fill date for the insomnia medication of interest. Generalized linear models controlled for several key covariates, including age, race, sex, geographic region and Charlson Comorbidity Index score. RESULTS: The study included 1,699,913 Medicare beneficiaries (59.9% female, mean age 75 years). Relative to controls, adjusted analyses showed that beneficiaries receiving insomnia medication experienced over twice as many falls (odds ratio [OR] = 2.34, 95% CI: 2.31-2.36). In adjusted analyses, patients receiving benzodiazepines or trazodone had the greatest risk. Crude all-cause mortality rates were 15-times as high for the insomnia-treated as controls. Compared with controls, beneficiaries receiving insomnia treatment demonstrated higher estimated adjusted mean number of inpatient, outpatient, and emergency department visits and longer length of inpatient stay. All-cause total adjusted mean costs were higher among insomnia treated patients ($967 vs $454). CONCLUSIONS: Individuals receiving insomnia treatment had an increased risk of falls and mortality and higher HCRU and costs compared with matched beneficiaries without sleep disorders. Trazodone and benzodiazepines were associated with the greatest risk of falls. This analysis suggests that significant risks are associated with common, older generation insomnia medication treatments in the elderly. Nonetheless, these results should be interpreted with caution as the use of these medications may be indicative of underlying morbidity with potential for residual confounding.

The efficacy and safety of zolpidem and zopiclone to treat insomnia in Alzheimer's disease: a randomized, triple-blind, placebo-controlled trial.

No prior studies have evaluated the efficacy and safety of zolpidem and zopiclone to treat insomnia of demented patients. This randomized, triple-blind, placebo-controlled clinical trial used these drugs to treat patients with probable, late onset Alzheimer's dementia (AD) (DSM V and NINCDS-ADRDA criteria) exhibiting insomnia (DSM V criteria and nocturnal NPI scores ≥ 2). Actigraphic records were performed for 7 days at baseline and for 14 days during the treatment period in 62 patients aged 80.5 years in average and randomized at a 1:1:1 ratio for administration of zolpidem 10 mg/day, zopiclone 7.5 mg/day or placebo. Primary endpoint was the main nocturnal sleep duration (MNSD), whereas secondary outcomes were the proportion of the night time slept, awake time after sleep onset (WASO), nocturnal awakenings, total daytime sleep time and daytime naps. Cognitive and functional domains were tested before and after drug/placebo use. Three participants under zopiclone use had intervention interrupted due to intense daytime sedation and worsened agitation with wandering. Zopiclone produced an 81 min increase in MNSD (95% confidence interval (CI): -0.8, 163.2), a 26 min reduction in WASO (95% CI: -56.2, 4.8) and a 2-episode decrease in awakening per night (95% CI: -4.0, 0.4) in average compared to placebo. Zolpidem yielded no significant difference in MNSD despite a significant 22 min reduction in WASO (95% CI: -52.5, 8.3) and a reduction of 1 awakening each night (95% CI: -3.4, 1.2) in relation to placebo. There was a 1-point reduction in mean performance in the symbols search test among zolpidem users (95% CI: -4.1, 1.5) and an almost eight-point reduction in average scores in the digit-symbol coding test among zopiclone users (95% CI: -21.7, 6.2). In summary, short-term use of zolpidem or zopiclone by older insomniacs with AD appears to be clinically helpful, even though safety and tolerance remain issues to be personalized in healthcare settings and further investigated in subsequent trials. This trial was registered in ClinicalTrials.gov Identifier: NCT03075241.

Effects of Bedtime Dosing With Suvorexant and Zolpidem on Balance and Psychomotor Performance in Healthy Elderly Participants During the Night and in the Morning.

PURPOSE/BACKGROUND: This study was designed as an early assessment of the safety of the orexin receptor antagonist suvorexant, but also included exploratory assessments of balance and psychomotor performance that are the focus of this report. METHODS/PROCEDURES: This was a double-blind, randomized, 3-period, crossover, phase 1 study. Balance and psychomotor performance were evaluated during the night in 12 healthy elderly participants after bedtime administration of suvorexant 30 mg (a supratherapeutic dose), the GABAergic agonist zolpidem 5 mg (the recommended dose in the elderly), or placebo. Balance (body sway measured by platform stability) and psychomotor performance (measured by choice reaction time) were assessed predose and at 1.5, 4, and 8 hours postdose in each period. Memory (measured by word recall) was assessed predose and at 4 hours postdose. FINDINGS/RESULTS: At 1.5 hours after nighttime administration of each drug (the approximate time of their anticipated maximal plasma concentrations), both zolpidem and suvorexant increased body sway versus placebo, with a greater increase for zolpidem than suvorexant. Suvorexant increased choice reaction time compared with placebo or zolpidem at 1.5 hours. There were no treatment differences on body sway or choice reaction time at 4 or 8 hours, or on word recall at 4 hours. IMPLICATIONS/CONCLUSIONS: These exploratory data suggest that a 30-mg dose of suvorexant (supratherapeutic) and a 5-mg dose of zolpidem (recommended dose in the elderly) impaired balance at 1.5 hours in healthy elderly people, with potentially less impairment for suvorexant relative to zolpidem, but no treatment differences on body sway or psychomotor performance at 4 and 8 hours. Because of their exploratory nature, these findings and their clinical relevance, if any, require confirmation in a prospective study.

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 ±â€ŠSD from 12.28 ±â€Š3.59 to 9.25 ±â€Š3.99, while in the intervention group the reduction in PSQI score with a mean ±â€ŠSD was from 14.73 ±â€Š4.14 to 10.03 ±â€Š4.04 from baseline to endpoint. However, the EQ5D index score and EQ-visual analogue scale (VAS) at baseline for the control group with a mean ±â€ŠSD was 0.49 ±â€Š0.30 and 50.17 ±â€Š8.65, respectively, while for the intervention group the values were 0.62 ±â€Š0.26 and 47.17 ±â€Š5.82, respectively. The mean EQ5D index score in the control group improved from 0.49 ±â€Š0.30 to 0.53 ±â€Š0.30, but in the intervention group there was no statistical improvement in mean EQ5D index score from 0.62 ±â€Š0.26 to 0.62 ±â€Š0.27 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.

Are Seniors Dependent on Benzodiazepines? A National Clinical Survey of Substance Use Disorder.

Benzodiazepines and Z-drugs, zolpidem and zopiclone, (BZD/Z) are used longer than recommended in the elderly population. However, to date, very few attempts have been made to evaluate dependence on BDZ/Z among the elderly population. We conducted a national multicentric observational prospective study aimed at evaluating the prevalence of and risk factors for dependence among elderly adults. Patients aged 65 or older who were treated with BZD/Z for at least 3 months were evaluated through clinical interviews that conformed to official Diagnostic and Statistical Manual of Mental Disorders (DSM) dependence criteria. Among the 1,024 patients included in the survey, 442 of 976 (45.3%) met the dependence criteria. In the multivariate logistic regression model, dependent patients were categorized as follows: younger (odds ratio (OR) = 0.97), living mostly alone (OR = 1.45), showing psychiatric problems (OR = 2.22), having additional treatments (other than BZD/Z; OR = 1.37), having long-lasting treatment (OR = 1.04), exhibiting significant relationship difficulties (OR = 1.96), committing transgressional behaviors to procure BZD/Z (OR = 2.70), and wanting to stop their consumption of BZD/Z (OR = 7.60). A latent class analysis, which was applied to sort out subgroups within dependent patients, identified two profiles according to the prevalence of dependence items: profile 1 (73%), "withdrawal syndrome when BZD/Z is stopped" (100%) and "previous unsuccessful attempts to stop consumption" (82%); and profile 2 (27%), "tolerance" (76%) and "intake in larger amounts or over a longer period than intended" (86%). BZD/Z dependence is frequent in the elderly population, and among dependent patients, we found two profiles corresponding to positive and negative conditioning of the psychoactive effects of BZD/Z. This study is registered as NCT01920581.

Z-drugs and Falls: A Focused Review of the Literature.

OBJECTIVE: To provide a focused review of the literature related to the association between exposure to Z-drugs and the risk of falls, especially in the older population.
DATA SOURCES: A literature search was conducted using Medline, PsychInfo, and the Cochrane Library database for all clinical trials, case series, and case reports published in English up to May 2020. The search terms used consisted of each Z-drug, including "zolpidem," "zopiclone," "eszopiclone," and "zaleplon," matched with "falls."
STUDY SELECTION: The search yielded 295 studies. After review of abstracts, content and references were reviewed, and duplicates removed, a total of 9 articles met inclusion of exposure to at least 1 Z-drug and a primary outcome of falls.
DATA EXTRACTION: The American Geriatrics Society 2019 Beers Criteria Update for Potentially Inappropriate Medication Use in Older Adults recommends to avoid using nonbenzodiazepine hypnotics in this patient population because of the risk of adverse events.
DATA SYNTHESIS: A majority of the literature suggests an increased risk of falls with exposure to Z-drug use, especially zolpidem. Eight trials examined falls as a primary outcome in non-elderly (n=3) and elderly (n=5) patients in different settings, mostly in an inpatient setting (nursing facility or acute care hospital).
CONCLUSION: Exposure to Z-drugs, especially zolpidem, should be evaluated and counseled on continuously as these medications put patients at an increased risk for falls and other complications.