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.

Polifarmácia e cognição em pacientes com idade avançada / Polypharmacy and cognition in elderly patients

Objetivo: Avaliar a prevalência da polifarmácia e da prescrição de medicações inapropriadas, bem como suas associações com a capacidade cognitiva e funcional do idoso. Métodos: Estudo observacional transversal, no qual foram analisadas as medicações prescritas em 141 prontuários para pacientes acima de 50 anos, em associação com testes que quantificaram a capacidade funcional e cognitiva deles. Resultados: Observou-se média de 4,41 medicamentos por paciente, sendo que 0,41 deles foram considerados inapropriado, segundo o critério de Beers. Verificou-se também relação estatisticamente significativa quanto ao número de medicações e testes que mediam a capacidade funcional e cognitiva dos idosos. Conclusão: O aumento da polifarmácia e da prescrição de medicações potencialmente inadequadas acarretou significativa piora da capacidade cognitiva e funcional do idoso

Objective: To evaluate the prevalence of polypharmacy and of the prescription of inappropriate medications, as well as their associations with the cognitive and functional capacity of the elderly. Methods: Cross-sectional observational study which analyzed the drugs prescribed in 141 medical records for patients over 50 years of age, associated with tests that quantified their functional and cognitive capacity. Results: An average of 4.41 medications per patient was observed, and 0.41 were considered inappropriate according to the Beers criteria. There was also a statistically significant relation regarding the number of medications and tests that measure the functional and cognitive capacity of the elderly. Conclusion: The increase in polypharmacy and in the prescription of potentially inappropriate medications led to a significant impairment of the cognitive and functional capacity of the elderly

Association between colorectal cancer and zolpidem use in a case-control study.

This study aimed to examine the association between colorectal cancer and zolpidem use in Taiwan.A case-control study was conducted using the database of Taiwan National Health Insurance Program from 2000 to 2013. Participants aged 20 to 84 years with newly diagnosed colorectal cancer were selected as the cases. Sex-matched and age-matched participants without colorectal cancer were randomly selected as the matched controls. The odds ratio and 95% confidence interval for colorectal cancer associated with zolpidem use were calculated by the multivariable logistic regression model.There were 4912 cases with colorectal cancer and 4912 matched controls without colorectal cancer. The mean age was 63 years and 58% were male participants. After adjustment for co-variables, the multivariable logistic regression model disclosed that there was no statistical association between colorectal cancer and zolpidem use (adjusted OR 1.05, 95% CI 0.95-1.15).No statistical association can be detected between colorectal cancer and zolpidem use in Taiwan.

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 1, 2008, to Oct 3, 2018; with searches of MEDLINE, Embase, and PsycINFO, and the Cochrane and King's Fund libraries), an open call-for-evidence on patient experience and service evaluations, and a retrospective, patient-linked analysis of the National Health Service (NHS) Business Services Authority prescription database (April 1, 2015, to March 30, 2018) for all adults aged 18 years and over. Indirectly (sex and age) standardised rates (ISRs) were computed for all 195 NHS Clinical Commissioning Groups in England, containing 7821 general practices for the geographical analysis. We used publicly available mid-year (June 30) data on the resident adult population and investigated deprivation using the English Indices of Multiple Deprivation (IMD) quintiles (quintile 1 least deprived, quintile 5 most deprived), with each patient assigned to the IMD quintile score of their general practitioner's practice for each year. Statistical modelling (adjusted incident rate ratios [IRRs]) of the number of patients who had a prescription dispensed for each medicine class, and the number of patients in receipt of a prescription for at least 12 months, was done by sex, age group, and IMD quintile. FINDINGS: 77 articles on the five medicine classes were identified from the literature search and call-for-evidence. 17 randomised placebo-controlled trials (6729 participants) reported antidepressant-associated withdrawal symptoms. Almost all studies were rated of very low, low, or moderate quality. The focus of qualitative and other reports was on patients' experiences of long-term antidepressant use, and typically sudden onset, severe, and protracted withdrawal symptoms when medication was stopped. Between April 1, 2017, and March 31, 2018, 11·53 million individuals (26·3% of residents in England) had a prescription dispensed for at least one medicine class: antidepressants (7·26 million [16·6%]), opioids (5·61 million [12·8%]), gabapentinoids (1·46 million [3·3%]), benzodiazepines (1·35 million [3·1%]), and Z-drugs (0·99 million [2·3%]). For three of these medicine classes, more people had a prescription dispensed in areas of higher deprivation, with adjusted IRRs (referenced to quintile 1) ranging from 1·10 to 1·24 for antidepressants, 1·20 to 1·85 for opioids, and 1·21 to 1·85 for gabapentinoids across quintiles, and higher ISRs generally concentrated in the north and east of England. In contrast, the highest ISRs for benzodiazepines and Z-drugs were generally in the southwest, southeast, and east of England, with low ISRs in the north. Z-drugs were associated with increased deprivation, but only at the highest quintile (adjusted IRR 1·11 [95% CI 1·01-1·22]). For benzodiazepines, prescribing was reduced for people in quintiles 4 (0·90 [0·85-0·96]) and 5 (0·89 [0·82-0·97]). In March, 2018, for each of medicine class, about 50% of patients who had a prescription dispensed had done so continuously for at least 12 months, with the highest ISRs in the north and east. Long-term prescribing was associated with a gradient of increased deprivation. INTERPRETATION: In 1 year over a quarter of the adult population in England had a prescription dispensed for antidepressants, opioids (for non-cancer pain), gabapentinoids, benzodiazepines, or Z-drugs. Long-term (>12 months) prescribing is common, despite being either not recommended by clinical guidelines or of doubtful efficacy in many cases. Enhanced national and local monitoring, better guidance for personalised care, and better doctor-patient decision making are needed. FUNDING: Public Health England.

Prescription Medications for the Treatment of Insomnia and Risk of Suicide Attempt: a Comparative Safety Study.

IMPORTANCE: Guidelines for the pharmacological treatment of chronic insomnia in adults recognize that trazodone and other off-label medications are commonly prescribed despite poor evidence. The Department of Veterans Health Affairs (VA) fills high volumes of inexpensive, over-the-counter sedating antihistamines and older antidepressants in addition to benzodiazepines and zolpidem. Yet little is known about the comparative safety of these agents with regard to suicidal behavior. OBJECTIVES: To assess the comparative effectiveness of the safety of medications routinely used to treat insomnia in VA. DESIGN: Comparative effectiveness using propensity score-matched samples. SETTING: VA. PARTICIPANTS: VA patients without any history of suicidal ideation or behavior 12 months prior to first exposure. EXPOSURES: VA formularies and data were used to identify prescriptions for insomnia. Agents accounting for at least 1% of total insomnia fill volume were < 200 mg trazodone, hydroxyzine, diphenhydramine, zolpidem, lorazepam, diazepam, and temazepam. Exposure was defined as an incident monotherapy exposure preceded by 12 months without any insomnia medications. Subjects with insomnia polypharmacy or cross-overs in the 12 months following first exposure were excluded. MAIN OUTCOMES AND MEASURES: Suicide attempts within 12 months of first exposure. RESULTS: Three hundred forty-eight thousand four hundred forty-nine subjects met criteria and three well-balanced cohorts by drug class matched to zolpidem were created. After adjusting for days' supply, mental health history, and pain and central nervous system medication history, hazard ratios (compared to zolpidem) were as follows: (< 200 mg) trazodone (HR = 1.61, 95% CI 1.07-2.43); sedating antihistamines (HR = 1.37, 95% CI 0.90-2.07); and benzodiazepines (HR = 1.31, 95% CI 0.85-2.08). CONCLUSIONS AND RELEVANCE: Compared to zolpidem, hazard of suicide attempt was 61% higher with trazodone (< 200 mg). No significant differences in suicide attempt risk were identified between benzodiazepines or sedating antihistamines and zolpidem, respectively. These findings provide the first comparative effectiveness evidence against the use of trazodone for insomnia.