Impact of benzodiazepine use on the risk of occupational accidents.

Benzodiazepines (BZDs) are drugs commonly used for treating insomnia and anxiety. Although they are known to induce cognitive and psychomotor impairments, their effect on the risk of causing accidents at work remains understudied. The objective of this study is to estimate this risk by differentiating between the recommended use and overuse of these drugs (i.e., uninterrupted use for four months). The data come from the French National Health Data System, which provide a population composed of French people who had at least one work accident (WA) from 2017 to 2019 (approximately 2.5 million people). A linear probability model with two-way fixed effects is used to deal with time-constant heterogeneity and the time effect independent of individuals. The results show a reduction in the risk of WA after a short period of BZD use (one month) compared with no use at all, but the risk of WA increases when treatment exceeds the recommended duration. The intensity of use results in a greater risk of WAs: a 1% increase in BZD use (expressed as the amount reimbursed) leads to a 4.4% (p<0.001) increase in the monthly risk of WAs. Moreover, we see an increase in risk in the month following the treatment discontinuation (+3.6%, p<0.001), which could be due to rebounding and catch-up effects. Health professionals and BZD users should be made aware of the WA risk induced by the use of BZDs, particularly after prolonged use and after discontinuation of treatment. This study provides more evidence for the need to limit the duration of BZD treatment.

Long-term benzodiazepine use and risk of labor market marginalization in Finland: A cohort study with 5-year follow-up.

BACKGROUND: Benzodiazepines and related drugs (BZDRs) are widely used in the treatment of anxiety and sleep disorders, but cognitive adverse effects have been reported in long-term use, and these may increase the risk of labor market marginalization (LMM). The aim of this study was to investigate whether the risk of LMM is associated with new long-term BZDR use compared to short-term use. METHODS: This register-based nationwide cohort study from Finland included 37,703 incident BZDR users aged 18-60 years who initiated BZDR use in 2006. During the first year of use, BZDR users were categorized as long-term users (≥180 days) versus short-term users based on PRE2DUP method. The main outcome was LMM, defined as receipt of disability pension, long-term sickness absence (>90 days), or long-term unemployment (>180 days). The risk of outcomes was analyzed with Cox regression models, adjusted with sociodemographic background, somatic and psychiatric morbidity, other types of medication and previous sickness absence. RESULTS: During 5 years of follow-up, long-term use (34.4%, N = 12,962) was associated with 27% (adjusted Hazard Ratio, aHR 1.27, 95% CI 1.23-1.31) increased risk of LMM compared with short-term use. Long-term use was associated with 42% (aHR 1.42, 95% CI 1.34-1.50) increased risk of disability pension and 26% increased risk of both long-term unemployment and long-term sickness absence. CONCLUSIONS: These results indicate that long-term use of BZDRs is associated with increased risk of dropping out from labor market. This may be partly explained by cognitive adverse effects of prolonged BZDR use, which should be taken into account when prescribing BZDRs.

Avrusning etter bruk av nye rusmidler fra internett.

Background: The knowledge base on new psychoactive substances (NPS) is generally limited. This introduces new challenges and increased unpredictability in substance abuse treatment. Case presentation: A man in his thirties was submitted to detoxification after reportedly using flubromazolam, a high potency designer benzodiazepine, which he had purchased on the dark web. Extensive drug testing of serum, urine and hair, and the remains in a dropper bottle delivered by the patient, did not reveal flubromazolam or possible metabolites, but did reveal several common drugs of abuse, and 8-aminoclonazolam, a metabolite of clonazolam, another designer benzodiazepine sold on the dark web. The detoxification was uncomplicated. An excessive treatment protocol based on the patient's information, involving high preparedness and increased resources, both clinically and analytically, turned out to be unnecessary. Interpretation: The drug use and clinical course in this case proved to be more common than the unit prepared for. The case history illustrates both the challenges with users of NPS and the general unpredictability in substance abuse treatment.

Remimazolam Attenuates LPS-Derived Cognitive Dysfunction via Subdiaphragmatic Vagus Nerve Target α7nAChR-Mediated Nrf2/HO-1 Signal Pathway.

Sepsis-induced neuroinflammation is significantly associated with sepsis-related brain dysfunction. Remimazolam is a novel ultra-short-acting benzodiazepine anesthetic with multiple organ protective effects. However, it is unknown whether remimazolam can ameliorate LPS-induced brain impairment. In this study, Lipopolysaccharide (5 mg/kg, LPS) severely impaired Sprague-Dawley rats spatial learning ability, memory, and cognitive function. However, remimazolam treatment showed a protective effect on LPS-induced cognitive dysfunction. Remimazolam partly reversed LPS-induced splenomegaly, decreased serum cytokine expression, suppressed hippocampal M1 microglial activation, and mitigated oxidative stress injury and neuroinflammation. Electroacupuncture (EA) or PNU282987 treatment improved LPS-induced cognitive dysfunction and also significantly inhibited neuroinflammation and systemic inflammation. However, MLA, ML385, or subdiaphragmatic vagus nerve (SDV) treatment abolished the protective effects of remimazolam. Further mechanistic studies showed that remimazolam induces protective effects by activating subdiaphragmatic vagus nerve target α7nAChR-mediated Nrf2/HO-1 signaling pathway. These results demonstrate that remimazolam can up-regulate α7nAChR, Cyto-Nrf2, HO-1, and cognitive-related (CREB, BDNF, PSD95) protein expressions, suppress M1 microglia, ameliorate neuroinflammation or systemic inflammation, and reverse cognitive dysfunction. Therefore, this study provides insight into a new therapeutic target for the treatment of sepsis-induced cerebral dysfunction.

Association between benzodiazepine coprescription and mortality in people on opioid replacement therapy: a population-based cohort study.

OBJECTIVE: To investigate the association between opioid replacement therapy (ORT) and benzodiazepine (BZD) coprescription and all-cause mortality compared with the prescription of ORT alone. DESIGN: Population-based cohort study. SETTING: Scotland, UK. PARTICIPANTS: Participants were people prescribed ORT between January 2010 and end of December 2020 aged 18 years or above. MAIN OUTCOME MEASURES: All-cause mortality, drug-related deaths and non-drug related deaths. SECONDARY OUTCOME: ORT continuous treatment duration. ANALYSIS: Cox regression with time-varying covariates. RESULTS: During follow-up, 5776 of 46 899 participants died: 1398 while on coprescription and 4378 while on ORT only. The mortality per 100 person years was 3.11 during coprescription and 2.34 on ORT only. The adjusted HR for all-cause mortality was 1.17 (1.10 to 1.24). The adjusted HR for drug-related death was 1.14 (95% CI, 1.04 to 1.24) and the hazard for death not classified as drug-related was 1.19 (95% CI, 1.09 to 1.30). CONCLUSION: Coprescription of BZDs in ORT was associated with an increased risk of all-cause mortality, although with a small effect size than the international literature. Coprescribing was also associated with longer retention in treatment. Risk from BZD coprescription needs to be balanced against the risk from illicit BZDs and unplanned treatment discontinuation. A randomised controlled trial is urgently needed to provide a clear clinical direction. TRIAL REGISTRATION NUMBER: NCT04622995.

Opioid versus Benzodiazepine-based Sedation for Mechanically Ventilated Patients in the Internal Medicine Ward.

BACKGROUND: Opioid-base sedation is considered the first line choice in ventilated patients in intensive care units (ICU). Few studies have examined sedation in ventilated patients outside the ICU. A pilot program was initiated in the internal medicine ward A at Meir Hospital in Kfar Saba, Israel. A new sedation protocol was implemented for opioid-based versus benzodiazepine-based sedation in ventilated patients. OBJECTIVES: To compare the rates and intensity of delirium between patients who received opioid-based sedation vs. benzodiazepine-based sedation. To compare parameters related to morbidity and mortality. METHODS: We conducted a retrospective before-after intervention study based on data collection. Patients who were admitted to the internal medicine ward A from January 2020 to January 2021 and required sedation and ventilation were included. Demographic data, medical history data, admission data, Richmond Agitation and Sedation Scale scores, hemodynamic parameters, reports of falls and self-harm, and data regarding unplanned extubation were collected, as well as the need for additional sedative drugs. RESULTS: Chronic hypertension was more common in the opioid group. Delirium intensity tended to be higher in the benzodiazepine group. The number of ventilation days was significantly higher in the benzodiazepine group, as was the number of times adjuvant sedation was required. CONCLUSIONS: Opioid-based sedation outside the ICU was associated with shorter ventilation days, tendency toward lower intensity of delirium, and reduction in requirement of adjuvant sedative drugs compared to benzodiazepine-based sedation. Further studies are required to confirm the findings.

Prevalence, country-specific prescribing patterns and determinants of benzodiazepine use in community-residing older adults in 7 European countries.

BACKGROUND: The use of benzodiazepines (BZDs) in older population is often accompanied by drug-related complications. Inappropriate BZD use significantly alters older adults' clinical and functional status. This study compares the prevalence, prescribing patterns and factors associated with BZD use in community-dwelling older patients in 7 European countries. METHODS: International, cross-sectional study was conducted in community-dwelling older adults (65 +) in the Czech Republic, Serbia, Estonia, Bulgaria, Croatia, Turkey, and Spain between Feb2019 and Mar2020. Structured and standardized questionnaire based on interRAI assessment scales was applied. Logistic regression was used to evaluate factors associated with BZD use. RESULTS: Out of 2,865 older patients (mean age 73.2 years ± 6.8, 61.2% women) 14.9% were BZD users. The highest prevalence of BZD use was identified in Croatia (35.5%), Spain (33.5%) and Serbia (31.3%). The most frequently prescribed BZDs were diazepam (27.9% of 426 BZD users), alprazolam (23.7%), bromazepam (22.8%) and lorazepam (16.7%). Independent factors associated with BZD use were female gender (OR 1.58, 95%CI 1.19-2.10), hyperpolypharmacy (OR 1.97, 95%CI 1.22-3.16), anxiety (OR 4.26, 95%CI 2.86-6.38), sleeping problems (OR 4.47, 95%CI 3.38-5.92), depression (OR 1.95, 95%CI 1.29-2.95), repetitive anxious complaints (OR 1.77, 95%CI 1.29-2.42), problems with syncope (OR 1.78, 95%CI 1.03-3.06), and loss of appetite (OR 0.60, 95%CI 0.38-0.94). In comparison to Croatia, residing in other countries was associated with lower odds of BZD use (ORs varied from 0.49 (95%CI 0.32-0.75) in Spain to 0.01 (95%CI 0.00-0.03) in Turkey), excluding Serbia (OR 1.11, 95%CI 0.79-1.56). CONCLUSIONS: Despite well-known negative effects, BZDs are still frequently prescribed in older outpatient population in European countries. Principles of safer geriatric prescribing and effective deprescribing strategies should be individually applied in older BZD users.

Risk of suicide attempts and intentional self-harm on alprazolam.

BACKGROUND: From 2000-2021, U.S. suicide deaths have risen 36 %. Identification of pharmacological agents associated with increased suicide risk and safer alternatives may help reduce this trend. METHODS: An exposure-only within-subject time-to-event pharmacoepidemiologic study of the dynamic association between alprazolam treatment and suicide attempts over 2-years. Parallel analyses were conducted for diazepam, lorazepam and buspirone. Data for 2,495,520 patients were obtained from U.S. private insurance medical claims MarketScan from 2010 to 2019. FINDINGS: Alprazolam was associated with over a doubling of risk of suicide attempts (HR=2.21, 95 % CI=2.06,2.38). A duration-response analysis for the modal dose (0.5 mg) revealed a 5 % increase in suicidal events per additional month of treatment (HR=1.05, 95 % CI=1.04,1.07). Parallel analyses with long-acting (diazepam) and short-acting (lorazepam), found similar associations (diazepam HR=2.87, 95 % CI=2.56,3.21; lorazepam HR=1.83, 95 % CI=1.69,2.00), whereas the non-benzodiazepine anxiolytic, buspirone, showed significantly less risk (HR=1.25, 95 % CI=1.13,1.38), and no increased risk in patients with an attempt history (HR=1.05, 95 % CI=0.70,1.59). INTERPRETATION: This study confirmed an earlier signal linking alprazolam to increased suicide attempt risk. The increased risk extends to benzodiazepines in general, regardless of half-life and risk of withdrawal seizure. Buspirone appears to be a safer treatment than benzodiazepines, particularly in patients at increased risk for suicide.

Risperidone-Induced Leukoneutropenia: Evidence from a Positive Rechallenge and Review of the Literature.

Antipsychotics can cause hematologic disorders, and they can have life-threatening consequences. Risperidone, less commonly associated with hematologic adverse effects, is an atypical antipsychotic medication used to treat conditions such as schizophrenia, bipolar disorder and irritability associated with autism. While risperidone primarily affects the central nervous system, it can have some hematologic adverse effects, although these are relatively rare. It is crucial to note that these side effects are not common, and most people taking risperidone do not experience hematologic disorders. The reporting of such disorders may be more frequent with clozapine compared to other atypical antipsychotics because clozapine treatment necessitates regular hematological monitoring 1.

Benzodiazepine Interference with Fertility and Embryo Development: A Preliminary Survey in the Sea Urchin Paracentrotus lividus.

Psychotropic drugs and benzodiazepines are nowadays among the primary substances of abuse. This results in a large and constant release into aquatic environments where they have potentially harmful effects on non-target organisms and, eventually, human health. In the last decades, evidence has been collected on the possible interference of benzodiazepines with reproductive processes, but data are few and incomplete. In this study, the possible negative influence of delorazepam on fertilization and embryo development has been tested in Paracentrotus lividus, a key model organism in studies of reproduction and embryonic development. Sperm, eggs, or fertilized eggs have been exposed to delorazepam at three concentrations: 1 µg/L (environmentally realistic), 5 µg/L, and 10 µg/L. Results indicate that delorazepam reduces the fertilizing capacity of male and female gametes and interferes with fertilization and embryo development. Exposure causes anatomical anomalies in plutei, accelerates/delays development, and alters the presence and distribution of glycoconjugates such as N-Acetyl-glucosamine, α-linked fucose, and α-linked mannose in both morulae and plutei. These results should attract attention to the reproductive fitness of aquatic species exposed to benzodiazepines and pave the way for further investigation of the effects they may exert on human fertility. The presence of benzodiazepines in the aquatic environment raises concerns about the reproductive well-being of aquatic species. Additionally, it prompts worries regarding potential impacts on human fertility due to the excessive use of anxiolytics.

Seizure control and complications in patients switching from clobazam to clonazepam due to drug shortage.

BACKGROUND: Antiseizure medication (ASM) shortages are a global problem that have a negative impact on outcomes such as seizure control in patients with epilepsy (PWE). In the case of clobazam (CLB) shortage, there is no study regarding the management strategy. This study aims to investigate the alteration in seizure frequency and the occurrence of side effects in PWE undergoing an abrupt switch from clobazam (CLB) to clonazepam (CLZ), during CLB shortage. MATERIAL AND METHODS: A retrospective study was conducted from electronic health records at our neurology outpatient clinic from January to July 2022. Change in seizure frequency and percentage of CLZ-associated side effects were determined as primary and secondary outcomes, respectively. Potential drug-drug interactions (Level C and above) were evaluated by using Lexicomp Drug Interaction Checker. RESULTS: The analysis included a total of 29 adult patients (15F, median age: 29). The switching ratio was 10 mg CLB for every 1 mg CLZ (10:1). Seizure frequency was higher during the CLZ period compared to the CLB period (p < 0.05), but no status epilepticus cases were observed. All patients exhibited potential drug-drug interactions, leading to reduced CLZ levels in 12 cases. A total of 36 CLZ-associated side effects were identified, with fatigue (19.4 %), drowsiness (16.6 %), and somnolence (13.8 %) being the most prevalent. A positive and strong correlation was found between CLZ dose and the number of side effects (r: 0.556; p: 0.002). CONCLUSION: The abrupt switch from CLB to CLZ was observed to increase seizure frequency without leading to status epilepticus in PWE. CLZ-associated side effects were found to be tolerable despite the abrupt switch. Future studies may explore the effect of alternative switching ratios.

Exploring clinical applications and long-term effectiveness of benzodiazepines: An integrated perspective on mechanisms, imaging, and personalized medicine.

Benzodiazepines have been long-established treatments for various conditions, including anxiety disorders and insomnia. Recent FDA warnings emphasize the risks of misuse and dependence associated with benzodiazepines. This article highlights their benefits and potential drawbacks from various perspectives. It achieves this by explaining how benzodiazepines work in terms of neuroendocrinology, immunomodulation, sleep, anxiety, cognition, and addiction, ultimately improving their clinical effectiveness. Benzodiazepines play a regulatory role in the HPA axis and impact various systems, including neuropeptide Y and cholecystokinin. Benzodiazepines can facilitate sleep-dependent memory consolidation by promoting spindle wave activity, but they can also lead to memory deficits in older individuals due to reduced slow-wave sleep. The cognitive effects of chronic benzodiazepines use remain uncertain; however, no adverse findings have been reported in clinical imaging studies. This article aims to comprehensively review the evidence on benzodiazepines therapy, emphasizing the need for more clinical studies, especially regarding long-term benzodiazepines use.

Association of antidepressant and benzodiazepine use, and anticholinergic burden with cognitive performance in schizophrenia.

Schizophrenia is characterized by cognitive impairment affecting everyday functioning. Earlier research has hypothesized that antidepressants may associate with better cognitive functioning, but results are mixed. This study explored the association between antidepressant use and cognitive performance in terms of reaction time and visual learning in a clinical sample. In addition, we examined benzodiazepine use and anticholinergic burden. Study participants were drawn from the SUPER-Finland cohort, collected among patients with psychotic illnesses in 2016-2018 throughout Finland (n = 10,410). The analysis included adults with a schizophrenia diagnosis (F20) and results from a cognitive assessment (n = 3365). Information about medications and psychosocial factors were gathered through questionnaire and interview. Cognitive performance was assessed with the Cambridge Neuropsychological Test Automated Battery (CANTAB) with two subtests measuring reaction time and visual learning. Almost 36 % of participants used at least one antidepressant. The use of antidepressants in general was not associated with performance in the reaction time and visual learning tasks. However, the use of SNRI antidepressants was associated with a faster reaction time. Benzodiazepine use and a higher anticholinergic burden were associated with poorer performance in both tests. The results strengthen earlier findings that there is no association between antidepressant use in general and cognitive performance in schizophrenia. However, the association of SNRI medications with a faster reaction time warrants further research. Moreover, the results suggest that more attention should be paid to the anticholinergic burden of the medications used by patients with schizophrenia, as well as avoiding continuous benzodiazepine use.

Patterns of filled prescriptions and the association with risk of drug-induced death. A population-based nested case-control register study.

PURPOSE: Opioid analgesics (OA) and other pharmaceuticals have been associated with drug-induced deaths. However, there is a lack of knowledge regarding patterns of use of these pharmaceuticals in the population and regarding such associations. We identify and describe subgroups of people with different patterns of filled prescriptions of OA and other relevant pharmaceuticals and examine associations with drug-induced deaths. In addition, we estimate the proportion of drug-induced deaths with a filled OA prescription and OA as cause of death. METHODS: A Norwegian population-based nested case-control register study with cases (drug-induced deaths 2010-2018, N = 2388) and population controls matched for age, gender and year of inclusion (N = 21 465). Patterns of filled prescriptions for opioid analgesics (OA), benzodiazepines and benzodiazepine-related drugs, gabapentinoids, ADHD medication and antidepressants/antipsychotics were explored by k-means cluster analysis. Associations with drug-induced deaths were estimated by conditional logistic regression adjusted for sociodemographic characteristics. Overlap of filled OA prescriptions and OA as cause of death was estimated. RESULTS: Five clusters were identified: 'few prescriptions', 'weak OA', 'ADHD medication', 'sedative/psychiatric morbidity' and 'strong OA'. The 'strong OA' cluster had higher socioeconomic status compared to the other groupings. The risk of drug-induced death was also highest in this cluster (OR = 35.5; CI 25.6-49.3) and, for 68% (CI 64-73) of cases, filled prescriptions for OA was indicated as the underlying cause of death. CONCLUSIONS: The cluster analysis identified a subgroup with filled prescriptions of OA and other pharmaceuticals and a higher socioeconomic status than other subgroups. This subgroup had a high risk of drug-induced death that needs to be addressed.

Safety and effcacy of remimazolam tosilate for sedation during combined spinal-epidural anesthesia for orthopedic procedures: a randomized controlled trial.

OBJECTIVE: The objective of this study was to assess the efficacy and safety of Remimazolam in the context of combined spinal-epidural anesthesia for sedation during orthopedic surgery. METHODS: This randomized controlled trial enrolled patients scheduled for orthopedic surgery under combined spinal-epidural anesthesia (N = 80), who were randomly allocated to receive either dexmedetomidine (Group-D) or remimazolam (Group-R). The target sedation range aimed for a Ramsay score of 2-5 or a BIS value of 60-80 to evaluate the effectiveness and safety of remimazolam during sedation. RESULTS: The time taken to achieve the desired level of sedation was significantly shorter in the remimazolam group compared to the dexmedetomidine group (3.69 ± 0.75 vs. 9.59 ± 1.03; P < 0.0001). Patients in the remimazolam group exhibited quicker recovery, fewer intraoperative adverse events, more consistent vital signs, and greater satisfaction at various time points throughout the surgery. CONCLUSION: This preliminary study demonstrates that remimazolam tosilate serves as a safe and effective sedative for orthopedic surgery performed under combined spinal-epidural anesthesia, in comparison with dexmedetomidine.

Improving patient experience for people prescribed medicines with a risk of dependence or withdrawal: co-designed solutions using experience based co-design.

BACKGROUND: Significant concerns have been raised regarding how medications with a risk of dependence or withdrawal are managed and how care is experienced by patients. This study sought to co-design solutions to improve the experience of care for patients prescribed benzodiazepines, z-drugs, opioids for chronic non-cancer pain, gabapentinoids and antidepressants. METHOD: Twenty patients and fifteen healthcare professionals from five different GP practices were recruited to take part. The study used Experience Based Co-Design. Patients and healthcare professionals completed semi-structured interviews and took part in feedback groups and co-design workshops to collaboratively identify priorities for improvement and to co-design solutions to improve the experience of care. RESULTS: Poor patient experience was common among people prescribed medications with a risk of dependence or withdrawal. Patients and healthcare professionals identified three main priority areas to improve the experience of care: (i) ensuring patients are provided with detailed information in relation to their medication, (ii) ensuring continuity of care for patients, and (iii) providing alternative treatment options to medication. Solutions to improve care were co-designed by patients and healthcare staff and implemented within participating GP practices to improve the experience of care. CONCLUSION: Good patient experience is a key element of quality care. This study highlights that the provision of in-depth medication related information, continuity of care and alternative treatment to medication are important to patients prescribed medicines with a risk of dependence or withdrawal. Improving these aspects of care should be a priority for future improvement and delivery plans.

Real-World Effectiveness of High-Dose Olanzapine and Clozapine for Treatment-Resistant Schizophrenia in Japan: A Retrospective Bidirectional Mirror-Image Study.

BACKGROUND: Clozapine is considered the gold standard medication for treatment-resistant schizophrenia (TRS). However, given that clozapine treatment is associated with the burden of regular blood monitoring and the risk of life-threatening adverse effects, high-dose olanzapine can serve as an alternative treatment. We conducted a bidirectional mirror-image study to evaluate the effectiveness of high-dose olanzapine compared with clozapine. METHODS: We included patients with TRS who switched from olanzapine to clozapine or switched from clozapine to olanzapine, and received high-dose (>20 mg/d) olanzapine treatment for ≥4 weeks at Yamanashi Prefectural Kita Hospital. We obtained data on hospitalization, seclusion, and modified electroconvulsive therapy (mECT) during the clozapine phase and the olanzapine phase. RESULTS: A total of 44 patients were included. When patients switched from high-dose olanzapine to clozapine (n = 32), significant reductions were found in the total days of seclusion, the total number of mECT, and the number of patients who received mECT at least once. When patients switched from clozapine to high-dose olanzapine (n = 12), a significant reduction was found in the number of patients who received mECT at least once. When data from both directions of treatment were combined, significant reductions were found in the total days of seclusion, the total number of mECT, and the number of patients who received mECT at least once in favor of clozapine. CONCLUSIONS: Findings suggest that high-dose olanzapine may not be as effective as clozapine for patients with TRS in real-world practice. However, it should be noted that there are unique circumstances that restrict the use of clozapine in Japan.

Trends in Pregabalin Use and Prescribing Patterns in the Adult Population: A 10-Year Pharmacoepidemiologic Study.

BACKGROUND AND OBJECTIVE: Pregabalin is steadily gaining popularity worldwide, with epidemiological studies indicating an increase in labeled, off-labeled, and recreational uses. In Israel, pregabalin prescriptions are not regulated by the controlled substances legislations, prompting a need to examine its usage trends for potential policy adjustments. The objective of this study was to assess trends in pregabalin prescribing during a 10-year period, to characterize demographic and clinical characteristics of individuals prescribed pregabalin, and to identify risk factors associated with high-intensity pregabalin use. METHODS: This retrospective, longitudinal study examined trends in pregabalin prescribing from 2010 to 2019 based on data extracted from the Clalit Health Services (CHS) electronic database. Annual pregabalin prescribing rate was calculated individually for each reporting year. A univariable analysis was conducted to compare the demographic and clinical characteristics of pregabalin users in 2019 with those in 2010. Multivariable regression analysis was performed to assess dose-related patterns by specific demographic and clinical characteristics. RESULTS: Pregabalin prescription rate more than doubled over 10 years [odds ratio (OR) 2.3, p = 0.001], reaching 7.2 [95% confidence interval (CI) 7.18-7.28] prescriptions per 100 CHS members in 2019. The highest prescription rates were observed among the elderly population (13.2 and 24.1 prescriptions per 100 CHS members for those aged 55-74 and over 75 years old, respectively). Same-year administration of pregabalin with opioids, benzodiazepines, and Z-drugs was common; however, the percentage of patients using these drugs together declined in 2019 compared with 2010 (p < 0.001). Males, patients with low socioeconomic status, patients aged 35-54 years, and those who consumed opioids, benzodiazepines, and Z-drugs received higher pregabalin doses. CONCLUSION: Pregabalin use has increased significantly in the Israeli adult-based CHS population, consistent with worldwide data. A growing use over time may indicate overprescription. More studies are needed on misuse patterns to identify populations most susceptible to high-dose and high-intensity pregabalin use.