Pharmacoepidemiology and Drug Safety最新文献

{"title":"CodeMergeR: A Shiny-Based Application for Codelist Integration.","authors":"Vjola Hoxhaj, Judit Riera-Arnau, Sima Mohammadi, Miriam C J M Sturkenboom, Constanza L Andaur Navarro","doi":"10.1002/pds.70491","DOIUrl":"10.1002/pds.70491","url":null,"abstract":"<p><strong>Objective: </strong>To describe CodeMergeR, an open-source R shiny application developed within the VAC4EU network for the standardization, cleaning, and integration of individual concept codelists into a master file for real-world evidence (RWE) studies.</p><p><strong>Materials and methods: </strong>CodeMergeR was designed to process codelists exported by CodeMapper v1.0. The application includes two modules: (1) Conformance and Coherence, which checks file naming conventions, metadata consistency, and structural integrity; and (2) Cleaning and Standardization, which removes duplicates, corrects formatting issues where a valid match is available, flags and excludes uncorrectable codes (e.g., scientific notation, dashes). Functional and performance testing were conducted using real-world library metadata and codelists from the VAC4EU library, including manually introduced errors to assess detection capabilities.</p><p><strong>Results: </strong>The CodeMergeR identified a wide range of structural and semantic issues, achieving an overall error detection rate of 96.8% (61/63 errors). Depending on the issue type, detected errors were either automatically corrected (e.g., rounding, when a validated code was found), flagged and excluded from the master codelist if unresolved (e.g., scientific notation, dashes), or flagged for manual review (e.g., metadata mismatches, missing concepts). Processing of 50 clinical concept folders and 10 Algorithms completed in under 1 min during performance testing.</p><p><strong>Discussion: </strong>CodeMergeR detected structural and formatting errors with an accuracy of 96.8%, supporting its use as a quality-check step prior to deploying codelists in analytical pipelines. In contrast to existing, CodeMergeR fills a distinct quality assurance role in codelist generation and transparency.</p><p><strong>Conclusion: </strong>CodeMergeR contributes to improved reproducibility, scalability, and transparency in codelist management in RWE studies.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 10","pages":"e70491"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13620201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Treatment Patterns in Norwegian ADHD-Medicine Users: A Cohort Register-Based Study With 5 Years of Follow-Up, 2012-2021.","authors":"Espen Anker, Anne Halmøy, Mats Fredriksen","doi":"10.1002/pds.70486","DOIUrl":"10.1002/pds.70486","url":null,"abstract":"<p><strong>Purpose: </strong>To improve interpretation of long-term ADHD medication treatment trajectories in Norway by examining sex- and age-specific persistence, distinguishing within-substance product switching from active-ingredient (ATC substance) switching, and describing the medication and prescriber context of the last observed dispensation before non-persistence.</p><p><strong>Methods: </strong>This study used population-based data from the Norwegian Prescription Database (NorPD) to identify 33 706 incident users initiating ADHD medication in 2012-2016, defined using an individual-specific 5-year look-back. Participants were followed for up to 5 years until 2021. We estimated dispensing-based persistence, defined non-persistence as the first dispensing gap of ≥ 396 days/13 months, characterised switching as either within-substance product switching or active-ingredient (ATC substance) switching, and described the last dispensed medication and prescriber specialty recorded before non-persistence.</p><p><strong>Results: </strong>The cohort included 19 898 men (59%) and 13 808 women (41%); 97%-98% initiated methylphenidate. Five-year persistence was 39% in men and 35% in women. During follow-up, 41% had no switch and 26% had ≥ 4 switches. Among first switches, within-substance product switching predominated (80.9% in men; 77.5% in women), while active-ingredient switching was less common (19.1% and 22.5%, respectively). Among those who met the non-persistence definition during follow-up (62.4%), the last dispensed medication was methylphenidate (76%), atomoxetine/guanfacine (12%), lisdexamfetamine (7%), and dexamphetamine (3%), respectively; the last prescriber specialty recorded on the last dispensation was a general practitioner for 51.9% and a specialist for 48.1%.</p><p><strong>Conclusions: </strong>In Norway, most incident ADHD medication users met a dispensing-based definition of non-persistence within 5 years. Switching was frequent, but most first switches occurred within the same active substance rather than between substances, suggesting that many observed changes in dispensing data may reflect product substitution or formulation change rather than a true change in pharmacological strategy. These findings may improve interpretation of long-term treatment trajectories.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 10","pages":"e70486"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing Real-World Evidence With Clinical Trials in Juvenile Idiopathic Arthritis.","authors":"Stephen J Balevic, Timothy Beukelman, Thomas Phillips, Colleen Correll, Ann McMahon","doi":"10.1002/pds.70492","DOIUrl":"10.1002/pds.70492","url":null,"abstract":"<p><strong>Objective: </strong>To compare the clinical characteristics and outcomes of children with juvenile idiopathic arthritis (JIA) treated with biologic drugs in traditional clinical trials with the real-world data (RWD) in the CARRA Registry.</p><p><strong>Methods: </strong>This was a retrospective observational study. We reviewed data from 3192 children in the CARRA Registry with JIA exposed to adalimumab or canakinumab, 2 historical trials of polyarticular JIA participants exposed to adalimumab (n = 171 and 32), and 1 trial for canakinumab in systemic JIA (n = 43). We made matched and unmatched comparisons of demographic information and the ACR-Pedi response rate based on trial eligibility criteria.</p><p><strong>Results: </strong>Very few children in the CARRA Registry would have been eligible for the historical clinical trials: < 10% for adalimumab and < 5% for canakinumab. There was a longer duration of follow-up and a wider range of body size in the CARRA Registry compared with the historical clinical trials. When matched on trial inclusion, the ACR-Pedi response rates broadly aligned with those observed in the trials for adalimumab, whereas the sample size for canakinumab limited comparisons for the response rate.</p><p><strong>Conclusion: </strong>Children encountered in clinical practice had wider ranges of body size and less severe disease at drug initiation. These results underscore that registration trials may be enriched for patients with more severe disease and are not fully representative of the broader JIA population who use these drugs after marketing. Real-world evidence generated from observational data may play an increasingly important role in regulatory decision making, along with the continued need for controlled clinical trials.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 10","pages":"e70492"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149113210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pregnancy Outcome After First-Trimester Exposure to Statins: Study Results Based on the Embryotox Cohort.","authors":"Evelin Beck, Andrea T Adelsberger, Katarina Dathe","doi":"10.1002/pds.70481","DOIUrl":"10.1002/pds.70481","url":null,"abstract":"<p><strong>Purpose: </strong>This observational cohort study aimed to assess the risk of adverse pregnancy and neonatal outcomes in pregnancies exposed to statins during the first trimester, given that the use of statins during pregnancy remains controversial. The primary study endpoints were the rates of spontaneous abortion and major birth defects.</p><p><strong>Methods: </strong>In total, 188 pregnancies exposed to statins in the first trimester were compared with a cohort of 564 pregnancies without the study medication, which were recorded at the Embryotox Centre between January 2000 and June 2021. The effect of statin exposure on pregnancy outcome was estimated using Cox proportional hazards regression models. Log-binomial regression was used to evaluate the risk of major birth defects.</p><p><strong>Results: </strong>Major birth defects were observed in 10 of 135 (7.4%) infants in the statin cohort and in 12 of 501 (2.4%) infants in the comparison cohort (RR 3.09, 95% CI 1.37-7.00). After adjustment for relevant baseline covariates and additional maternal disease factors, the difference substantially attenuated (RRadj 2.16; 95% CI 0.88-5.31). The cumulative incidence of spontaneous abortion was 26.8% in the statin-exposed versus 15.0% in the comparison cohort (HR 1.86, 95% CI 1.13-3.04; HRadj 1.66, 95% CI 0.99-2.78).</p><p><strong>Conclusions: </strong>Current evidence suggests that statins are not major teratogens. The observed associations between statin exposure and birth defects, as well as unfavourable pregnancy outcomes, are presumably influenced by confounding factors such as underlying maternal disease. Our study results lend support to this assumption. However, they should be interpreted cautiously due to the limited cohort size.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 10","pages":"e70481"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13618450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149070059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Importance of the Unit of Analysis: Presentation-Level Records Versus Notifications in Brazil's Medicines Discontinuation Dashboard.","authors":"Amancio Henrique Damasceno-Rodrigues, Daniel Tenório da Silva, Elisdete Maria Santos de Jesus","doi":"10.1002/pds.70495","DOIUrl":"10.1002/pds.70495","url":null,"abstract":"","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 10","pages":"e70495"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149113283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Algorithms to Identify Preeclampsia in Routinely Collected Healthcare Data: A Systematic Review.","authors":"Julie Scotto, Anna Beckmeyer-Borowko, Sonia Guleria, Eman A Alghamdi, Susan E Andrade, Sonia M Grandi, Ditte Mølgaard-Nielsen, Maryline Le Noan-Lainé, Elena Rivero-Ferrer, Meritxell Sabidó Espin, Sandra Lopez-Leon","doi":"10.1002/pds.70490","DOIUrl":"10.1002/pds.70490","url":null,"abstract":"<p><strong>Importance: </strong>Preeclampsia is a leading cause of maternal morbidity and mortality globally. As real-world data sources are increasingly used for maternal health surveillance and pharmacoepidemiologic studies, valid algorithms are essential for accurately identifying preeclampsia in routinely collected healthcare data.</p><p><strong>Objective: </strong>To identify and characterize algorithms used to ascertain preeclampsia in population-based healthcare databases, summarize validation metrics, and describe the range of reported prevalence estimates.</p><p><strong>Evidence review: </strong>Following PRISMA guidelines of 2021, PubMed was searched for studies published from January 1, 2010, to July 1, 2025. Observational studies using reproducible code-based algorithms to identify preeclampsia in routinely collected healthcare data were included. Screening and full-text review were performed in duplicate, with discrepancies resolved by a third reviewer. Data extraction focused on algorithm definitions, coding systems, validation methods, and epidemiologic estimates. A total of 289 studies met inclusion criteria, including 13 validation studies.</p><p><strong>Findings: </strong>Across included studies, 43.6% used Nordic nationwide registries, 30.1% used claims databases, and 12.1% used electronic health records. ICD-10 O14.x was used in nearly all studies; inclusion of O11.x and O15.x varied. Validation studies consistently demonstrated high specificity (> 90%) but low sensitivity (≤ 80%), reflecting under-ascertainment when relying solely on diagnosis codes. More than 70% of studies did not report start or end points for the time window of ascertainment. Reported prevalence ranged from 0.6% to 6.6% across case definitions and settings. The prevalence of severe preeclampsia ranged from 0.6% to 2.2%. Algorithms including O11.x, O14.x, and O15.x showed improved sensitivity in some settings.</p><p><strong>Conclusions and relevance: </strong>Algorithms for identifying preeclampsia in real-world data are highly specific but variably sensitive, with substantial heterogeneity in coding definitions and ascertainment windows. Standardized reporting and consistent inclusion of O11.x, O14.x, and O15.x may improve comparability, reproducibility, and the accuracy of epidemiologic estimates across data sources. High-specificity algorithms may be particularly useful for comparative safety studies, whereas potential under-ascertainment should be considered when estimating incidence or prevalence.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 10","pages":"e70490"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Introduction to Concepts in Artificial Intelligence and Machine Learning for Pharmacoepidemiologists: Large Language Models.","authors":"James M Gwinnutt, Rodrigo de Oliveira, Miriam J Haviland, Julien H Shippee, Elizabeth Eldridge, Lenon Mendes Pereira, Emily Bratton, Jay Nanavati, Christina DeFilippo Mack","doi":"10.1002/pds.70452","DOIUrl":"10.1002/pds.70452","url":null,"abstract":"<p><p>Large language models (LLMs) represent a type of generative artificial intelligence (GenAI) that generate and interpret text, with some LLMs able to process multimodal content (e.g., images, audio, video), and can be deployed as part of agents to perform users' tasks. LLMs can perform natural language processing functions such as summarization, translation, and extraction giving them the potential to enhance and scale pharmacoepidemiological and real-world research by performing tasks such as literature review, data extraction, and medical writing. Despite the growing integration of GenAI tools into research workflows, their technical foundations and methodological implications remain unfamiliar to many pharmacoepidemiologists, who are often responsible for the reliability and accuracy of research that relies on these tools. This paper aims to inform pharmacoepidemiologists about the capabilities and limitations of LLMs to support responsible integration into the field of pharmacoepidemiology, providing an intuitive overview of how LLMs work, focusing on training and text generation, and reviews current and emerging applications in drug effectiveness and safety research and epidemiology. The article addresses challenges associated with LLM use in real-world evidence generation, including concerns regarding reproducibility, bias, hallucinations, plagiarism, data privacy, and the need for validation.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 10","pages":"e70452"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13593388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-Discharge Antiseizure Medication Use and Poststroke Survival: An Emulated Target Trial in Older Adults.","authors":"Madhav Sankaranarayanan, Maria A Donahue, Julianne D Brooks, Shuo Sun, Joseph P Newhouse, Deborah Blacker, Sebastien Haneuse, Sonia Hernández Díaz, Lidia M V R Moura","doi":"10.1002/pds.70489","DOIUrl":"10.1002/pds.70489","url":null,"abstract":"<p><strong>Purpose: </strong>Levetiracetam is commonly prescribed for seizure prophylaxis after acute ischemic stroke (AIS) and often continued beyond discharge. While its short-term effectiveness for preventing poststroke seizures is established, it is unclear whether prolonged use improves survival, particularly in older adults. We estimated the effect of continued levetiracetam use on 90-day mortality among Medicare beneficiaries after AIS.</p><p><strong>Methods: </strong>Using Traditional Medicare claims data (2008-2021), we identified beneficiaries aged ≥ 65 years hospitalized for AIS who initiated outpatient levetiracetam within 90 days of discharge. After 1 month of continued poststroke levetiracetam use (start of follow-up), we compared 90-day mortality between patients with a new levetiracetam dispensation within a 14-day grace period post-follow-up and those without one. We performed cloning, censoring, and weighting to address immortal-time bias and estimated standardized mortality risks, risk differences, and 95% confidence intervals (CIs).</p><p><strong>Results: </strong>Among 3212 eligible beneficiaries, 1779 (55.4%) received a new levetiracetam dispensation within the 14-day grace period. After adjustment for demographics, hospitalization characteristics, timing of initiation, and comorbidities, continued use was associated with lower 90-day mortality than discontinuation (53 vs. 62 deaths per 1000; risk difference -9 per 1000; 95% CI: -12, -5).</p><p><strong>Conclusion: </strong>Among older Medicare beneficiaries who initiated levetiracetam after AIS, continued outpatient use was associated with lower short-term 90-day mortality, particularly among patients aged ≥ 75 years. These findings should not be interpreted as support for routine or indefinite continuation, because the claims-based design cannot assess seizure recurrence, functional outcomes, quality of life, treatment indication, or potential neuropsychiatric harms.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 10","pages":"e70489"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temporal Trends in Patient Characteristics, Anticoagulation Treatment Quality, and Clinical Outcomes of Individuals Receiving Vitamin K Antagonists in the Netherlands (2014 Until-2022).","authors":"Gilda D Zielinski, Qingui Chen, Marieke J H A Kruip, Frederikus A Klok, Suzanne C Cannegieter, Nienke van Rein","doi":"10.1002/pds.70494","DOIUrl":"10.1002/pds.70494","url":null,"abstract":"<p><strong>Objectives: </strong>To describe temporal trends in the clinical landscape of vitamin K antagonist (VKA) treatment in the Netherlands, after the introduction of a lower international normalized ratio (INR) target range in 2016 and direct oral anticoagulants.</p><p><strong>Methods: </strong>Data from 17 Dutch anticoagulation clinics between 2014 and 2022 were individually linked to nationwide healthcare data. Prevalent VKA users were identified on January 1 of each year, forming nine annual cohorts. We assessed baseline patient characteristics, anticoagulation treatment quality (using time in/above/below therapeutic range [TTR/ATR/BTR]), and annual odds ratios of major bleeding and thromboembolism for each cohort.</p><p><strong>Results: </strong>The number of patients treated with VKAs increased from 101 090 in 2014 to 121 916 in 2017, followed by a decline to 73 649 in 2022. Over time, cohorts were characterized by increasing age and a higher prevalence of comorbidities, with a doubling of kidney disease. After the introduction of the lower INR target range, mean BTR decreased (~30% in 2014 to ~15% in 2022), while mean TTR increased (~54% in 2014 to ~67% in 2022), with stable mean ATR. Across calendar years, the 1-year odds ratio of major bleeding decreased from 1.71% (95% CI 1.63-1.79) in 2014 to 1.52% (95% CI 1.44-1.61) in 2022, whereas the odds ratio of ischemic stroke/transient ischemic attack/systemic thromboembolism increased from 1.14% (95% CI 1.08-1.21) in 2014 to 1.32% (95% CI 1.24-1.40) in 2022. The 1-year odds ratio of mortality increased from 5.09 (95% CI 4.95-5.22) to 8.55 (95% CI 8.35-8.75), with an OR of 1.74 (95% CI 1.68-1.81).</p><p><strong>Conclusions: </strong>VKA users declined between 2014 and 2022. The remaining patients using VKA became older and more comorbid. During this period, INR target ranges were lowered, while temporal changes were observed with decreasing odds ratio of major bleeding and increasing odds ratio of thromboembolism and mortality.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 10","pages":"e70494"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain Penetrant Calcium Channel Blockers Were Not Associated With Reduced Alcohol Consumption: Converging Results From Two Large Independent Cohort Studies Using Electronic Health Records.","authors":"Christopher T Rentsch, Vanessa A Palzes, Mingjian Shi, Michael R Setzer, Samantha G Malone, Andrea H Kline-Simon, Emma L Winterlind, Lorenzo Leggio, Vincent Lo Re, David A Fiellin, John Tazare, Mehdi Farokhnia, Stacy Sterling, Henry R Kranzler, Joshua C Gray","doi":"10.1002/pds.70487","DOIUrl":"10.1002/pds.70487","url":null,"abstract":"<p><strong>Purpose: </strong>Alcohol use disorder (AUD) remains a major public health problem, with few effective treatments. L-type calcium channel blockers (LTCCBs) have genetic and preclinical support as potential treatments for AUD.</p><p><strong>Methods: </strong>We evaluated whether brain penetrant (BP)-LTCCBs are associated with reduced alcohol consumption in two preregistered observational cohort studies using electronic health records from the US Department of Veterans Affairs (VA) and Kaiser Permanente Northern California (KPNC). New users of BP-LTCCBs (nifedipine or felodipine) were compared with new users of a non-BP-LTCCB (amlodipine) and with unexposed patients from the same clinics, requiring a 180-day washout and ≥ 60 days' supply. Propensity score matching was performed across all exposure contrasts. The primary outcome was change in drinks per week from pre-index to end of follow-up using difference-in-differences (DiD) models, with prespecified subgroup analyses by AUD diagnosis, drinking level, and sex.</p><p><strong>Results: </strong>Across both health systems, BP-LTCCB initiation was not associated with greater reductions in drinks per week than either comparator, with broadly consistent findings across all subgroups; though some subgroups were small and imprecise. In the VA, the DiD comparing BP-LTCCB with non-BP-LTCCB was 0.14 drinks/week (95% CI -0.06, 0.34), and versus unexposed was 0.00 (95% CI -0.18, 0.19). Similar results were observed in KPNC (BP-LTCCB vs. non-BP-LTCCB: 0.31, 95% CI -0.48, 1.11; BP-LTCCB vs. unexposed: 0.16, 95% CI -0.67, 0.99).</p><p><strong>Conclusions: </strong>In two large, preregistered EHR-based cohorts, we found no evidence that BP-LTCCBs were associated with reduced drinking relative to comparators. Despite compelling genetic and preclinical evidence, these findings do not support repurposing BP-LTCCBs for AUD and instead prioritize alternative pharmacologic targets.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 10","pages":"e70487"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13616991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149070085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}