Clinical Drug Investigation最新文献

{"title":"Off-Label Prescription of Benzodiazepines: A Retrospective Cohort Study of Prescribing Prevalence in Primary Care.","authors":"Kevin Trimm, Maria-Teresa Moraga, Bärbel Knäuper, Elham Rahme, Emily Gibson McDonald, Robyn Tamblyn","doi":"10.1007/s40261-025-01476-1","DOIUrl":"https://doi.org/10.1007/s40261-025-01476-1","url":null,"abstract":"<p><strong>Background and objectives: </strong>Benzodiazepines are commonly prescribed medications approved for and used in the treatment of anxiolytic and sleep disorders, as well as for seizures, and alcohol withdrawal. However, benzodiazepines are also controlled substances because of their potential for abuse and personal harm, which are especially prevalent among older people. It is therefore important to understand how benzodiazepines are being prescribed, and the prevalence of off-label benzodiazepine prescribing, of which very little is known because of challenges in documenting treatment indication. The aim of this study was to detail the prevalence of benzodiazepine off-label prescribing.</p><p><strong>Methods: </strong>Data from the MOXXI (Medical Office of the XXIst century) electronic health record system in Quebec Canada were used, where specifying the treatment indication for each prescription is required, to estimate the prevalence of off-label prescribing and indications for off-label use of benzodiazepines. Each drug indication was retrospectively classified as either on-label or off-label according to the Health Canada drug database. Off-label prescriptions were further classified as having class congruence supporting their prescription if another benzodiazepine had been approved for the indication by Health Canada.</p><p><strong>Results: </strong>There were 20,125 (17.0%) adult patients prescribed benzodiazepines out of the 118,223 patients enrolled in the MOXXI system. The patients were predominantly female (65.6%) and tended to be older with an average age of 60.14 years at the time of the first benzodiazepine prescription. A total of 101,583 unique prescriptions were written for 14 different benzodiazepines. An approximately equal number of benzodiazepines were prescribed on- and off-label (49.3% on-label, 49.2% off-label). Most off-label prescription indications were classified as having class congruence (95.2%).</p><p><strong>Conclusions: </strong>Benzodiazepines were frequently prescribed in the province of Quebec and were prescribed off-label approximately half of the time. When prescribed off-label, we found that most of these prescriptions were for indications that were approved for other benzodiazepines. The most common indication for off-label benzodiazepine prescriptions with class congruence was insomnia.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Multiple Oral Doses of a Glycine Transporter 1 Inhibitor, Iclepertin (BI 425809), on the Steady-state Pharmacokinetics of a Combined Oral Contraceptive Containing Ethinylestradiol and Levonorgestrel: a Phase I Clinical Trial in Healthy Females.","authors":"Shilpa Madari, Yesilda Balavarca, Yury Shatillo, Corey Reuteman-Fowler, Michael Desch","doi":"10.1007/s40261-025-01472-5","DOIUrl":"https://doi.org/10.1007/s40261-025-01472-5","url":null,"abstract":"<p><strong>Background: </strong>Iclepertin is a selective inhibitor of glycine transporter 1 recently investigated as a novel treatment for cognitive impairment associated with schizophrenia. Iclepertin is a potential mild inducer of liver cytochrome P450 3A4, which metabolises ethinylestradiol and levonorgestrel, which are used in combined oral contraceptives (OCs).</p><p><strong>Objectives: </strong>This trial investigated the potential drug interaction effect of steady-state iclepertin on the steady-state pharmacokinetics of combined OCs.</p><p><strong>Methods: </strong>This phase I, non-randomised, open-label, two-period, fixed-sequence trial was conducted in healthy pre-menopausal female volunteers aged 18-35 years. In period 1, participants received a combined OC (ethinylestradiol 30 µg/levonorgestrel 150 µg once daily; reference treatment). In period 2, participants received a combined OC and iclepertin 10 mg once daily (test treatment). Primary pharmacokinetic endpoints of ethinylestradiol or levonorgestrel in plasma at steady state over a uniform dosing interval τ were area under the concentration-time curve (AUC_τ,ss) and maximum and minimum measured concentration (C_max,ss and C_min,ss); drug interaction potential was estimated by geometric mean ratios (test treatment/reference treatment) with two-sided 90% confidence intervals (CIs) using analysis of variance. Safety assessments included monitoring adverse events (AEs).</p><p><strong>Results: </strong>In total, 19 participants entered the trial; 17 were treated (periods 1 and 2). Steady-state pharmacokinetics of ethinylestradiol and levonorgestrel were similar with and without iclepertin; geometric mean ratios for AUC_τ,ss, C_max,ss, and C_min,ss were slightly above 100%, and 90% CIs were within standard bioequivalence boundaries (80-125%). The number of on-treatment AEs was similar in period 1 (n = 13) and period 2 (n = 15); AEs were of mild-to-moderate severity.</p><p><strong>Conclusion: </strong>Iclepertin 10 mg had no meaningful effect on the pharmacokinetics of ethinylestradiol and levonorgestrel, suggesting that these drugs can be administered concomitantly.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov (NCT05613777; registered on 18 October 2023).</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting the Role of Serotonin in Attention-Deficit Hyperactivity Disorder: New Insights from Preclinical and Clinical Studies.","authors":"Matia B Solomon, Brittney Yegla, Jeffrey H Newcorn, Vladimir Maletic, Jonathan Rubin, Trevor W Robbins","doi":"10.1007/s40261-025-01473-4","DOIUrl":"https://doi.org/10.1007/s40261-025-01473-4","url":null,"abstract":"<p><p>Attention-deficit hyperactivity disorder (ADHD) is characterized by core symptoms of inattention, hyperactivity, and impulsivity. Aberrant dopaminergic and noradrenergic neurotransmission are often implicated in the pathogenesis of these symptoms because ADHD treatments increase synaptic levels of these neurotransmitters in brain regions associated with attention and impulse control. However, some ADHD treatments also enhance serotonergic neurotransmission in these regions, which could contribute to their efficacy. Here, we review preclinical and clinical data highlighting functional interactions between the serotonergic and catecholaminergic systems in mediating ADHD phenotypes and responses to treatment. The potential utility of serotonergic compounds for treating distinct behavioral features and psychiatric comorbidities (e.g., depression) is also discussed. Overall, preclinical and clinical studies underscore important neuromodulatory effects of serotonin on the catecholaminergic system in mediating distinct ADHD behavioral phenotypes, notably hyperactivity-impulsivity and emotional dysregulation. Incorporating a basic understanding of dynamic monoaminergic interactions and their contributions to ADHD symptoms may identify new targets for treatment. Beyond ADHD core symptoms, emotional dysregulation, which is closely linked to serotonergic dysfunction, is common in ADHD and significantly contributes to negative outcomes across the lifespan. Therefore, an expanded conceptualization of ADHD that includes emotional dysregulation may facilitate insight into ADHD pathology and treatment.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Memantine for the Treatment of Primary Negative Symptoms in Schizophrenia: A Meta-analysis of Randomized Controlled Trials.","authors":"Houlin Hong, Jack Donlon, Martin Schaefer, Susanne Sarkar, Dragana Bugarski-Kirola, Mujeeb U Shad, Wei Hou, Matthias Kirschner, Sajoy P Varghese, Ludmil Mitrev, Valentina Echeverria, John Dibato, Selene R T Veerman, Rohit Aiyer, Thomas N Ferraro, Gerardo Villarreal, Shafiqur Rahman, Trevor W Stone, Maju M Koola","doi":"10.1007/s40261-025-01465-4","DOIUrl":"10.1007/s40261-025-01465-4","url":null,"abstract":"<p><strong>Background: </strong>Memantine is an N-methyl-D-aspartate (NMDA) receptor antagonist with favorable safety and side effect profiles. There is a growing body of evidence for memantine as an adjunctive therapy for the positive, negative, and cognitive symptoms of schizophrenia.</p><p><strong>Objective: </strong>This meta-analysis examined the efficacy of memantine as an add-on to treatment with antipsychotic(s) for the primary negative symptoms (PNS) of schizophrenia.</p><p><strong>Methods: </strong>We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and searched for relevant publications in PubMed, Cochrane Library, PsycINFO, Embase, and China Journal Net databases from inception using the following search terms: memantine, schizophrenia, randomized controlled trials (RCTs), RCT, and clinical trial. Searches were limited to English- and Chinese-language articles to date. Standardized mean differences (SMDs) with 95% confidence intervals were calculated using RevMan 5.4 to assess the effect size. Risk of bias was assessed using RoB 2.0.</p><p><strong>Results: </strong>In total, 13 RCTs were identified (N = 681). Memantine was superior to placebo in treating negative symptoms, with an SMD of 0.79 (p = 0.0001, N = 631, 12 RCTs). Analysis of three studies whose corresponding authors provided original datasets showed an SMD of 2.16 (p = 0.25, N = 97) after adjusting for change in psychosis, depression, and extrapyramidal symptoms, suggesting that memantine is efficacious in treating PNS. Additionally, cognitive testing significantly improved, with an SMD of 0.66 (p = 0.0001, N = 395, eight RCTs). Positive symptoms were not significantly improved (SMD = 0.24, p = 0.1, N = 631, 12 RCTs).</p><p><strong>Conclusions: </strong>To our knowledge, this is the first study showing a large effect size for treating PNS with memantine. Although statistical significance was not reached because of the small sample size (N = 97), the results were as expected because drugs such as memantine that act at NMDA receptors are unlikely to be effective as stand-alone treatments. Future RCTs should evaluate NMDAergic drugs in combination with complementary medications to optimize therapeutic effects for all three domains of schizophrenia psychopathology.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"627-642"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SDZ-AFL: An Aflibercept Biosimilar.","authors":"Yahiya Y Syed","doi":"10.1007/s40261-025-01458-3","DOIUrl":"10.1007/s40261-025-01458-3","url":null,"abstract":"<p><p>SDZ-AFL (SOK583A1; Afqlir^®) is a biosimilar of the reference intravitreal aflibercept, a vascular endothelial growth factor inhibitor. SDZ-AFL has been approved in the EU for the treatment of the same indications in adults as reference aflibercept: neovascular age-related macular degeneration (nAMD), visual impairment due to macular oedema secondary to retinal vein occlusion, visual impairment due to diabetic macular oedema and visual impairment due to myopic choroidal neovascularisation. SDZ-AFL has similar physicochemical and pharmacodynamic properties to those of reference aflibercept, and pharmacokinetic similarity has been demonstrated in patients with nAMD. SDZ-AFL demonstrated clinical efficacy equivalent to that of reference aflibercept in patients with nAMD and was generally well tolerated in this population. The tolerability, safety and immunogenicity profiles of SDZ-AFL were similar to those of reference aflibercept. The role of reference aflibercept in the management of neovascular retinal diseases is well established, and SDZ-AFL provides an effective biosimilar alternative for patients requiring ophthalmic aflibercept therapy.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"677-680"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relative Bioavailability of Single-Dose Oral Administration of Two SHR7280 Formulations (Dry Suspension and Tablets) in Healthy Chinese Volunteers.","authors":"Xian Liu, Ruzhai Qin, Chang Shu, Kai Shen, Xi Li, Lingyu Ma, Xiaomei Li, Lanping Li, Jiao Peng, Dongxiang Huang, Sihan Chen, Zhihong Xie, Lika Ye, Lian Duan","doi":"10.1007/s40261-025-01470-7","DOIUrl":"10.1007/s40261-025-01470-7","url":null,"abstract":"<p><strong>Background: </strong>SHR7280 is an oral small-molecule gonadotropin-releasing hormone (GnRH) antagonist that can be developed as therapeutic agent for the treatment of hormone-dependent pathologies, including prostate, breast, and ovarian cancers. SHR7280 dry suspension formulation is being developed to provide an alternative mode of administration for order patients, those using nutritional tubes, and those unable to swallow solid dosage forms.</p><p><strong>Objective: </strong>This study evaluated the relative bioavailability, pharmacokinetics (PK), and safety of SHR7280 dry suspension and tablets administered in a single dose in healthy Chinese volunteers.</p><p><strong>Methods: </strong>A randomized, open, two-preparation, two-sequence, two-cycle, double-crossover design was used in this study. The plasma drug concentration was determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The main PK parameters of the two formulations of SHR7280 were calculated by noncompartmental analysis using Phoenix WinNonlin (version 8.3.4) software. A total of 16 healthy participants were randomized to receive SHR7280 (200 mg) as tablets (n = 8) or dry suspension (n = 8) formulation.</p><p><strong>Results: </strong>The geometric least squares mean ratio (90% confidence interval [CI]) for maximum concentration of drug in blood plasma (C_max) and area under the plasma concentration-time curve from time 0 to t (AUC_0-t) and from time 0 to infinity (AUC_0-∞) between the dry suspension of SHR7280 and its tablets were calculated as follows: C_max-101.90% (90% CI 79.50-130.62), AUC_0-t-111.58% (90% CI 91.71-135.76), and AUC_0-∞-111.44% (90% CI 91.70-135.43). A total of nine (56.3%) subjects experienced treatment-emergent adverse events (TEAEs).</p><p><strong>Conclusions: </strong>The bioavailability of SHR7280 tablets was found to be comparable to that of dry suspension. The safety profile of two formulations was favorable. No serious adverse events or adverse drug reactions were reported.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov (NCT05868057; 22 May 2023).</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"643-650"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spontaneous Reports of Adverse Reactions with Fatal Outcomes After COVID-19 Vaccination During the National Vaccination Campaign in Sweden.","authors":"Marja-Leena Nurminen, Per Lindemo, Anders Sundström, Björn Zethelius, Maria Larsson, Sofia Attelind, Nicklas Pihlström, Rickard Ljung, Veronica Arthurson","doi":"10.1007/s40261-025-01466-3","DOIUrl":"10.1007/s40261-025-01466-3","url":null,"abstract":"<p><strong>Background and objectives: </strong>Reports of suspected adverse drug reactions are of a great importance for the safety monitoring of new vaccines to identify potential safety risks promptly and to ensure necessary measures for risk mitigation. We reviewed the reports of fatal adverse drug reactions after coronavirus disease 2019 (COVID-19) vaccination with Comirnaty^®, Spikevax^®, and Vaxzevria^® during the national vaccination campaign in Sweden.</p><p><strong>Methods: </strong>Swedish reports of suspected adverse drug reactions with fatal outcomes after COVID-19 vaccines were retrieved from the EudraVigilance database. Vaccination data were obtained from the National vaccination register. Reporting rates were calculated by dividing the number of adverse drug reaction reports with fatal outcomes by the number of people exposed to at least one dose of the COVID-19 vaccines or by the number of vaccine doses given. A causality assessment of adverse drug reaction reports was performed by clinically qualified reviewers.</p><p><strong>Results: </strong>More than 26 million doses of COVID-19 vaccines were administered and 456 reports of suspected adverse drug reactions with fatal outcomes were reported during 27 December, 2020-31 May, 2023. The reporting rate was 5.7 fatal outcomes per 100,000 persons vaccinated with at least one dose of any COVID-19 vaccine or 1.7 per 100,000 vaccine doses given. Most of the fatalities were related to patients' pre-existing conditions, predominantly among people aged 70 years or older. Only ten of the reported fatalities (0.1 per 100,000 persons vaccinated) were assessed as consistent with a causal association to COVID-19 vaccination.</p><p><strong>Conclusions: </strong>Adverse drug reactions with fatal outcomes after COVID-19 vaccines in Sweden were very rare. No new safety concerns were observed in this study.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"665-675"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost-Effectiveness of Adding Dapagliflozin and Empagliflozin to Standard Treatment for Diabetic Kidney Disease in China.","authors":"Tingting Qiu, Ping Li, Dan Yan","doi":"10.1007/s40261-025-01462-7","DOIUrl":"10.1007/s40261-025-01462-7","url":null,"abstract":"<p><strong>Background: </strong>Dapagliflozin and empagliflozin are emerging as promising treatment options for diabetic kidney disease (DKD).</p><p><strong>Objective: </strong>This study sought to evaluate the cost effectiveness of incorporating dapagliflozin and empagliflozin into the standard treatment for DKD in China.</p><p><strong>Methods: </strong>A Markov model was constructed to evaluate the cost-effectiveness of dapagliflozin and empagliflozin plus standard treatment versus standard treatment alone for DKD treatment from a healthcare perspective. Costs and utility data was obtained from published literatures within the Chinese context. The primary outcome included total cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). GDP per capita of 2023 in China (¥89,358) was utilized as the willingness-to-pay threshold.</p><p><strong>Results: </strong>Compared to standard treatment alone, add-on therapy of dapagliflozin or empagliflozin resulted in a higher total cost than those solely receiving standard treatment (+¥19,203.56 and +¥9496.92, respectively). However, both dapagliflozin and empagliflozin also yielded more life-years (+1.72 vs. +1.40) and QALYs (+1.40 vs. +0.88). The ICER per life-year and ICER per QALY was ¥11,178.52 and ¥18,192.50 for dapagliflozin and ¥6773.10 and ¥10,811.64 for empagliflozin, respectively. The incremental net monetary benefit was ¥75,120.54 and ¥68,994.90 for dapagliflozin and empagliflozin, respectively. Sensitivity analysis supported the main findings of the base-case analysis as the cost-effectiveness of dapagliflozin or empagliflozin was sustained for most plausible ranges of parameter values.</p><p><strong>Conclusions: </strong>Considering that the ICER falls below the predefined willingness-to-pay threshold, incorporating dapagliflozin and empagliflozin into standard treatment for DKD is likely to be a cost-effective strategy in China.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"651-664"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitomycin Intravesical Solution: First Approval.","authors":"Susan J Keam","doi":"10.1007/s40261-025-01475-2","DOIUrl":"https://doi.org/10.1007/s40261-025-01475-2","url":null,"abstract":"<p><p>Mitomycin intravesical solution (ZUSDURI^TM), a hydrogel formulation of the DNA synthesis inhibitor mitomycin, has been developed by UroGen Pharma, Inc. for the treatment of low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC) via intravesical instillation. In June 2025, mitomycin intravesical solution was approved for the treatment of recurrent LG-IR-NMIBC in the USA. This article summarizes the milestones in the development of mitomycin intravesical solution leading to this first approval for LG-IR-NMIBC.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pregabalin and Methadone Plasma Levels in Patients Receiving Methadone Maintenance Treatment: An Observational Study.","authors":"Anat Sason, Miriam Adelson, Shaul Schreiber, Einat Peles","doi":"10.1007/s40261-025-01460-9","DOIUrl":"10.1007/s40261-025-01460-9","url":null,"abstract":"<p><strong>Background and objectives: </strong>The combination of pregabalin and opioid usage is a known risk for fatalities. The pregabalin misuse rate among patients in methadone maintenance treatment (MMT) is reported to be high. However, pregabalin's risk among MMT patients, specifically concerning methadone dose and plasma level, is not yet determined. We aimed to study retention, survival, and whether pregabalin misuse is related to methadone dose and plasma level in MMT patients.</p><p><strong>Methods: </strong>An observational study was conducted on 273 patients at the MMT clinic in Tel Aviv, Israel. Inclusion criteria required having urine drug-screening results for pregabalin when evaluated for methadone plasma levels. Methadone dose and plasma level, drug in urine, sociodemographic, and addiction variables were taken from patients' records.</p><p><strong>Results: </strong>Patients with positive urine for pregabalin (n = 50) were comparable to 223 negative patients tested in methadone dose (124.3 ± 30.7 vs. 117.1 ± 42.5, p = 0.3) but had higher methadone plasma levels (693.8 ± 327.6 vs. 572.3 ± 286.5 ng/ml, p = 0.009) and QTc intervals on ECG (422.8 ± 31.8 vs. 412.1 ± 29.8 ms, p = 0.03). Logistic regression model found pregabalin tested positive as more likely to test positive for benzodiazepine (OR = 9.1), methylphenidate (OR = 5.5), and fentanyl (OR = 5.9), and to have higher methadone plasma levels (OR = 1.002). Cumulative retention (p < 0.001) and survival (p = 0.007) since admission to MMT were both shorter in the pregabalin group.</p><p><strong>Conclusions: </strong>Patients who tested positive for pregabalin presented high methadone plasma levels, even though they were treated with normal or low methadone doses. This phenomenon highlights the importance of monitoring methadone levels, which is not a routine procedure, to reduce patients' risk.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"575-582"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}