Pharmacological Clinical Trials Research Articles

ω‑3 fatty acids in atherosclerotic cardiovascular disease (Review).

Atherosclerotic cardiovascular disease (ASCVD) is one of the most common chronic diseases in the world. Epidemiological evidence and clinical trials have shown that ω-3 fatty acids have a variety of promoting effects in reducing the risk of ASCVD, but different conclusions of large randomized controlled trials make their clinical use in the prevention and treatment of ASCVD controversial. The present review focuses on the pharmacological mechanism, clinical trials and evidence value of clinical applications of ω-3 fatty acids in order to provide theoretical and practical evidence for the clinical application strategy, and follow-up research and development of ω-3 fatty acids as anti-ASCVD drugs.

Treatment discontinuation in pharmacological clinical trials for gambling disorder

BackgroundGambling disorder affects 0.5–2% of the population, and of those who receive treatment, dropout tends to be relatively high. Very little is known about participant-specific variables linked to treatment discontinuation/dropout in gambling disorder, especially in pharmacological clinical trial settings. MethodsData were pooled from eight previous randomized, controlled pharmacological clinical trials conducted in people with gambling disorder. Demographic and clinical variables were compared between those who did versus did not subsequently dropout from those treatment trials. ResultsThe sample comprised data from 635 individuals, and the overall rate of treatment dropout was 40%. Subsequent treatment dropout was significantly associated with the following: positive family history of gambling disorder in one or more first degree relatives (relative risk [RR] of dropout in those with positive history vs not = 1.30), preference for mainly strategic vs non-strategic gambling activities (RR = 1.43), lower levels of education (Cohen's D = 0.22), and higher levels of functional disability (Cohen's D = 0.18). These variables did not differ significantly as a function of treatment condition (medication versus placebo). Dropouts and completers did not differ significantly in terms of the other demographic or clinical variables that were considered. ConclusionsThis study identified several candidate participant-specific predictors of pharmacological treatment dropout in gambling disorder. The findings highlight the need for future studies to address a wider range of contextual variables at large scale (including also study-specific variables e.g. trial/intervention duration), including in naturalistic treatment and clinical trial settings, with a view to developing algorithms that might usefully predict dropout risk.

Frailty in clinical drug trials: Frailty assessments, subgroup analyses and outcomes.

With population ageing, drug trials are increasingly turning their attention to including older, frailer people. This review aimed to provide an overview of how frailty was assessed in published studies related to clinical pharmacological trials, and on the interaction of frailty on the efficacy of the treatments. We searched MEDLINE, EMBASE and Cochrane for clinical drug trials in older people. A total of 4031 abstracts were screened and 17 relevant studies were included in this review. We summarized the findings of these 17 trials into five main clinical areas: cardiovascular (eight studies), cognition (one study), vaccination (two studies), cancer (four studies) and other (two studies). Frailty was assessed retrospectively in most of the studies. Frailty was treated as an ordinal variable (with different levels of frailty) or binary variable (frail/non-frail) using cut-offs in some studies, and as a continuous in some other studies. The effect of frailty on the treatment efficacy was not consistent among the studies. While several trials, such as the Action in Diabetes and Vascular Disease-Preterax and Diamicron Modified Release Controlled Evaluation trials, the Systolic Blood Pressure Intervention Trial and the Aspirin in Reducing Events in the Elderly trial, showed some reduced effects of the treatment in frail patients, most of the trials showed that the benefits of the treatment are not affected by frailty. Some trials even showed that the benefits of the treatment were more significant in frailer patients (the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure and the Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure trials). The results of this review suggest that routine measurement of frailty in participants in clinical drug trials would improve our knowledge of the effect of treatment in the frail and identify those who have more or least to gain from treatment.

Harnessing Big Data in Amyotrophic Lateral Sclerosis: Machine Learning Applications for Clinical Practice and Pharmaceutical Trials.

The arrival of genotype-specific therapies in amyotrophic lateral sclerosis (ALS) signals the dawn of precision medicine in motor neuron diseases (MNDs). After decades of academic studies in ALS, we are now witnessing tangible clinical advances. An ever increasing number of well-designed descriptive studies have been published in recent years, characterizing typical disease-burden patterns in vivo and post mortem. Phenotype- and genotype-associated traits and "typical" propagation patterns have been described based on longitudinal clinical and biomarker data. The practical caveat of these studies is that they report "group-level", stereotyped trajectories representative of ALS as a whole. In the clinical setting, however, "group-level" biomarker signatures have limited practical relevance and what matters is the meaningful interpretation of data from a single individual. The increasing availability of large normative data sets, national registries, extant academic data, consortium repositories, and emerging data platforms now permit the meaningful interpretation of individual biomarker profiles and allow the categorization of single patients into relevant diagnostic, phenotypic, and prognostic categories. A variety of machine learning (ML) strategies have been recently explored in MND to demonstrate the feasibility of interpreting data from a single patient. Despite the considerable clinical prospects of classification models, a number of pragmatic challenges need to be overcome to unleash the full potential of ML in ALS. Cohort size limitations, administrative hurdles, data harmonization challenges, regulatory differences, methodological obstacles, and financial implications and are just some of the barriers to readily implement ML in routine clinical practice. Despite these challenges, machine-learning strategies are likely to be firmly integrated in clinical decision-making and pharmacological trials in the near future.

Tegoprazan as a New Remedy for Gastrointestinal Diseases in Comparison with its Therapeutic Predecessors: A Mini-Review.

Potassium-competitive acid blockers (P-CABs), such as tegoprazan, are a new and diverse class of drugs that can completely block the potassium-binding site of gastric H+/K+ ATPase, potentially overcoming the limitations of proton-pump inhibitors (PPIs). A number of studies have compared the effectiveness as well as the safety profile of tegoprazan to PPIs and other P-CABs for the treatment of gastrointestinal diseases. The current review study evaluates the published works of literature related to clinical pharmacology and clinical trials of tegoprazan for the treatment of diseases related to the gastrointestinal tract. The findings of this study revealed that tegoprazan is safe and well-tolerated and can be used to treat a group of gastrointestinal diseases, including gastroesophageal reflux disease (GERD), non-erosive reflux disease (NERD), and H. pylori infection.

Formulation and evaluation of herbal chocolate from Arjuna Bark- treatment of heart disease condition

In the indigenous medical system, Terminalia arjuna is one of the most widely used and advantageous medicinal herbs for the treatment of cardiovascular disorders. This thorough analysis offers the most recent information on the traditional uses, phytochemistry, pharmacological data, toxicological data, clinical efficacy, safety and efficacy of Terminalia arjuna. It also lays out plans for further study and development to substantiate the plant's therapeutic potential through scientific means. A thorough web and library search of numerous indexed and non-indexed journals, some local literature and a variety of publications published on ethnopharmacology, phytochemistry and traditional usage were used to gather information about Terminalia arjuna. Regarding the effectiveness and safety profile of Terminalia arjuna, numerous pre-clinical (2000–2014) and clinical investigations (1990–2014) have also been taken into consideration. The pleiotropic advantages associated with Terminalia arjuna, comprising its anti-atherogenic, hypotensive, inotropic, anti-inflammatory, anti-thrombotic and antioxidant properties, have been demonstrated in numerous in vitro, in vivo and clinical investigations. These effects can be used to treat a variety of cardiovascular problems. There is sample evidence to support the plant's good safety profile when combined with other traditional medications. The precise molecular mechanism of its action, the best way to administer the medication, whether to employ an alcoholic, watery or crude extract, toxicological research and how it interacts with other medications are all poorly understood. This review concludes by emphasizing the significance of Terminalia arjuna, as well as its pleiotropic effects and functional characteristics particularly in relation to cardiovascular disorders. Even though a number of pharmacological research and clinical trials back up its traditional use in treating CVD, more rigorous, state-of-the-art clinical trials with larger sample sizes are necessary to evaluate Terminalia arjuna purported efficacy.

Traditional uses, Phytochemistry and Pharmacology of Asparagus adscendens Roxb.: A Review

Background: Musali (Asparagus adscendens Roxb.) is a traditionally important medicinal plant of the family Asparagaceae. It is used worldwide to treat several ailments due to the presence of various bioactive constituents, mainly concentrated in the tubers of plants. It has been used since time immemorial as a popular drug for treating chronic leucorrhea, spermatorrhea, general weakness, diarrhea, dysentery, and pharmacological purposes like rejuvenation, aphrodisiac, etc. This review aimed to gather information on the traditional uses, phytochemistry, and pharmacology of Asparagus adscendens Roxb. Materials and methods: Primarily, classical literatures of Ayurveda, including Brihat-trayi (greater triad), Laghu-trayi (lesser triad), and Nighantus (lexicons), were reviewed for the terms “Musali” and “Shweta Musali.". Establishing an overview, library resources, and online collections of books and original research articles, other online databases such as Pubmed Central, Scopus, Embase, Web of Science, ERIC, IEEE Xplore, ScienceDirect, DOAJ, JSTOR, Henari, Google Scholar, and NepJoL were explored with search words like “Musali”, “Safed Musali”, “Shweta Musali” “Asparagus adscendens”, botanical characteristics, traditional and contemporary uses, pharmacognosy, phytochemical constituents, pharmacology, agriculture, and miscellaneous aspects. Ethnobotanical reports, wet laboratory experiments, pharmacognostic characteristics, phytoconstituents, and pharmacology (experimental works and clinical trials) are selected to include in this review. Evidence-based papers from indexed sources were also considered. Results and discussion: Asparagus adscendens has been used for the treatment of chronic leucorrhea, spermatorrhea, general weakness, diarrhea, dysentery, rejuvenation, and aphrodisiacs in Ayurveda by its various names and formulations since 1000 BC, the period of Agnivesa. This plant has great pharmacological actions such as antifertility, antioxidant, anthelminthic, antidiabetic, etc. Conclusion: Musali has been a unique gift of nature to mankind since time immemorial. It is a major ingredient in many Ayurvedic formulations. It has several uses, including as a strong "Rasayana" (rejuvenator), a tonic and vitalizer that promotes health, a therapeutic remedy for prenatal and postnatal problems, a restorative agent that boosts immunity, and a strong aphrodisiac. It will take a number of scientific endeavors to investigate the pharmacological actions that are hidden and described in the classics. To assess the pharmacotherapeutics of Asparagus adscendens and provide a solid, evidence-based treatment, more clinical studies may be carried out.

Normalization and cross-sectional validation of an extended Adverse Event Profile (E AEP) in a large cohort of patients with epilepsy

PurposeThe Liverpool Adverse Event Profile (L AEP) is commonly used in clinical practice and pharmacological trials for the monitoring of side effects of anti-seizure medication (ASM). However potentially unrelated, additional symptoms and normative data should be considered to put patients´ complaints into perspective. MethodsAn extended 32-item AEP (E AEP) was given to 537 healthy subjects and 1,605 patients with epilepsy as part of the Bonn ASM side effect registry. The tool was factor-analyzed, corrected for age, gender, and repeated application, and related to drug load and individual substances (with N> 100) on item and scale level (total E AEP and its subscales cognition, dizziness, energy, mood, bodily symptoms, aggression, and sexuality). ResultsCompared to non-normalized results, at item level, between one and two-thirds of responses suggesting impairment were found to be unlikely to be related to ASM treatment after normalization. Binary regression analyses revealed differential effects of medication choice, but also of antidepressants and neuroleptics on complaint domains. The explained variance was better for physical than psychological domains. The results reflect both known drug side effects and indications. Patients´ explicit attribution of problems to their medications barely improved the correlation of the E AEP and treatment parameters. ConclusionApplication of a norm-referenced AEP is highly recommended to avoid overestimation of treatment related problems in patients with epilepsy. It allows evaluation on item and scale level for individuals as well as groups in drug trials. Plausible relations to individual drugs and to drug load can be demonstrated. The explanatory power was better for physical than psychological domains. Drug-related complaint patterns reflect known drug side effects (e.g. perampanel and brivaracetam with aggression) as well as drug indications (e.g. lamotrigine for depression). This is likely to be particularly relevant when side effects may have affected treatment decisions. Longitudinal evaluation with repeated application of the E AEP with changes of drug treatment is in progress.

Quercetin as a Therapeutic Product: Evaluation of Its Pharmacological Action and Clinical Applications-A Review.

Quercetin is the major polyphenolic flavonoid that belongs to the class called flavanols. It is found in many foods, such as green tea, cranberry, apple, onions, asparagus, radish leaves, buckwheat, blueberry, broccoli, and coriander. It occurs in many different forms, but the most abundant quercetin derivatives are glycosides and ethers, namely, Quercetin 3-O-glycoside, Quercetin 3-sulfate, Quercetin 3-glucuronide, and Quercetin 3'-metylether. Quercetin has antioxidant, anti-inflammatory, cardioprotective, antiviral, and antibacterial effects. It is found to be beneficial against cardiovascular diseases, cancer, diabetes, neuro-degenerative diseases, allergy asthma, peptic ulcers, osteoporosis, arthritis, and eye disorders. In pre-clinical and clinical investigations, its impacts on various signaling pathways and molecular targets have demonstrated favorable benefits for the activities mentioned above, and some global clinical trials have been conducted to validate its therapeutic profile. It is also utilized as a nutraceutical due to its pharmacological properties. Although quercetin has several pharmacological benefits, its clinical use is restricted due to its poor water solubility, substantial first-pass metabolism, and consequent low bioavailability. To circumvent this limited bioavailability, a quercetin-based nanoformulation has been considered in recent times as it manifests increased quercetin uptake by the epithelial system and enhances the delivery of quercetin to the target site. This review mainly focuses on pharmacological action, clinical trials, patents, marketed products, and approaches to improving the bioavailability of quercetin with the use of a nanoformulation.

Pharmacology activity, toxicity, and clinical trials of Erythrina genus plants (Fabaceae): an evidence-based review.

The concept of using plants to alleviate diseases is always challenging. In West Java, Indonesia, a local plant, named dadap serep has been traditionally used to reduce blood glucose, fever, and edema, by pounding the leaves and applying them on the inflamed skin, or boiled and consumed as herbal tea. This plant belongs to the Erythrina genus, which covers approximately 120 species. The scope of this review (1943-2023) is related to the Global Development Goals, in particular Goal 3: Good Health and Wellbeing, by focusing on the pharmacology activity, toxicity, and clinical trials of Erythrina genus plants and their metabolites, e.g., pterocarpans, alkaloids, and flavonoids. Articles were searched on PubMed and ScienceDirect databases, using "Erythrina" AND "pharmacology activity" keywords, and only original articles written in English and open access were included. In vitro and in vivo studies reveal promising results, particularly for antibacterial and anticancer activities. The toxicity and clinical studies of Erythrina genus plants are limitedly reported. Considering that extensive caution should be taken when prescribing botanical drugs for patients parallelly taking a narrow therapeutic window drug, it is confirmed that no interactions of the Erythrina genus were recorded, indicating the safety of the studied plants. We, therefore, concluded that Erythrina genus plants are promising to be further explored for their effects in various signaling pathways as future plant-based drug candidates.

Stroke risk management in carotid atherosclerotic disease: A Clinical Consensus Statement of the ESC Council on Stroke and the ESC Working Group on Aorta and Peripheral Vascular Diseases.

Carotid atherosclerotic disease continues to be an important cause of stroke, often disabling or fatal. Such strokes could be largely prevented through optimal medical therapy and carotid revascularization. Advancements in discovery research and imaging along with evidence from recent pharmacology and interventional clinical trials and registries and the progress in acute stroke management have markedly expanded knowledge base for clinical decisions in carotid stenosis. Nevertheless, there is variability in carotid-related stroke prevention and management strategies across medical specialities. Optimal patient care can be achieved by (1) establishing a unified knowledge foundation and (2) fostering multi-specialty collaborative guidelines. The emergent Neuro-Vascular Team concept, mirroring the multi-disciplinary Heart Team, embraces diverse specializations, tailores personalized, stratified medicine approaches to individual patient needs, and integrates innovative imaging and risk-assessment biomarkers. Proposed approach integrates collaboration of multiple specialists central to carotid artery stenosis management such as neurology, stroke medicine, cardiology, angiology, ophthalmology, vascular surgery, endovascular interventions, neuroradiology and neurosurgery. Moreover, patient education regarding current treatment options, their risks and advantages, is pivotal, promting patient's active role in clinical care decisions. This enables optimization of interventions ranging from lifestyle modification, carotid revascularization by stenting or endarterectomy, as well as pharmacological management encompassing statins, novel lipid-lowering and antithrombotic strategies and targeting inflammation and vascular dysfunction. This consensus document provides a harmonized multi-specialty approach to multimorbidity prevention in carotid stenosis patients, based on comprehensive knowledge review, pinpointing research gaps in an evidence-based medicine approach. It aims to be a foundational tool for interdisciplinary collaboration and prioritized patient-centric decision-making.

Impact of seed amplification assay and surface-enhanced Raman spectroscopy combined approach on the clinical diagnosis of Alzheimer’s disease

BackgroundThe current diagnosis of Alzheimer’s disease (AD) is based on a series of analyses which involve clinical, instrumental and laboratory findings. However, signs, symptoms and biomarker alterations observed in AD might overlap with other dementias, resulting in misdiagnosis.MethodsHere we describe a new diagnostic approach for AD which takes advantage of the boosted sensitivity in biomolecular detection, as allowed by seed amplification assay (SAA), combined with the unique specificity in biomolecular recognition, as provided by surface-enhanced Raman spectroscopy (SERS).ResultsThe SAA-SERS approach supported by machine learning data analysis allowed efficient identification of pathological Aβ oligomers in the cerebrospinal fluid of patients with a clinical diagnosis of AD or mild cognitive impairment due to AD.ConclusionsSuch analytical approach can be used to recognize disease features, thus allowing early stratification and selection of patients, which is fundamental in clinical treatments and pharmacological trials.

Dynorphin 1-17 biotransformation peptides: properties, challenges and solutions for future therapeutics development.

It is well established that endogenously produced dynorphin 1-17 (DYN 1-17) is susceptible to enzymatic degradation, producing a variety of unique fragments in different tissue matrices and disease pathologies. DYN 1-17 and its major biotransformation fragments have significant roles in neurological and inflammatory disorders upon interacting with opioid and non-opioid receptors at both central and peripheral levels, thus highlighting their potential as drug candidates. Nevertheless, their development as promising therapeutics is challenged by several issues. This review aims to provide the latest and comprehensive updates on DYN 1-17 biotransformed peptides, including their pharmacological roles, pharmacokinetic studies and relevant clinical trials. Challenges in their development as potential therapeutics and proposed solutions to overcome these limitations are also discussed.

Tapentadol: A Review of Experimental Pharmacology Studies, Clinical Trials, and Recent Findings.

Tapentadol is an analgesic compound that acts centrally to attenuate pain. Previous studies have shown that tapentadol has dual mechanisms of action as a mu-opioid receptor agonist and noradrenaline re-uptake inhibition. Therefore, tapentadol provides a great advantage over classic opioids in pain management from nociceptive to neuropathic. Cumulative evidence from in vitro data suggests that tapentadol effect of norepinephrine re-uptake could be a new target that overcomes other classic opioids in chronic neuropathic pain. Compared to tramadol and other opioids, tapentadol is associated with fewer adverse effects than tramadol. Tapentadol is a new alternative to treat acute, chronic, and neuropathic pain. Thus, this review article was focused on understanding the studies that led to the development of tapentadol as a novel analgesic drug and its advantages over conventional opioids. Thus, tapentadol is a good alternative with fewer adverse effects and is available for human use.

Новое в лечении сердечной недостаточности: верицигуат

The author reviews the pharmacological properties and clinical trials of vericiguate, a stimulant of soluble guanylate cyclase, that is intended for use in patients with chronic heart failure. The new medicine alleviates unfavorable effects of endothelial dysfunction and other disorders associated with a deficiency of bioavailable nitric oxide and suppressed activity of soluble guanylate cyclase. The efficacy of vericiguate in chronic heart failure with a reduced ejection fraction was established in clinical trials SOCRATES-REDUCED and VICTORIA.

International Consensus of Continuous Glucose Monitor Use in Pharmacological Clinical Trials in Diabetes.

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Current comprehensive understanding of denosumab (the RANKL neutralizing antibody) in the treatment of bone metastasis of malignant tumors, including pharmacological mechanism and clinical trials.

Denosumab, a fully humanized monoclonal neutralizing antibody, inhibits activation of the RANK/RANKL/OPG signaling pathway through competitive binding with RANKL, thereby inhibiting osteoclast-mediated bone resorption. Denosumab inhibits bone loss; therefore, it is used to treat metabolic bone diseases (including postmenopausal osteoporosis, male osteoporosis, and glucocorticoid-induced osteoporosis), in clinical practice. Since then, multiple effects of denosumab have been discovered. A growing body of evidence suggests that denosumab has a variety of pharmacological activities and broad potential in clinical diseases such as osteoarthritis, bone tumors, and other autoimmune diseases. Currently, Denosumab is emerging as a treatment for patients with malignancy bone metastases, and it also shows direct or indirect anti-tumor effects in preclinical models and clinical applications. However, as an innovative drug, its clinical use for bone metastasis of malignant tumors is still insufficient, and its mechanism of action needs to be further investigated. This review systematically summarizes the pharmacological mechanism of action of denosumab and the current understanding and clinical practice of the use of denosumab for bone metastasis of malignant tumors to help clinicians and researchers deepen their understanding of denosumab.

Major benznidazole metabolites in patients treated for Chagas disease: Mass spectrometry-based identification, structural analysis and detoxification pathways

Benznidazole is the drug of choice for the treatment of Chagas disease, but its metabolism in humans is unclear. Here, we identified and characterized the major benznidazole metabolites and their biosynthetic mechanisms in humans by analyzing the ionic profiles of urine samples from patients and untreated donors through reversed-phase UHPLC-ESI-QTOF-MS and UHPLC-ESI-QqLIT-MS. A strategy for simultaneous detection and fragmentation of characteristic positive and negative ions was employed using information-dependent acquisitions (IDA). Selected precursor ions, neutral losses, and MS3 experiments complemented the study. A total of six phase-I and ten phase-II metabolites were identified and structurally characterized in urine of benznidazole-treated patients. Based on creatinine-corrected ion intensities, nitroreduction to amino-benznidazole (M1) and its subsequent N-glucuronidation to M5 were the main metabolic pathways, followed by imidazole-ring cleavage, oxidations, and cysteine conjugations. This extensive exploration of benznidazole metabolites revealed potentially toxic structures in the form of glucuronides and glutathione derivatives, which may be associated with recurrent treatment adverse events; this possibility warrants further exploration in future clinical trials. Incorporation of this knowledge of the benznidazole metabolic profile into clinical pharmacology trials could lead to improved treatments, facilitate the study of possible drug-drug interactions, and even mitigation of adverse drug reactions.

Pharmacokinetic comparability between two populations using nonlinear mixed effect models: a Monte Carlo study.

'Are two populations the same or are they different' is a question that is often faced in clinical pharmacology trials e.g., a pharmacokinetic trial studying a particular drug in racially different groups. To address this question, concentration-time data were simulated from a reference and test population, where in the latter the clearance, sample size, and sampling design were systematically varied. It was of interest to determine whether the estimates of clearance from the two groups were the same or different. Two approaches were used to estimate the empirical Bayes estimates (EBEs) for clearance. One approach developed a population pharmacokinetic model for the reference population and the EBEs for the reference population were estimated from this model. The parameters of the reference population were fixed to their maximum likelihood estimates. The model was then applied to the test population dataset to estimate the EBEs of the test population using the MAXEVAL = 0 option in NONMEM. A second approach, the theta approach, combined the reference and test datasets into a single dataset and used population as a covariate in the model; the EBEs were estimated from this combined model. The power and type I error rate of each approach were calculated for each treatment combination using a variety of statistical tests to determine whether there was a difference in the distribution of the EBEs in the reference population compared to the test population. Our results suggest that either MAXEVAL or theta approaches can be used with informative sampling designs. In addition to reasonable power and type I error, both approaches gave almost identical results under a dense sampling design. To statistically compare the distribution of EBEs of pharmacokinetic parameters from a reference group to that of a test group, a T-test and DTS eCDF test are equally useful.

Real-world effect of a potential drug-drug interaction between topiramate and oral contraceptives on unintended pregnancy outcomes

ObjectiveTo evaluate the association of concomitant topiramate and oral hormonal contraceptive use with unintended pregnancies. Study DesignWe conducted a retrospective cohort design in MarketScan Research Databases (2005−2018) on women aged 12−48 who had migraines or chronic headaches and concomitantly used topiramate and oral contraceptives. We used a cohort of patients with oral contraceptives and concomitant use of other migraine prevention therapies (propranolol, metoprolol, amitriptyline, venlafaxine, or verapamil) as a comparator. We followed patients for up to 1 year from cohort entry to assess the occurrence of unintended pregnancy (i.e., contraception failure). Pregnancy events were measured via an algorithm harnessing medical encounters information with live births, terminations, or prenatal visits. Statistical models accounted for multiple cohort entries and adjusted for measured confounders via a propensity score weighting method. ResultsWe identified 63,649 episodes of oral contraceptives+topiramateand 59,012 episodes of oral contraceptives+other maintenance therapies. The mean age was 29.2±9.0 and 29.0±9.3 years in the study cohorts. In the adjusted analysis, the contraception failure rate (95% confidence interval) was 1.3 (1.1, 1.6) per 100 person-years in the oral contraceptives+topiramate cohort and 1.3 (1.1, 1.6) in the oral contraceptives+other maintenance therapies cohort. The adjusted rate ratio and rate difference measures were 1.00 (0.80, 1.26) and 0.00 (-0.3, 0.3). ConclusionConcomitant use of low-dose topiramate and oral contraceptives among patients with migraines was not associated with a higher risk for unintended pregnancies. ImplicationsOur real-world findings confirm clinical pharmacology trials, suggesting that low-dose (≤200 mg/d) topiramate may not influence oral contraceptive effectiveness.