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Epilepsia Feb 2020To determine the incidence of hyperlipidemia after first anticonvulsant treatment for seizures, using a large US administrative claims database.
OBJECTIVE
To determine the incidence of hyperlipidemia after first anticonvulsant treatment for seizures, using a large US administrative claims database.
METHODS
We obtained data from the MarketScan Commercial and Medicare databases for 2005-2009 for all adult patients newly treated with an anticonvulsant for seizures who had no previous history of hyperlipidemia or treatment with a lipid-lowering agent. We divided the population based upon whether they were treated with an enzyme-inducing anticonvulsant (phenytoin, carbamazepine, phenobarbital, primidone) or a noninducing anticonvulsant (all others). The primary outcome measure was a new diagnosis of hyperlipidemia during subsequent follow-up. We accounted for a large number of demographic and clinical covariates.
RESULTS
Of 11 374 subjects, 8778 (77%) were prescribed noninducers and 2596 (23%) were prescribed inducers. New hyperlipidemia diagnoses were seen in 14.6% of the patients started on inducing anticonvulsants and 10.7% of the patients started on noninducing anticonvulsants (P < .001). Both hyperlipidemia and the use of inducers were significantly associated with older age and male gender. After accounting for covariates, inducer prescription was still associated with 23% higher odds of a subsequent diagnosis of hyperlipidemia (odds ratio = 1.225, 95% confidence interval = 1.066-1.408, P < .001).
SIGNIFICANCE
The use of enzyme-inducing anticonvulsants in patients with newly diagnosed epilepsy was associated with a significant increase in subsequent diagnoses of hyperlipidemia, suggesting that the lipid-elevating properties of these agents are of genuine clinical importance. This adds to the body of data demonstrating that these agents are likely associated with additional hassle, cost, and morbidity.
Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anticonvulsants; Databases, Factual; Epilepsy; Female; Humans; Hyperlipidemias; Hypolipidemic Agents; Incidence; Male; Medicare; Middle Aged; Population; Seizures; Sex Factors; Socioeconomic Factors; Treatment Outcome; United States; Young Adult
PubMed: 31912492
DOI: 10.1111/epi.16420 -
International Review of Neurobiology 2022γ-Aminobutyric acid (GABA) is the most prevalent inhibitory CNS neurotransmitter. Activating GABA-A receptors hyperpolarizes cells via Cl influx, which inhibits action...
γ-Aminobutyric acid (GABA) is the most prevalent inhibitory CNS neurotransmitter. Activating GABA-A receptors hyperpolarizes cells via Cl influx, which inhibits action potentials. Although the exact pathophysiologies of tremor are incompletely understood, proposed neuroanatomy extensively implicates GABA pathways. Pathological studies and imaging studies also show GABA abnormalities in patients with ET. Most importantly, medications that activate GABA-A receptors, such as primidone, often improve tremor. Ongoing clinical trials and physiology research should further refine potential future GABAergic targets and treatments, which are currently the most promising targets for pharmacological intervention.
Topics: Essential Tremor; Humans; Receptors, GABA; Receptors, GABA-A; Tremor; gamma-Aminobutyric Acid
PubMed: 35750368
DOI: 10.1016/bs.irn.2022.02.007 -
Epilepsy Research Jul 2024Pharmacovigilance systems such as the FDA Adverse Event Reporting System (FAERS), are established models for adverse event surveillance that may have been missed during...
BACKGROUND
Pharmacovigilance systems such as the FDA Adverse Event Reporting System (FAERS), are established models for adverse event surveillance that may have been missed during clinical trials. We aimed to analyze twenty-five anti-seizure medications (ASMs) in FAERS to assess for increased reporting of suicidal and self-injurious behavior.
METHODS
Twenty-five ASMs were analyzed: brivaracetam, cannabidiol, carbamazepine, clobazam, clonazepam, diazepam, eslicarbazepine, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, phenobarbital, phenytoin, pregabalin, primidone, rufinamide, stiripentol, tiagabine, topiramate, valproate, vigabatrin, zonisamide. Reports of "suicidal and self-injurious behavior" were collected from January 1, 2004, to December 31, 2020, using OpenVigil 2.1 tool with indication as "Epilepsy". Relative reporting ratio, proportional reporting ratio, and reporting odds ratio were calculated utilizing all other drug reports for epilepsy patients as a control.
RESULTS
Significant relative operating ratio, ROR (greater than 1, p<0.05) were observed for diazepam (2.909), pregabalin (2.739), brivaracetam (2.462), gabapentin (2.185), clonazepam (1.649), zonisamide (1.462), lacosamide (1.333), and levetiracetam (1.286).
CONCLUSIONS
Of the 25 ASMs that were analyzed in this study, 4 (16%) were identified to have been linked with a likely true adverse event. These drugs included diazepam, brivaracetam, gabapenetin, and pregabalin. Although several limitations are present with the FAERS database, it is imperative to closely monitor patient comorbidities for increased risk of suicidality with the use of several ASMs.
Topics: Humans; Anticonvulsants; Self-Injurious Behavior; United States; United States Food and Drug Administration; Male; Female; Adverse Drug Reaction Reporting Systems; Adult; Adolescent; Middle Aged; Suicide; Young Adult; Databases, Factual; Pharmacovigilance; Child; Aged
PubMed: 38761467
DOI: 10.1016/j.eplepsyres.2024.107382 -
Neurologia I Neurochirurgia Polska 2020Tremor is one of the most common movement disorders. It does not usually respond to first-line drug treatments (e.g. propranolol, primidone, anticholinergics, gabapentin... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tremor is one of the most common movement disorders. It does not usually respond to first-line drug treatments (e.g. propranolol, primidone, anticholinergics, gabapentin and clonazepam) due to side effects and frequent dose limitations. Botulinum toxin type A (BoNT-A) has been widely used to treat tremor, but its efficacy and safety are uncertain.
AIMS
To evaluate the efficacy and safety of BoNT-A in the treatment of hand tremor.
METHODS
We searched the MEDLINE, EMBASE, PsycINFO and Cochrane Library databases for relevant randomised controlled trials of the effects of BoNT-A injections on tremors, up to 20 February 2020. A meta-analysis of comparative effects was performed using R studio software, and publication bias was examined using Egger's test.
RESULTS
Six studies examining a total of 245 participants with tremor were included in the meta-analysis. The primary outcome of meta-analysis showed no difference in clinical tremor scale scores between the BoNT-A group versus the placebo group (standardised mean difference (SMD): -0.42, 95% confidence interval (CI): -1.94 to 1.10; I2 = 96%). For clinical tremor scale scores, subgroup analyses suggested that the BoNT-A group may differ in terms of multiple sclerosis (MS) related tremor (SMD: -1.10; 95% CI: -2.17 to -0.04; I2 = 79%) compared to a placebo, but the difference did not exist in the outcome of essential tremor (ET) or hand tremor (MD: -1.31; 95% CI: -3.39; 1.31; I2 = 97%). Grip strength (MD: -1.25, 95% CI: -5.99 to 3.50, I2 = 97%) was slightly lower in the BoNT-A group, but the difference was not significant. The incidence of adverse events (AEs), including hand weakness (RR: 2.96, 95% CI: 1.40 to 6.24, I2 = 37%), was significantly greater in the BoNT-A group than in the placebo group. Two studies were assessed as having an overall low risk of bias.
CONCLUSIONS
Our study confirms that BoNT-A injections are unlikely to have an impact on patients with hand tremors. However, subgroup analysis suggested that BoNT-A injections could have possible benefits in MS-related tremor. While moderate to severe hand weakness AEs often limits their use in clinical practice, additional well-designed double-blind, placebo-controlled trials are needed to provide more robust conclusions.
Topics: Botulinum Toxins, Type A; Hand; Humans; Muscle Weakness; Tremor
PubMed: 33047784
DOI: 10.5603/PJNNS.a2020.0079 -
Epilepsia May 2020The aim of this study was to investigate the influence of concomitant antiepileptic drugs (AEDs) on brivaracetam (BRV) trough serum concentrations. A total number of 368...
The aim of this study was to investigate the influence of concomitant antiepileptic drugs (AEDs) on brivaracetam (BRV) trough serum concentrations. A total number of 368 routinely collected blood samples from 148 inpatients from Mara Hospital (Bethel Epilepsy Center) and von Bodelschwingh Foundation Bethel were retrospectively evaluated. Generalized estimation equations (GEEs) were used for statistical analysis. GEE analyses showed that BRV trough serum concentrations were significantly lower in patients with strong enzyme-inducing AEDs (carbamazepine, phenytoin, and/or phenobarbital/primidone, -49%), but were not affected by concomitant intake of oxcarbazepine or eslicarbazepine. Age and gender did not have a significant effect. An alternative GEE model analyzing the BRV level-to-dose ratios yielded comparable results. Our results from routine therapeutic drug monitoring data indicate that the effect of enzyme-inducing AEDs on BRV serum concentrations is stronger than the 20%-30% reduction in BRV exposure previously reported in pharmacokinetics studies. Further research is necessary to evaluate these differences and to elucidate possible clinical consequences.
Topics: Adolescent; Adult; Aged; Anticonvulsants; Carbamazepine; Child; Dibenzazepines; Drug Interactions; Drug Therapy, Combination; Epilepsy; Female; Humans; Male; Middle Aged; Oxcarbazepine; Phenobarbital; Phenytoin; Pyrrolidinones; Retrospective Studies; Young Adult
PubMed: 32304097
DOI: 10.1111/epi.16500 -
Therapeutic Drug Monitoring Apr 2022Therapeutic drug monitoring (TDM) of antiseizure medications (ASMs) is widely used to guide therapy, avoid toxicity, and assess patient compliance. Commercial...
Simultaneous Quantification of 11 Antiseizure Medications and Metabolites in Serum for Therapeutic Drug Monitoring Using High-Performance Liquid Chromatography with Ultraviolet Detection: A Short Communication.
BACKGROUND
Therapeutic drug monitoring (TDM) of antiseizure medications (ASMs) is widely used to guide therapy, avoid toxicity, and assess patient compliance. Commercial immunologic quantification methods are common practice; however, as they are only applicable to one specific drug and prone to cross-reacting metabolites, their practical applicability is limited. In this article, the authors proposed a high-performance liquid chromatography method using ultraviolet detection (HPLC-UV) for simultaneous quantification of 11 ASMs and active metabolites (carbamazepine, felbamate, lacosamide, lamotrigine, levetiracetam, phenobarbital, phenytoin, primidone, zonisamide, carbamazepine-10,11-epoxide, and licarbazepine) in serum.
METHODS
Chromatographic separation was performed on a Phenomenex Luna PFP(2) (3-µm particle size; 150 × 4.6 mm i.d.) analytical column. The mobile phase comprised phosphate buffer (20 mM; pH 3), acetonitrile (ACN), and methanol using gradient elution. Analyses were conducted at 35°C and a 1.3-mL/min flow rate. The detection wavelength for all analytes was 210 nm. The samples were prepared by protein precipitation using ACN.
RESULTS
The HPLC-UV method was validated according to the FDA guidelines and applied to measure patient samples in TDM. Calibration curves showed excellent linearity (r2 > 0.99) and covered the entire reference range for each analyte. Intraday and interday imprecisions and inaccuracies were <10% for all samples. Extensive stability testing showed no significant degradation (<15%), and interference measurements additionally ensured clinical applicability. Furthermore, the sensitivity was comparable with that of previously published HPLC methods using mass spectrometry.
CONCLUSIONS
The authors developed an HPLC-UV method for the simultaneous quantification of 11 ASMs in the human serum and demonstrated its practical applicability in TDM. The method requires only standard laboratory equipment and simple sample preparation, making TDM available in less specialized laboratories.
Topics: Anticonvulsants; Carbamazepine; Chromatography, High Pressure Liquid; Drug Monitoring; Humans; Phenytoin
PubMed: 35292610
DOI: 10.1097/FTD.0000000000000908 -
Clinical Chemistry and Laboratory... Jun 2024Primidone is an anticonvulsive drug used in the treatment of epilepsy and essential tremor. It offers beneficial effects in controlling seizures, but its usage is...
An isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS)-based candidate reference measurement procedure (RMP) for the quantification of primidone in human serum and plasma.
OBJECTIVES
Primidone is an anticonvulsive drug used in the treatment of epilepsy and essential tremor. It offers beneficial effects in controlling seizures, but its usage is also associated with possible side effects. To ensure optimal therapy, it is crucial to measure its concentration through accurate quantification methods. Therefore, our main goal was to develop and validate a new reference measurement procedure (RMP) for accurately measuring primidone levels in human serum and plasma.
METHODS
In our study, we focused on the separation of primidone from both known and unknown interferences using a C18 column. To achieve accurate sample preparation, we developed a protocol involving protein precipitation followed by a high dilution step. The validation of the assay and determination of measurement uncertainty were carried out following guidelines from organizations such as the Clinical and Laboratory Standards Institute, the International Conference on Harmonization, and the Guide to the Expression of Uncertainty in Measurement. These rigorous validation processes ensure the reliability and accuracy of our method for quantifying primidone levels in human serum and plasma samples.
RESULTS
The RMP was shown to be highly selective and specific, with no evidence of matrix interference. It can be used to quantify primidone in the range of 0.150-30.0 μg/mL. Intermediate precision was less than 4.0 %, and repeatability CV ranged from 1.0 to 3.3 % across all concentration levels. The relative mean bias ranged from 0.1 to 3.9 % for native serum levels, and from -2.6 to 2.8 % for lithium-heparin plasma levels. The measurement uncertainties for single measurements and target value assignment were 1.5-4.1 % and 0.9-1.0 %, respectively.
CONCLUSIONS
In this study, we introduce an innovative LC-MS/MS-based candidate RMP specifically designed for primidone in human serum and plasma. Our RMP offers a traceable platform, facilitating the standardization of routine assays and enabling the evaluation of clinically relevant samples. With this novel approach, we aim to enhance the accuracy and reliability of primidone measurements, ultimately benefiting the field of clinical research and patient care.
Topics: Humans; Tandem Mass Spectrometry; Primidone; Chromatography, Liquid; Reference Standards; Reproducibility of Results; Indicator Dilution Techniques; Limit of Detection; Anticonvulsants; Liquid Chromatography-Mass Spectrometry
PubMed: 38549258
DOI: 10.1515/cclm-2023-1032 -
The Neurologist Sep 2019Dupuytren, Ledderhose, and Peyronie diseases are chronic fibrotic conditions related to progressive fibrosis of the palmar fascia, plantar fascia, and tunica albuginea,...
INTRODUCTION
Dupuytren, Ledderhose, and Peyronie diseases are chronic fibrotic conditions related to progressive fibrosis of the palmar fascia, plantar fascia, and tunica albuginea, respectively. These conditions have been associated with antiepileptic drug use, mainly phenobarbital and primidone.
CASE REPORT
A 71-year-old man developed simultaneous Dupuytren, Ledderhose, and Peyronie diseases after primidone use for essential tremor.
CONCLUSIONS
There are a few reports associating barbiturate use to connective tissue disorders, and some suggest that drug withdrawal may result in a better prognosis. Therefore, physicians must be aware of such adverse events when caring for patients on long-term barbiturate use.
Topics: Aged; Anticonvulsants; Dupuytren Contracture; Essential Tremor; Fibromatosis, Plantar; Humans; Male; Penile Induration; Primidone
PubMed: 31478998
DOI: 10.1097/NRL.0000000000000240 -
BMJ Open Jan 2020Essential tremor (ET), a tremor disorder, is one of the most common movement disorders. Only oral drugs (propranolol, primidone, topiramate, etc)are still the...
INTRODUCTION
Essential tremor (ET), a tremor disorder, is one of the most common movement disorders. Only oral drugs (propranolol, primidone, topiramate, etc)are still the first-line treatment recommended by the Food and Drug Administration. Propranolol is thought to potentially reduce upper limb action tremor. However, it has a poor effect on axial tremor symptoms, such as essential head tremor and voice tremor. Studies have shown that tremor severity develops over time, possibly producing other clinical tremors and neurological soft signs (such as memory loss, gait abnormalities, balance disorders, etc), which further increases the difficulty of treating tremors. However, some recent studies provide emerging evidence for oral propranolol on subgroups of ET, which is based on the anatomical distribution of ET (lower extremities, head, sound, tongue, etc). This systematic review aims to synthesise these new data to improve the efficacy of propranolol in ET subgroups.
METHODS AND ANALYSIS
We will search for randomised controlled trials from the PubMed, MEDLINE, EMBASE, Cochrane Library, UptoDate and PEDro databases from inception to June 2019. All data will be extracted independently by two reviewers and compared at the end of the review. The two reviewers will screen the study quality, and the Cochrane Collaboration's tool in Review Manager (RevMan) V.5.3.3 will be used to evaluate risk of bias. Our primary outcome will be the functional disability component related to tremors, as measured by the Fahn-Tolosa-Marin Tremor Rating Scale subscales B and C. Secondary outcomes will include severity of tremors and quality of life. Narrative and meta-analytical syntheses are planned.
ETHICS AND DISSEMINATION
Published aggregated data will be used in this review analysis and therefore no ethical approval is required. The results will be published in peer-reviewed journals, and proliferation activities will include diverse social stakeholders, non-academic groups and patients.
PROSPERO REGISTRATION NUMBER
CRD42018112580.
Topics: Humans; Administration, Oral; Adrenergic beta-Antagonists; Essential Tremor; Gait; Propranolol; Quality of Life; Treatment Outcome; Meta-Analysis as Topic; Systematic Reviews as Topic
PubMed: 31948986
DOI: 10.1136/bmjopen-2019-032096 -
American Journal of Health-system... Jul 2022We report a unique case of transiently elevated liver function test (LFT) values associated with concurrent use of dabigatran and primidone, which has not previously...
PURPOSE
We report a unique case of transiently elevated liver function test (LFT) values associated with concurrent use of dabigatran and primidone, which has not previously been described in the scientific literature.
SUMMARY
Management of drug-drug interactions requires a fundamental understanding of pharmacodynamic and pharmacokinetic parameters. Despite the use of available best predictive models, idiosyncratic drug reactions may still occur when a newly approved medication begins to be used in the general population. We report a case of a possible interaction (Naranjo adverse drug reaction probability score of 3, Roussel Uclaf causality assessment method score of 3) between dabigatran and primidone in a 70-year-old Caucasian male resulting in a transient elevation of LFT values. The patient was transitioned from warfarin to dabigatran in the setting of persistently subtherapeutic international normalized ratio values. During a routine outpatient follow-up appointment approximately 1 month after dabigatran initiation, the patient was discovered to have LFT values greater than 5 times the upper limit of normal. Dabigatran was thus discontinued; the patient was returned to warfarin therapy and their LFT values returned to baseline.
CONCLUSION
Studies have indicated a potential for reduced dabigatran efficacy with concurrent use of primidone due to P-glycoprotein induction, thereby potentiating the risk for thrombosis. To date, reports of this interaction resulting in hepatic injury are lacking. The present case suggests that this interaction may be clinically significant with regard to selection of antithrombotic medication therapy in patients on primidone therapy.
Topics: Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; International Normalized Ratio; Liver Function Tests; Male; Primidone; Warfarin
PubMed: 35212353
DOI: 10.1093/ajhp/zxac054