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Ornello R, Caponnetto V, Ahmed F, Al-Khazali HM, Ambrosini A, Ashina S, Baraldi C, Bellotti A, Brighina F, Calabresi P, Casillo F, Cevoli S, Cheng S, Chiang CC, Chiarugi A, Christensen RH, Chu MK, Coppola G, Corbelli I, Crema S, De Icco R, de Tommaso M, Di Lorenzo C, Di Stefano V, Diener HC, Ekizoğlu E, Fallacara A, Favoni V, Garces KN, Geppetti P, Goicochea MT, Granato A, Granella F, Guerzoni S, Ha WS, Hassan A, Hirata K, Hoffmann J, Hüssler EM, Hussein M, Iannone LF, Jenkins B, Labastida-Ramirez A, Laporta A, Levin M, Lupica A, Mampreso E, Martinelli D, Monteith TS, Orologio I, Özge A, Pan LLH, Panneerchelvam LL, Peres MFP, Souza MNP, Pozo-Rosich P, Prudenzano MP, Quattrocchi S, Rainero I, Romanenko V, Romozzi M, Russo A, Sances G, Sarchielli P, Schwedt TJ, Silvestro M, Swerts DB, Tassorelli C, Tessitore A, Togha M, Vaghi G, Wang SJ, Ashina M, Sacco S. Evidence-based guidelines for the pharmacological treatment of migraine. Cephalalgia 2025; 45:3331024241305381. [PMID: 40277319 DOI: 10.1177/03331024241305381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/26/2025]
Abstract
We here present evidence-based guidelines for the pharmacological treatment of migraine. These guidelines, created by the Italian Society for the Study of Headache and the International Headache Society, aim to offer clear, actionable recommendations to healthcare professionals. They incorporate evidence-based recommendations from randomized controlled trials and expert-based opinions. The guidelines follow the Grading of Recommendations, Assessment, Development and Evaluation approach for assessing the quality of evidence. The guideline development involved a systematic review of literature across multiple databases, adherence to Cochrane review methods, and a structured framework for data extraction and interpretation. Although the guidelines provide a robust foundation for migraine treatment, they also highlight gaps in current research, such as the paucity of head-to-head drug comparisons and the need for long-term outcome studies. These guidelines serve as a resource to standardize migraine treatment and promote high-quality care across different healthcare settings.
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Affiliation(s)
- Raffaele Ornello
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Valeria Caponnetto
- Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
| | - Fayyaz Ahmed
- Hull University Teaching Hospitals NHS Trust., Hull, UK
| | - Haidar M Al-Khazali
- Department of Neurology, Danish Headache Center, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | | | - Sait Ashina
- Department of Neurology and Department of Anesthesia, Critical Care and Pain Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Carlo Baraldi
- Digital and Predictive Medicine, Pharmacology and Clinical Metabolic Toxicology -Headache Center and Drug Abuse - Laboratory of Clinical Pharmacology and Pharmacogenomics, AOU of Modena, Modena, Italy
| | - Alessia Bellotti
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Filippo Brighina
- Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, Palermo Italy
| | - Paolo Calabresi
- Dipartimento di Neuroscienze, Organi di Senso e Torace, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Dipartimento di Neuroscienze, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Francesco Casillo
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino - ICOT - Latina, Italy
| | - Sabina Cevoli
- IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma Cefalee e Algie Facciali, Bologna, Italy
| | - Shuli Cheng
- Department of Neurology, Alfred Health, Melbourne, Victoria, Australia
| | | | - Alberto Chiarugi
- Department of Health Sciences - Section of Clinical Pharmacology and Oncology - Headache Center, Careggi University Hospital - University of Florence, Italy
| | - Rune Häckert Christensen
- Department of Neurology, Danish Headache Center, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Min Kyung Chu
- Department of Neurology, Severance Hospital, Yonsei University, Republic of Korea
| | - Gianluca Coppola
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino - ICOT - Latina, Italy
| | - Ilenia Corbelli
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Santiago Crema
- Headache Clinic, Neurology Department, Fleni, Buenos Aires, Argentina
| | - Roberto De Icco
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
- Headache Science and Neurorehabilitation Unit, IRCSS Mondino Foundation, Pavia, Italy
| | - Marina de Tommaso
- DiBrain Department, Neurophysiopathology Unit, Bari Aldo Moro University, Bari, Italy
| | - Cherubino Di Lorenzo
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino - ICOT - Latina, Italy
| | - Vincenzo Di Stefano
- Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, Palermo Italy
| | - Hans-Christoph Diener
- Department of Neuroepidemiology, Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), Faculty of Medicine, University Duisburg-Essen, Essen, Germany
| | - Esme Ekizoğlu
- Istanbul Faculty of Medicine, Department of Neurology, Istanbul University, Istanbul, Turkey
| | - Adriana Fallacara
- Headache Center, Amaducci Neurological Clinic, Polyclinic Hospital-University Consortium Bari, Italy
| | - Valentina Favoni
- IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma Cefalee e Algie Facciali, Bologna, Italy
| | - Kimberly N Garces
- Department of Neurology-Headache Division, University of Miami, Miller School of Medicine, Miami, USA
| | - Pierangelo Geppetti
- Department of Health Sciences - Section of Clinical Pharmacology and Oncology - Headache Center, Careggi University Hospital - University of Florence, Italy
- Department of Molecular Pathobiology and Pain Research Center, College of Dentistry, New York University, New York, USA
| | | | - Antonio Granato
- Clinical Unit of Neurology, Headache Center, Department of Medical, Surgical and Health Sciences, University Hospital and Health Services of Trieste, ASUGI, University of Trieste, Trieste, Italy
| | - Franco Granella
- Unit of Neurosciences, Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Simona Guerzoni
- Digital and Predictive Medicine, Pharmacology and Clinical Metabolic Toxicology -Headache Center and Drug Abuse - Laboratory of Clinical Pharmacology and Pharmacogenomics, AOU of Modena, Modena, Italy
| | - Woo-Seok Ha
- Department of Neurology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Amr Hassan
- Department of Neurology, Kasr Al Ainy Hospitals, Faculty of Medicine, Cairo University, Egypt
| | | | - Jan Hoffmann
- Wolfson Sensory, Pain and Regeneration Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
| | - Eva-Maria Hüssler
- Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, Essen, Germany
| | - Mona Hussein
- Department of Neurology, Beni-Suef University, Beni-Suef, Egypt
| | - Luigi Francesco Iannone
- Department of Health Sciences - Section of Clinical Pharmacology and Oncology - Headache Center, Careggi University Hospital - University of Florence, Italy
| | | | - Alejandro Labastida-Ramirez
- Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester; Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Northern Care Alliance NHS Foundation Trust, University of Manchester, Manchester, UK
| | - Anna Laporta
- DiBrain Department, Neurophysiopathology Unit, Bari Aldo Moro University, Bari, Italy
| | - Morris Levin
- Headache Center, University of California, San Francisco, CA, USA
| | - Antonino Lupica
- Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, Palermo Italy
| | | | - Daniele Martinelli
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
| | - Teshamae S Monteith
- Headache Center, Amaducci Neurological Clinic, Polyclinic Hospital-University Consortium Bari, Italy
| | - Ilaria Orologio
- Headache Centre of Department of Advanced Medical and Surgical Sciences University of Campania "Luigi Vanvitelli" Naples, Italy
| | - Aynur Özge
- Department of Neurology, Mersin University Medical School, Mersin, Turkey
| | | | | | - Mario F P Peres
- Department of Neurology, Hospital Israelita Albert Einstein, Sao Paulo, Brazil
| | | | - Patricia Pozo-Rosich
- Headache Clinic, Neurology Department, Vall d'Hebron Hospital, Barcelona, Spain; Headache and Neurological Pain Research Group, VHIR, Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Maria Pia Prudenzano
- Headache Center, Amaducci Neurological Clinic, Polyclinic Hospital-University Consortium Bari, Italy
| | - Silvia Quattrocchi
- IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma Cefalee e Algie Facciali, Bologna, Italy
| | - Innocenzo Rainero
- Headache Center, Department of Neuroscience "Rita Levi Montalcini", University of Torino, Torino, Italy
| | | | - Marina Romozzi
- Dipartimento di Neuroscienze, Organi di Senso e Torace, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Dipartimento di Neuroscienze, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Antonio Russo
- Headache Centre of Department of Advanced Medical and Surgical Sciences University of Campania "Luigi Vanvitelli" Naples, Italy
| | - Grazia Sances
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
| | - Paola Sarchielli
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Todd J Schwedt
- Department of Neurology, Mayo Clinic, Phoenix, Arizona, USA
| | - Marcello Silvestro
- Headache Centre of Department of Advanced Medical and Surgical Sciences University of Campania "Luigi Vanvitelli" Naples, Italy
| | | | - Cristina Tassorelli
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
- Headache Science and Neurorehabilitation Unit, IRCSS Mondino Foundation, Pavia, Italy
| | - Alessandro Tessitore
- Headache Centre of Department of Advanced Medical and Surgical Sciences University of Campania "Luigi Vanvitelli" Naples, Italy
| | - Mansoureh Togha
- Headache Department, Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
- Headache Department, Neurology Ward, Sina Hospital, Medical School, Tehran University of Medical Sciences, Tehran, Iran
| | - Gloria Vaghi
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
- Headache Science and Neurorehabilitation Unit, IRCSS Mondino Foundation, Pavia, Italy
| | - Shuu-Jiun Wang
- Department of Neurology, Taipei Veterans General Hospital, Taipei
- College of Medicine, National Yang Ming Chiao Tung University, Taipei
| | - Messoud Ashina
- Department of Neurology, Danish Headache Center, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
- Department of Neurology, Severance Hospital, Yonsei University, Republic of Korea
| | - Simona Sacco
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
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Li Y, Li M, Wang M, Yao J, Li F, Chen S, Yin X, Gao Z. Multigenetic pharmacogenomics-guided treatment shows greater improvements on motor symptoms compared to usual therapy in Parkinson's disease: a small real-word prospective cohort study. Front Pharmacol 2025; 16:1502379. [PMID: 40201683 PMCID: PMC11975922 DOI: 10.3389/fphar.2025.1502379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Accepted: 03/07/2025] [Indexed: 04/10/2025] Open
Abstract
Background Dopamine replacement therapy is a cornerstone of Parkinson's disease treatment. In clinical practice, there is considerable variability in patients' responses, tolerability, and safety regarding anti-parkinsonian medications, which is largely influenced by genetic polymorphisms in pharmacokinetic and pharmacodynamic genes. However, the application of multigenetic pharmacogenomics-guided treatment (MPGT) to optimize therapeutic outcomes in Parkinson's disease (PD) remains under-explored. In this study, we conducted a prospective cohort investigation to evaluate the potential benefits of MPGT on motor symptoms in PD patients. Methods A total of 28 patients with PD were followed for 4 weeks. Among them, 22 patients underwent multigenetic pharmacogenomic testing, with 13 receiving treatments based on the test results (MPGT group). The remaining 15 received standard care (TAU group). Baseline characteristics, as well as changes in Unified Parkinson's Disease Rating Scale (UPDRS) III scores and sub-scores, were compared between the two groups. Associations between various single nucleotide polymorphisms (SNPs) and treatment outcomes were analyzed using generalized linear models. Results At the 4-week follow-up, the MPGT group showed significantly greater reductions in UPDRS III total scores (p < 0.05) and limb sub-scores (p < 0.01) compared to the TAU group. These differences remained significant after adjusting for increases in levodopa equivalent daily dose (p = 0.011 and p = 0.002, respectively) and piribedil use (p = 0.006 and p = 0.004, respectively). Patients homozygous for the major allele of rs4984241 (AA vs. AG+GG, p = 0.003), rs4680 (GG vs. GA+AA, p = 0.013), rs1076560/rs2283265 (CC vs. AC+AA, p = 0.039) and rs622342 (AA vs. AC, p = 0.043) showed greater improvement in total UPDRS III, postural instability and gait difficulty (PIGD), rigidity and tremor scores, respectively, compared to those carrying at least one minor allele. Conclusion MGPT demonstrates significant potential as a valuable tool for personalized treatment in PD patients. Additionally, we identified several SNPs associated with the responsiveness to chronic administration of multiple anti-parkinsonian drugs. However, to confirm these findings, well-designed studies with larger, well-characterized samples are necessary.
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Affiliation(s)
- Yifan Li
- Geriatric Neurological Department of the Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
| | - Mao Li
- Department of Neurology of the First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Miao Wang
- Geriatric Neurological Department of the Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
| | - Jiarui Yao
- Geriatric Neurological Department of the Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
| | - Fengzhu Li
- Geriatric Neurological Department of the Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
| | - Siyu Chen
- Geriatric Neurological Department of the Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
| | - Xi Yin
- Geriatric Neurological Department of the Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
| | - Zhongbao Gao
- Geriatric Neurological Department of the Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
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Şahin SH, Küçük O, Tütüncüler B. The relationship between anti-seizures medications and metabolic acidosis in craniotomy operations: is topiramate or zonisamide the cause of metabolic acidosis? BMC Anesthesiol 2024; 24:296. [PMID: 39192186 PMCID: PMC11348530 DOI: 10.1186/s12871-024-02677-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2024] [Accepted: 08/08/2024] [Indexed: 08/29/2024] Open
Abstract
BACKGROUND/AIM The most commonly prescribed anti-seizures medications (ASMs) for the treatment of epilepsy are currently topiramate, zonisamide, lacosamide, carbamazepine and levetiracetam. The objective of this study was to examine the correlation between preoperative, intraoperative, and postoperative metabolic acidosis and the use of ASMs prior to craniotomy operations. MATERIALS AND METHODS This retrospective cross-sectional study evaluated patients who underwent intracranial surgery with craniotomy under general anaesthesia between May 2020 and April 2023 and used ASMs. The patients were classified into four groups based on the pharmacological mechanisms of action of the ASMs administered before intracranial surgery (Group-I, zonisamide or topiramate; Group-II, lacosamide; Group-III, carbamazepine; Group-IV, levetiracetam). Metabolic acidosis severity was defined based on base excess (BE) levels: mild (-3 to -5), moderate (-5 to -10), and severe (below - 10). The study investigated the correlation between ASMs and the severity of metabolic acidosis in preoperative, intraoperative, and postoperative blood gas measurements. RESULTS Out of 35 patients, 24 patients underwent intracranial surgery and 11 patients underwent epilepsy surgery. There were statistically significant differences in the severity of metabolic acidosis between preoperative (p < 0.001), intraoperative (p < 0.001) and postoperative (p = 0.01) groups. The preoperative mean BE of group-I was - 4.7, which was statistically lower than that of group-III (p = 0.01) and group-IV (p < 0.001). Intraoperatively and postoperatively, group-I had a mean BE of -7.5 and - 3.2, respectively, which was statistically lower than that of groups II (p = 0.007; p = 0.04), III (p = 0.002; p = 0.03), and IV (p < 0.001; p = 0.009). There was no statistically significant difference in BE between groups II, III and IV at all three time points. Group I had the lowest BE at all three time points. Intraoperative bicarbonate was administered to all patients in group I, whereas no intraoperative bicarbonate was required in the other groups. In group I, 50% of patients required postoperative intensive care. CONCLUSION The use of ASMs in patients undergoing surgery is important in terms of mortality and morbidity. Topirimat and zonisamide are ASMs that can cause preoperative, intraoperative and postoperative metabolic acidosis. Patients receiving topirimat or zonisamide are particularly susceptible to metabolic acidosis. Special care should be taken in the management of anaesthesia in patients receiving these drugs, and monitoring of the perioperative metabolic status is essential.
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Affiliation(s)
- Sevtap H Şahin
- Department of Anesthesiology and Reanimation, Faculty of Medicine, University of Trakya, Merkez, Edirne, Turkey
| | - Onur Küçük
- Department of Anesthesiology and Reanimation, Faculty of Medicine, University of Trakya, Merkez, Edirne, Turkey.
- Department of Anesthesiology and Reanimation, University of Health Sciences, Ankara Atatürk Sanatoryum Training and Research Hospital, Keçiören, Ankara, Turkey.
| | - Banu Tütüncüler
- Department of Neurosurgery, Faculty of Medicine, University of Trakya, Merkez, Edirne, Turkey
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Schierscher T, Salzmann L, Singh N, Wild J, Fischer V, Bauland F, Geistanger A, Risch L, Geletneky C, Seger C, Taibon J. An isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS)-based candidate reference measurement procedure for the quantification of zonisamide in human serum and plasma. Clin Chem Lab Med 2024; 62:1288-1300. [PMID: 38105272 DOI: 10.1515/cclm-2023-0736] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Accepted: 11/03/2023] [Indexed: 12/19/2023]
Abstract
OBJECTIVES To describe and validate an isotope dilution-liquid chromatograph-tandem mass spectrometry (ID-LC-MS/MS) based reference measurement procedure (RMP) for zonisamide to accurately measure serum and plasma concentrations. METHODS Quantitative nuclear magnetic resonance (qNMR) spectroscopy was employed to determine the absolute content of the reference material used in order to establish traceability to SI units. Separation of zonisamide from known or unknown interferences was performed on a C8 column. For sample preparation a protocol based on protein precipitation in combination with a high dilution step was established. Assay validation and determination of measurement uncertainty were performed based on guidelines from the Clinical and Laboratory Standards Institute, the International Conference on Harmonization, and the Guide to the expression of uncertainty in measurement. RESULTS The RMP was proven to be highly selective and specific with no evidence of a matrix effect, allowing for quantification of zonisamide within the range of 1.50-60.0 μg/mL. Intermediate precision was <1.4 % and repeatability CV ranged from 0.7 to 1.2 % over all concentration levels. The relative mean bias ranged from 0.0 to 0.8 % for native serum levels and from 0.2 to 2.0 % for Li-heparin plasma levels. The measurement uncertainties for single measurements and target value assignment ranged from 1.1 to 1.4 % and 0.8-1.0 %, respectively. CONCLUSIONS We present a novel LC-MS/MS-based candidate RMP for zonisamide in human serum and plasma which provides a traceable and reliable platform for the standardization of routine assays and evaluation of clinically relevant samples.
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Affiliation(s)
| | | | | | - Janik Wild
- Dr. Risch Ostschweiz AG, Buchs, Switzerland
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MacMahon T, Kelly YP. Zonisamide-induced distal renal tubular acidosis and critical hypokalaemia. BMJ Case Rep 2023; 16:e254615. [PMID: 37041041 PMCID: PMC10105998 DOI: 10.1136/bcr-2023-254615] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/30/2023] [Indexed: 04/13/2023] Open
Abstract
A woman in her 20s presented with rapidly progressive muscle weakness and a 1-month preceding history of fatigability, nausea and vomiting. She was found to have critical hypokalaemia (K+ 1.8 mmol/L), a prolonged corrected QT interval (581 ms) and a normal anion gap metabolic acidosis (pH 7.15) due to zonisamide-induced distal (type 1) renal tubular acidosis. She was admitted to the intensive care unit for potassium replacement and alkali therapy. Clinical and biochemical improvement ensued, and she was discharged after a 27-day inpatient stay.
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Affiliation(s)
- Thomas MacMahon
- Intensive Care Unit, Tallaght University Hospital, Dublin, Ireland
| | - Yvelynne P Kelly
- Intensive Care Unit, Tallaght University Hospital, Dublin, Ireland
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Naps MS, Leong SH, Hartwell EE, Rentsch CT, Kranzler HR. Effects of topiramate therapy on serum bicarbonate concentration in a sample of 10,279 veterans. Alcohol Clin Exp Res 2023; 47:438-447. [PMID: 36810985 DOI: 10.1111/acer.15011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 12/20/2022] [Accepted: 01/03/2023] [Indexed: 02/24/2023]
Abstract
BACKGROUND Topiramate, which is increasingly being used to treat alcohol use disorder (AUD), is commonly associated with reduced serum bicarbonate concentrations. However, estimates of the prevalence and magnitude of this effect are from small samples and do not address whether topiramate's effects on acid-base balance differ in the presence of an AUD or by topiramate dosage. METHODS Veterans Health Administration electronic health record (EHR) data were used to identify patients with a minimum of 180 days of topiramate prescription for any indication and a propensity score-matched control group. We differentiated patients into two subgroups based on the presence of a diagnosis of AUD in the EHR. Baseline alcohol consumption was determined using Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) scores in the EHR. Analysis also included a three-level measure representing mean daily dosage. The topiramate-associated changes in serum bicarbonate concentration were estimated in difference-in-differences linear regression models. A serum bicarbonate concentration <17 mEq/L was considered to represent possible clinically significant metabolic acidosis. RESULTS The cohort comprised 4287 topiramate-treated patients and 5992 propensity score-matched controls with a mean follow-up period of 417 days. The mean topiramate-associated reductions in serum bicarbonate concentration were <2 mEq/L in the low (≤88.75), medium (>88.75 and ≤141.70), and high (>141.70) mg/day dosage tertiles, irrespective of AUD history. Concentrations <17 mEq/L occurred in 1.1% of topiramate-treated patients and 0.3% of controls and were not associated with alcohol consumption or an AUD diagnosis. CONCLUSIONS The excess prevalence of metabolic acidosis associated with topiramate treatment does not differ with dosage, alcohol consumption, or the presence of an AUD. Baseline and periodic serum bicarbonate concentration measurements are recommended during topiramate therapy. Patients prescribed topiramate should be educated about the symptoms of metabolic acidosis and urged to report their occurrence promptly to a healthcare provider.
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Affiliation(s)
- Michelle S Naps
- Mental Illness Research, Education and Clinical Center, Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA.,School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Shirley H Leong
- Mental Illness Research, Education and Clinical Center, Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA
| | - Emily E Hartwell
- Mental Illness Research, Education and Clinical Center, Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA.,Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Christopher T Rentsch
- VA Connecticut Healthcare System, US Department of Veterans Affairs, West Haven, Connecticut, USA.,Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA.,Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK
| | - Henry R Kranzler
- Mental Illness Research, Education and Clinical Center, Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA.,Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
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Thabit MN, Farouk MM. Topiramate-induced ocular side effects in Egyptian patients, idiosyncratic versus dose-dependent effect, a prospective study. THE EGYPTIAN JOURNAL OF NEUROLOGY, PSYCHIATRY AND NEUROSURGERY 2021. [DOI: 10.1186/s41983-020-00263-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
To test the nature of the ocular side effects induced by topiramate (TPM) whether dose dependent or idiosyncratic, and to test various predictors that might influence the occurrence of those side effects.
Methods
Twenty patients treated with TPM were included in this study. Patients underwent ophthalmic assessment before and after 4 weeks of treatment by stable doses of oral TPM. We examined non-cycloplegic refraction (RF) in diopters, best corrected visual acuity (BCVA), intraocular pressure (IOP) in mmHg, and anterior chamber depth (ACD) in mm.
Results
There were no statistically significant differences between baseline and follow-up assessments in all tested ophthalmological parameters including errors of RF, ACD, IOP, and the BCVA. One case suffered from painful drop of vision in both eyes with elevated IOP and decreased ACD, and evident myopic shift 1 week after treatment with small dose of TPM. There was no significant effect of age, TPM dose, disease, and gender on all tested variables.
Conclusion
TPM can induce idiosyncratic, but not dose dependent, ocular side effects, namely myopic shifts and angle closure glaucoma. Those side effects were not disease, age, or gender dependent. However, ethnicity might play a role in induction of those side effects.
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Mahmoud SH, Zhou XY, Ahmed SN. Managing the patient with epilepsy and renal impairment. Seizure 2020; 76:143-152. [PMID: 32087549 DOI: 10.1016/j.seizure.2020.02.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2019] [Revised: 01/05/2020] [Accepted: 02/06/2020] [Indexed: 11/29/2022] Open
Abstract
PURPOSE Epilepsy affects more than 50 million people worldwide and its management can be complicated by comorbidities such as impaired renal function. To optimize epilepsy control in patients with kidney disease, clinicians need to be aware of how antiepileptic drugs (AEDs) are affected by impaired renal function and how the kidneys are affected by epilepsy management strategies. Herein we present a narrative review with systematic literature search to discuss the use of AEDs in patients with renal impairment, including those undergoing dialysis, as well as the nephrotoxic effects of some AEDs. We finally conclude the article by providing practical tips about our approach to using AEDs in the setting of renal disease. METHODS A literature search targeting epilepsy management in patients with kidney disease was performed in MEDLINE database (1946 to 7th Jan 2019). RESULTS A total of 1193 articles were found. After duplicate removal, title and abstract screening followed by full text screening, a total of 110 references were included in this review. Additional information was included from drug product monographs. CONCLUSION The disposition of AEDs can be altered in patients with impaired renal function, leading to a higher risk of AED toxicity or therapy failure. Renal dosage adjustment and close monitoring is recommended. Although AED-induced nephrotoxicity is rare, it is unpredictable and clinicians need to vigilant about this possibility. In addition, AEDs renal adverse reactions and renal drug interactions should be considered when selecting an AED.
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Affiliation(s)
- Sherif Hanafy Mahmoud
- Clinical Associate Professor, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada.
| | - Xiao Ying Zhou
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada
| | - S Nizam Ahmed
- Professor of Medicine (Neurology) and Director, Clinical Neurophysiology Laboratory, Division of Neurology, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada
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9
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Orsucci D, Ienco EC, Siciliano G, Mancuso M. Mitochondrial disorders and drugs: what every physician should know. Drugs Context 2019; 8:212588. [PMID: 31391854 PMCID: PMC6668504 DOI: 10.7573/dic.212588] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Revised: 05/30/2019] [Accepted: 06/03/2019] [Indexed: 02/07/2023] Open
Abstract
Mitochondrial disorders are a group of metabolic conditions caused by impairment of the oxidative phosphorylation system. There is currently no clear evidence supporting any pharmacological interventions for most mitochondrial disorders, except for coenzyme Q10 deficiencies, Leber hereditary optic neuropathy, and mitochondrial neurogastrointestinal encephalomyopathy. Furthermore, some drugs may potentially have detrimental effects on mitochondrial dysfunction. Drugs known to be toxic for mitochondrial functions should be avoided whenever possible. Mitochondrial patients needing one of these treatments should be carefully monitored, clinically and by laboratory exams, including creatine kinase and lactate. In the era of molecular and ‘personalized’ medicine, many different physicians (not only neurologists) should be aware of the basic principles of mitochondrial medicine and its therapeutic implications. Multicenter collaboration is essential for the advancement of therapy for mitochondrial disorders. Whenever possible, randomized clinical trials are necessary to establish efficacy and safety of drugs. In this review we discuss in an accessible way the therapeutic approaches and perspectives in mitochondrial disorders. We will also provide an overview of the drugs that should be used with caution in these patients.
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Hamed SA, Rageh TA, Mohamad AO, Abou Elnour SM. Renal dysfunctions/injury in adult epilepsy patients treated with carbamazepine or valproate. Expert Rev Clin Pharmacol 2018; 11:819-824. [PMID: 30009654 DOI: 10.1080/17512433.2018.1501556] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
OBJECTIVES Clinical and subclinical laboratory evidence of renal proximal tubular dysfunction had been reported in children with epilepsy as an adverse effect of some antiepileptic drugs (AEDs). This study aimed to determine kidney function in adult patients with monosymptomatic epilepsy of unknown etiology and treated with valproate (VPA) or carbamazepine (CBZ). METHODS This study included 60 patients [mean age of 33.97 ± 6.70 years and treated with VPA (n = 24) or CBZ (n = 36) for mean duration of treatment of 6.03 ± 2.81years. Measurements of serum creatinine (sCr), urinary creatinine, creatinine clearance (CrCl) and serum kidney injury molecule 1 (KIM-1), markers of renal dysfunction/injury were done. RESULTS Compared to controls, patients had higher sCr, KIM-1 and lower CrCl levels. Compared to patients on VPA, those on CBZ had relatively higher KIM-1 and lower CrCl levels. We reported only significant correlations between KIM-1 with sCr (r = 0.324, p = 0.001) and duration of treatment with AEDs (r = 0.301, p = 0.02). CONCLUSION Chronic VPA and CBZ therapy may be associated with subclinical renal glomerular and/or proximal tubular dysfunctions or injuries. The treating neurologist have to consider this while selection of AED on start treating patients or modifying the AED for patients at high risk of kidney injury.
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Affiliation(s)
- Sherifa A Hamed
- a Department of Neurology and Psychiatry , Assiut University Hospital , Assiut , Egypt
| | - Tarek A Rageh
- a Department of Neurology and Psychiatry , Assiut University Hospital , Assiut , Egypt
| | - Amany O Mohamad
- b Department of Biochemistry , Assiut University Hospital , Assiut , Egypt
| | - Suzan M Abou Elnour
- a Department of Neurology and Psychiatry , Assiut University Hospital , Assiut , Egypt
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11
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Miño-Bernal JF, Alcaraz-Díaz LE, Zamora-Gómez S, Montenegro-Ibarra AC. Normal anion gap metabolic acidosis secondary to topiramate intake: case report. CASE REPORTS 2018. [DOI: 10.15446/cr.v4n2.69710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Introducción. El topiramato es un medicamento que se usa en el tratamiento de varios tipos de epilepsia y como profilaxis en casos de cefalea migrañosa. Entre sus mecanismos de acción, la inhibición de la anhidrasa carbónica en el riñón desencadena la excreción de orina alcalina ocasionando acidosis metabólica. Presentación del caso. Paciente femenino de 17 años procedente de la Ciudad de México con antecedente de consumo de topiramato, quetiapina y sertralina para manejo de síndrome depresivo, quien desarrolla acidosis metabólica de anión restante normal secundaria a ingesta de topiramato. La joven requiere soporte ventilatorio invasivo por deterioro del estado de conciencia y síndrome de dificultad respiratoria y presenta adecuada respuesta a manejo con catártico y bicarbonato sin compromiso renal y sin secuelas neurológicas. Discusión. La acidosis metabólica es la alteración ácido base más frecuente en la práctica clínica. La diferencia entre cationes y aniones medibles, conocida como anión restante o brecha aniónica, permite clasificar este tipo de acidosis. Las pérdidas de bicarbonato o trastornos de la función tubular renal generan acidosis de anión restante normal; por el contrario, la acidosis causada por sobreproducción de ácido endógeno o por insuficiencia renal genera anión restante elevado. El topiramato es una causa poco conocida de acidosis metabólica con anión restante normal; al inhibir la anhidrasa carbónica, se ocasiona una acidosis tubular renal mixta o tipo 3 debido a una incapacidad de secreción de hidrogeniones en el túbulo colector y una limitación en la reabsorción del bicarbonato en el túbulo proximal. Conclusión. El topiramato en dosis terapéutica o en sobredosis puede generar acidosis metabólica de anión restante normal debido a la inhibición de la anhidrasa carbónica a nivel renal. Se trata de un cuadro reversible en el cual el manejo con bicarbonato ha mostrado buenos resultados clínicos.
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12
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Barnett SM, Jackson AH, Rosen BA, Garb JL, Braden GL. Nephrolithiasis and Nephrocalcinosis From Topiramate Therapy in Children With Epilepsy. Kidney Int Rep 2018; 3:684-690. [PMID: 29854977 PMCID: PMC5976810 DOI: 10.1016/j.ekir.2018.02.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2017] [Revised: 01/26/2018] [Accepted: 02/13/2018] [Indexed: 11/30/2022] Open
Abstract
Introduction Adults treated with topiramate may develop nephrolithiasis, but its frequency in children on topiramate is unknown. Topiramate inhibits renal carbonic anhydrase, which can lead to renal tubular acidosis and hypercalciuria. We studied 40 consecutive children who initiated topiramate therapy for seizures between January 1997 and February 2003, followed for a mean of 36 months. Methods Serum electrolytes, urinary calcium/creatinine ratios, and renal ultrasonography were performed before topiramate and every 6 months thereafter. Results Four children developed nephrolithiasis and/or nephrocalcinosis, which resolved on discontinuation of topiramate. In 40 patients, the mean urinary calcium/creatinine ratio increased over time (P < 0.001). The mean serum bicarbonate in 40 patients decreased over time (P < 0.01). Twenty-three children had urinary calcium/creatinine ratios before topiramate. Nine children with baseline hypercalciuria (defined as urinary calcium/creatinine >0.21) were compared with the 14 children with baseline normal urinary calcium excretion. A greater increase in urinary calcium/creatinine ratios occurred in hypercalciuric children (P < 0.001) and a greater decrease in serum bicarbonate levels occurred in the hypercalciuric children (P < 0.05) compared with children with baseline normal calcium excretion. Greater urinary calcium excretion was associated with increasing doses of topiramate (P = 0.039). Conclusion Our study shows that long-term therapy with topiramate in children is associated with persistent hypercalciuria and metabolic acidosis, which can lead to nephrocalcinosis and/or nephrolithiasis. All children initiating topiramate therapy should have baseline and follow-up urinary calcium/creatinine studies, serum electrolytes, and periodic renal ultrasonography, if the urinary calcium/creatinine ratio increases to a level above normal for age.
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Affiliation(s)
- Sarah M Barnett
- Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts, USA.,Harvard Medical School, Boston, Massachusetts, USA.,Department of Pediatrics, Baystate Medical Center Children's Hospital, Springfield, Massachusetts, USA
| | - Anthony H Jackson
- Department of Pediatrics, Baystate Medical Center Children's Hospital, Springfield, Massachusetts, USA.,Baystate Medical Center Children's Hospital, Springfield, Massachusetts, USA.,University School of Medicine, Boston, Massachusetts, USA
| | - Beth A Rosen
- Department of Pediatrics, Baystate Medical Center Children's Hospital, Springfield, Massachusetts, USA.,Baystate Medical Center Children's Hospital, Springfield, Massachusetts, USA.,University School of Medicine, Boston, Massachusetts, USA
| | - Jane L Garb
- Baystate Medical Center Children's Hospital, Springfield, Massachusetts, USA.,University School of Medicine, Boston, Massachusetts, USA.,Department of Medicine, Baystate Medical Center, Springfield, Massachusetts, USA
| | - Gregory L Braden
- Baystate Medical Center Children's Hospital, Springfield, Massachusetts, USA.,University School of Medicine, Boston, Massachusetts, USA.,Department of Medicine, Baystate Medical Center, Springfield, Massachusetts, USA
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13
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Hamed SA. Topiramate induced peripheral neuropathy: A case report and review of literature. World J Clin Cases 2017; 5:446-452. [PMID: 29291205 PMCID: PMC5740191 DOI: 10.12998/wjcc.v5.i12.446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2017] [Revised: 08/11/2017] [Accepted: 09/03/2017] [Indexed: 02/05/2023] Open
Abstract
Drug-induced peripheral neuropathy had been rarely reported as an adverse effect of some antiepileptic drugs (AEDs) at high cumulative doses or even within the therapeutic drug doses or levels. We describe clinical and diagnostic features of a patient with peripheral neuropathy as an adverse effect of chronic topiramate (TPM) therapy. A 37-year-old woman was presented for the control of active epilepsy (2010). She was resistant to some AEDs as mono- or combined therapies (carbamazepine, sodium valproate, levetiracetam, oxcarbazepine and lamotrigine). She has the diagnosis of frontal lobe epilepsy with secondary generalization and has a brother, sister and son with active epilepsies. She became seizure free on TPM (2013-2017) but is complaining of persistent distal lower extremities paresthesia in a stocking distribution. Neurological examination revealed presence of diminished Achilles tendon reflexes, stocking hypesthesia and delayed distal latencies, reduced conduction velocities and amplitudes of action potentials of posterior tibial and sural nerves, indicating demyelinating and axonal peripheral neuropathy of the lower extremities. After exclusion of the possible causes of peripheral neuropathy, chronic TPM therapy is suggested as the most probable cause of patient's neuropathy. This is the first case report of topiramate induced peripheral neuropathy in the literature.
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Affiliation(s)
- Sherifa Ahmed Hamed
- Department of Neurology and Psychiatry, Assiut University Hospital, Assiut 71516, Egypt
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14
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Serrano-Castro PJ, Fernández-Pérez J, López-González FJ, Toledo-Argany M, Estévez-María JC, Arjona-Padillo A, Bertol-Alegre V, Mauri-Llerda JA, Tortosa-Conesa D, Ruiz-Giménez J, Querol-Pascual R, García-Martínez A, Molto-Jorda JM, Payán-Ortiz M, Maestre-Moreno JF, Galván-Espinosa J. Eslicarbazepine acetate and carotid intima-media thickness in epileptic patients. Epilepsy Res 2017; 138:81-87. [PMID: 29096133 DOI: 10.1016/j.eplepsyres.2017.10.018] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2017] [Revised: 10/11/2017] [Accepted: 10/24/2017] [Indexed: 02/08/2023]
Abstract
OBJECTIVE Evaluate if eslicarbazepine acetate (ESL) in combination with other non-inducer antiepileptic drugs (AEDs) in the treatment of epilepsy may represent a positive impact in the cardiovascular risk profile. METHODS multicentre, retrospective, observational, non-interventional, real-life study comparing patients treated with cytochrome P450 (CYP) inducer vs. ESL plus non-inducer AEDs. Primary endpoint: Carotid intima-media thickness (CIMT) measured following the Manheim Consensus criteria. RESULTS Patients included: 163. The main demographic, clinical and vascular risk parameters were comparable between the two groups except for duration of the disease, prevalence of dyslipidemia and use of lipid-lowering drugs (significantly higher in the inducers group) and number of previous antiepileptic drugs (significantly higher in the non-inducers group). Bivariate analysis of the main endpoint showed almost significant differences (p=0.05) in CIMT measures favourable to non-inducers (average 0.617mm+SD=0.148) vs. inducers (average 0.663mm+SD=0.147). Other variables reaching statistical significance were: age >50 years (p<0.001), high blood pressure (p<0.01) and dyslipidemia (p<0.05). A multivariate analysis including these variables and biochemical vascular risk factors showed a predictor model including two variables: inducers group (p=0.031; Coefficient β=0.234) and age >50 years (p=0.001; Coefficient β=0.387). Regarding gender, the mean CIMT in males was significantly higher in the inducers (0.693mm; SD=0.139) than in the non- inducers groups (0.628mm; SD=0.151; p<0.05). In females the differences were not significant. SIGNIFICANCE The use of CYP inducer AEDs is associated with a significant increase in CIMT as compared with ESL and other non-inducer AEDs. The study shows a decrease in the vascular risk measured by ultrasound criteria in male patients treated with ESL compared with patients treated with inducer AEDs.
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Affiliation(s)
- Pedro Jesús Serrano-Castro
- Hospital Regional Universitario de Málaga, Neurology, Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain..
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - José Galván-Espinosa
- Complejo Hospitalario Torrecárdenas, Fundación Investigación Biosanitaria Andalucía Oriental (FIBAO), Almería, Spain
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15
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Parikh S, Goldstein A, Karaa A, Koenig MK, Anselm I, Brunel-Guitton C, Christodoulou J, Cohen BH, Dimmock D, Enns GM, Falk MJ, Feigenbaum A, Frye RE, Ganesh J, Griesemer D, Haas R, Horvath R, Korson M, Kruer MC, Mancuso M, McCormack S, Raboisson MJ, Reimschisel T, Salvarinova R, Saneto RP, Scaglia F, Shoffner J, Stacpoole PW, Sue CM, Tarnopolsky M, Van Karnebeek C, Wolfe LA, Cunningham ZZ, Rahman S, Chinnery PF. Patient care standards for primary mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society. Genet Med 2017; 19:S1098-3600(21)04766-3. [PMID: 28749475 PMCID: PMC7804217 DOI: 10.1038/gim.2017.107] [Citation(s) in RCA: 168] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2017] [Accepted: 05/25/2017] [Indexed: 02/07/2023] Open
Abstract
The purpose of this statement is to provide consensus-based recommendations for optimal management and care for patients with primary mitochondrial disease. This statement is intended for physicians who are engaged in the diagnosis and management of these patients. Working group members were appointed by the Mitochondrial Medicine Society. The panel included members with several different areas of expertise. The panel members utilized surveys and the Delphi method to reach consensus. We anticipate that this statement will need to be updated as the field continues to evolve. Consensus-based recommendations are provided for the routine care and management of patients with primary genetic mitochondrial disease.
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Affiliation(s)
- Sumit Parikh
- Center for Child Neurology, Cleveland Clinic Children’s Hospital, Cleveland, Ohio, USA
| | - Amy Goldstein
- Division of Child Neurology, Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Amel Karaa
- Division of Genetics, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Mary Kay Koenig
- Division of Child and Adolescent Neurology, University of Texas Medical School at Houston, Houston, Texas, USA
| | - Irina Anselm
- Department of Neurology, Boston Children’s Hospital, Boston, Massachusetts, USA
| | | | - John Christodoulou
- Neurodevelopmental Genomics Research Group, Murdoch Childrens Research Institute, and Department of Paediatrics, Melbourne Medical School, University of Melbourne, Melbourne, Australia
| | - Bruce H. Cohen
- Neurodevelopmental Science Center, Children’s Hospital Medical Center of Akron, Akron, Ohio, USA
| | - David Dimmock
- Rady Children’s Institute for Genomic Medicine, San Diego, California, USA
| | - Gregory M. Enns
- Division of Medical Genetics, Department of Pediatrics, Stanford University Lucile Packard Children’s Hospital, Palo Alto, California, USA
| | - Marni J. Falk
- Division of Human Genetics, Department of Pediatrics, The Children’s Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Annette Feigenbaum
- Division of Clinical and Metabolic Genetics, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada
- Department of Pediatrics, University of California San Diego and Rady Childrens Hospital, San Diego, California, USA
| | - Richard E. Frye
- Department of Pediatrics, University of Arkansas Medical Sciences, Little Rock, Arkansas, USA
| | - Jaya Ganesh
- Division of Genetics, Department of Pediatrics, Cooper Medical School at Rowan University, Camden, New Jersey, USA
| | - David Griesemer
- Division of Neurology, Levine Children’s Hospital, Charlotte, North Carolina, USA
| | - Richard Haas
- Departments of Neurosciences and Pediatrics, University of California San Diego, La Jolla, California, USA
- Department of Neurosciences, Rady Children’s Hospital, San Diego, California, USA
| | - Rita Horvath
- Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK
| | - Mark Korson
- Genetic Metabolic Center for Education, Salem, Massachusetts, USA
| | - Michael C. Kruer
- Department of Pediatric Neurology, University of Arizona College of Medicine, Phoenix, Arizona, USA
| | - Michelangelo Mancuso
- Department of Experimental and Clinical Medicine, Neurological Clinic, University of Pisa, Pisa, Italy
| | - Shana McCormack
- Division of Endocrinology and Diabetes, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
| | | | - Tyler Reimschisel
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Ramona Salvarinova
- Division of Biochemical Diseases, BC Children’s Hospital, British Columbia, Canada
| | - Russell P. Saneto
- Department of Neurology, Seattle Children’s Hospital/University of Washington, Seattle, Washington, USA
| | - Fernando Scaglia
- Department of Molecular and Human Genetics, Baylor College of Medicine and Texas Children’s Hospital, Houston, Texas, USA
| | - John Shoffner
- Neurology, Biochemical & Molecular Genetics, Atlanta, Georgia, USA
| | - Peter W. Stacpoole
- Department of Medicine, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Carolyn M. Sue
- Department of Neurology and Kolling Institute, Royal North Shore Hospital, St Leonards, Australia
| | - Mark Tarnopolsky
- Division of Neurology, McMaster University, Hamilton, Ontario, Canada
| | - Clara Van Karnebeek
- Department of Pediatrics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
- Department of Pediatrics, Centre for Molecular Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Lynne A. Wolfe
- Undiagnosed Diseases Network, National Institutes of Health, Bethesda, Maryland, USA
| | | | - Shamima Rahman
- Mitochondrial Research Group, UCL Great Ormond Street Institute of Child Health, London, UK
| | - Patrick F. Chinnery
- Department of Clinical Neurosciences & MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK
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Messinger MM, Misra SN, Clark GD, DiCarlo SM. Evaluation of Safety in Exceeding Maximum Adult Doses of Commonly Used Second-Generation Antiepileptic Drugs in Pediatric Patients. J Pediatr Pharmacol Ther 2017; 22:256-260. [PMID: 28943819 DOI: 10.5863/1551-6776-22.4.256] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
OBJECTIVE Pediatric patients often require larger doses of antiepileptic drug (AED) than adults in order to attain therapeutic serum concentrations and/or achieve seizure control. Safety and efficacy data are often extrapolated from adult literature; hence, optimal dosage may only be determined anecdotally or based on expert opinion. With limited pediatric dosing guidelines, milligrams per day that are based on weight may exceed the maximum adult dose. The primary objective of this study is to evaluate the safety of exceeding maximum doses as specified by the US Food and Drug Administration or manufacturers of commonly used AEDs in pediatric patients. METHODS This study is a single-center, retrospective analysis of all pediatric patients seen in the outpatient clinic between October 2010 and October 2014 who were prescribed a dose that exceeds the maximum approved dose of oxcarbazepine, zonisamide, topiramate, levetiracetam, lamotrigine, or clobazam. Baseline demographics (ie, sex, age, race/ethnicity, weight, height, diagnosis), serum drug concentrations, and appropriate laboratory tests were collected. Side effects were reviewed. RESULTS During the 4-year study period, 41,137 prescriptions were included. A total of 2% of prescriptions exceeded the maximum dose of 1 of the included AEDs. The most common AED prescribed above the maximum dose was levetiracetam (53%), whereas lamotrigine was the least common (6%). The largest doses prescribed exceeded the maximum by 3-fold (i.e., levetiracetam dose of 9000 mg/day). CONCLUSION It appears safe to use doses exceeding the maximum approved dose of the evaluated AEDs in pediatric patients, with appropriate counseling and monitoring for adverse effects.
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Hamed SA. The effect of antiepileptic drugs on the kidney function and structure. Expert Rev Clin Pharmacol 2017; 10:993-1006. [PMID: 28689437 DOI: 10.1080/17512433.2017.1353418] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2017] [Accepted: 07/06/2017] [Indexed: 11/08/2022]
Abstract
Long-term use of antiepileptic drugs (AEDs) is associated with number of somatic conditions. Data from experimental, cross-sectional and prospective studies have evidence for the deleterious effect of some AEDs on the kidney. Areas covered: This review summarized the current knowledge of the effect of AEDs on the kidney including evidence and mechanisms. Fanconi syndrome was reported with valproate (VPA) therapy in severely disabled children with epilepsy. Renal tubular acidosis and urolithiasis were reported with acetazolamide, topirmate and zonisamide, drugs with carbonic anhydrase inhibition properties. Increased levels of urinary N-acetyl-beta-D-glucosaminidase (NAG) to urinary creatinine (U-NAG/UCr), urinary excretion of α1-micrglobulin, β-galactosidase activity; and urinary malondialdehyde to creatinine (MDA/Cr), markers of renal glomerular and tubular injury, were reported with chronic use of some AEDs (VPA, carbamazepine and phenytoin). The mechanism(s) of kidney dysfunction/injury induced by AEDs is unknown. Experimental and clinical studies have shown that VPA induces oxidative stress, mitochondrial deficits, carnitine deficiency and inflammation and fibrosis in renal tissue in mice and in vitro studies. Expert commentary: It seems reasonable to monitor kidney function during treating patients with epilepsy at high risk of kidney injury (e.g. on combined therapy with more than one AED, severely disabled children, etc).
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Affiliation(s)
- Sherifa Ahmed Hamed
- a Department of Neurology and Psychiatry , Assiut University Hospital , Assiut , Egypt
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18
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Chromatographic determination of zonisamide, topiramate and sulpiride in plasma by a fluorescent 'turn-on' chemosensor. Bioanalysis 2017; 9:1049-1064. [PMID: 28737428 DOI: 10.4155/bio-2017-0090] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
AIM Antiepileptics (AEDs) and antipsychotics are often coprescribed. Interactions between these drugs may affect both efficacy and toxicity. Therefore, drug monitoring is necessary for appropriate dosage adjustments. MATERIALS & METHODS Specific 'turn-on' chemosensor, 4-chloro-7-nitrobenzofurazan is used for selective and sensitive determination of two AEDs: zonisamide (ZON) and topiramate (TOP) with the antipsychotic sulpiride (SUL) in epileptic patients' plasma followed by reversed-phase-HPLC separation without any interference. RESULTS Linear behavior was observed in the range of 0.1-3 μg/ml and 0.01-0.5 μg/ml for the AEDs and SUL, respectively, with LOD of 33, 46 and 4 ng/ml and LOQ of 86, 93 and 9 ng/ml for ZON, TOP and SUL, respectively. The proposed method was successfully applied for determination of different pharmacokinetic parameters of ZON and TOP, and for clinical monitoring of the three drugs in healthy volunteers following oral administration. CONCLUSION The developed method is suitable for the routine therapeutic drug monitoring of these drugs.
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20
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Gok M, Ozdemir O. Effect of topiramate on choroidal thickness and anterior chamber parameters in the treatment of patients with migraine. Cutan Ocul Toxicol 2017; 36:381-386. [PMID: 28351170 DOI: 10.1080/15569527.2017.1311337] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
OBJECTIVE To investigate the effects of topiramate on choroidal thickness and anterior chamber parameters using optical coherence tomography in the treatment of patients with migraine. METHODS A total of 22 eyes of 22 adults (12 females, 10 males) diagnosed with migraine and scheduled to topiramate treatment for pain control were recruited in this prospective study. Choroidal thickness (CT), anterior chamber depth (ACD), anterior chamber angle (ACA), spherical refractive equivalent (SphEq) and intraocular pressure (IOP) measurements were recorded at baseline (prior the topiramate therapy), first and second month visits for the statistical analysis. One-way ANOVA with repeated measures test was used for the statistical evaluation. RESULTS Mean age of the patients was 40.2 ± 6.5 years. Mean CT at central fovea was 324 ± 47 μm initially, 341 ± 45 μm in the first month and 344 ± 46 μm in the second month, thus first and second month measures were significantly higher than base values (p < 0.001). There was also a slight increase in IOP values among baseline (15.5 ± 2.4 mmHg) and follow-up visits (17.5 ± 2.6 mmHg, 19.0 ± 3.3 mmHg, respectively, ` p = 0.001). Baseline ACD (3.66 ± 0.22 mm) measures significantly decreased at the first month (3.63 ± 0.22 mm) and second month (3.62 ± 0.22 mm, p = 0.009). Also, a significant reduction was detected in the first (36.2 ± 4.9°) and second month (35.9 ± 5.1°) ACA measures comparing with baseline (39.1 ± 5.1°, p = 0.05). A significant myopic shift was determined in the first and second month SphEq values (-0.08 ± 0.6, -0.10 ± 0.6, respectively, p = 0.05). CONCLUSIONS The study revealed increased CT and altered anterior chamber parameters and IOP due to topiramate therapy. Therefore, the patients using topiramate should be carefully monitored by an ophthalmologist considering the possible side effects.
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Affiliation(s)
- Mustafa Gok
- a Department of Ophthalmology , Ordu University Faculty of Medicine , Ordu , Turkey and
| | - Ozdemir Ozdemir
- b Department of Ophthalmology , Zekai Tahir Burak Women's Health Education and Research Hospital , Ankara , Turkey
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Hilgers A, Schaefer M. Systematic Adverse Drug Reaction Monitoring of Patients Under Newer Antiepileptic Drugs Using Routine Clinical Data of Inpatients. Drugs Real World Outcomes 2016; 3:209-221. [PMID: 27398300 PMCID: PMC4914536 DOI: 10.1007/s40801-016-0077-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
Abstract
BACKGROUND Based on data of clinical trials, new agents are receiving approval to the pharmaceutical market, for which information concerning safety issues under real-life conditions is not yet available. OBJECTIVES The aim was to evaluate the tolerability of newer antiepileptic drugs (AEDs), such as topiramate, levetiracetam, zonisamide, pregabalin, extended-release oxcarbazepine, lacosamide and eslicarbazepine, under real-life conditions by means of an assessment of routine clinical data of inpatients. METHOD Over 2.75 years data of all inpatients receiving one of the newer AEDs were documented. Occurring adverse drug reactions (ADRs) were classified according to the WHO-UMC Causality Assessment concerning their likely relationship to the prescribed AEDs. For each AED, the total number of patients without and with ADRs, assessed as at least possibly related to the particular drug, was calculated and corresponding incidences compared with reference data provided in the Summary of Product Characteristics (SmPC). For statistical evaluation Spearman correlation (rs), estimated relative risk and logistic regression analysis were used. RESULTS In total, the data of 562 patients were assessed, of which 90 % received up to six different AEDs. The proportion of off-label use with regard to dosage varied between 6.4 and 64.7 %. Levetiracetam and oxcarbazepine as an extended-release formulation were most commonly used, and levetiracetam showed the best tolerance. By using logistic regression, the occurrence of ADRs was significantly associated with the number of AEDs (p < 0.001) as well as the defined daily doses (p = 0.003). In total, ADRs of AEDs were documented for 318 patients (56.6 %). The most common referred to electrolyte imbalance, e.g., low sodium (n = 79, 14.1 %) and potassium (n = 25, 4.4 %) levels, the central nervous system, including dizziness (n = 61, 10.9 %), disturbed vision (n = 47, 8.4 %), fatigue (n = 40, 7.1 %), nystagmus (n = 36, 6.4 %) and ataxia (n = 29, 5.2 %), or cognitive deficits, especially disturbance of speech (n = 37, 6.6 %), memory impairment (n = 36, 6.4 %) and mental slowing (n = 32, 5.7 %). By comparing the assessed ADR incidences with specification data, for some ADRs, a probable underestimation by the SmPC of respective risk could be assumed. CONCLUSION During inpatient treatment, valuable data are generated, which are currently rarely utilized for pharmacoepidemiologic or pharmacovigilance purposes. A systematic evaluation of these data can increase the probability of detecting ADRs and can promote real-life-related drug surveillance.
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Affiliation(s)
- Annika Hilgers
- Ev. Krankenhaus Bielefeld gGmbH, Bethesdaweg 10, 33617 Bielefeld, Germany
- Epilepsiezentrum Bethel, Krankenhaus Mara gGmbH, 33617 Bielefeld, Germany
- Charité Universitätsmedizin Berlin, Institut für klinische Pharmakologie, 10115 Berlin, Germany
| | - Marion Schaefer
- Charité Universitätsmedizin Berlin, Institut für klinische Pharmakologie, 10115 Berlin, Germany
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Hesami O, Hosseini SS, Kazemi N, Hosseini-Zijoud SM, Moghaddam NB, Assarzadegan F, Mokhtari S, Fakhraee S. Evaluation of Ocular Side Effects in the Patients on Topiramate Therapy for Control of Migrainous Headache. J Clin Diagn Res 2016; 10:NC01-4. [PMID: 27134906 DOI: 10.7860/jcdr/2016/16263.7339] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2015] [Accepted: 11/19/2015] [Indexed: 11/24/2022]
Abstract
INTRODUCTION Topiramate, a sulfa-derivative monosaccharide, is an antiepileptic drug which is administered in the control of migraine. It is reported to cause various ocular side effects such as visual field defect and myopic shift. To investigate the alterations in refractive error, properties of the cornea and changes in the anterior chamber in patients that receive Topiramate for migraine control. MATERIALS AND METHODS This is a hospital-based, non-interventional, observational study that is conducted at Imam Hossein Hospital, affiliated to Shahid Beheshti University of Medical Sciences, Department of Neurology, in collaboration with the department of Ophthalmology. Thirty three consecutive patients with the diagnosis of migraine that were candidate for Topiramate therapy were recruited. Patients with history of ocular trauma or surgery, keratoconus, glaucoma, congenital ocular malformations and any history of unexplained visual loss were excluded. After thorough ophthalmic examination, all the patients underwent central corneal thickness (CCT) measurement, and Pentacam imaging (Scheimpflug camera) at the baseline. Various parameters were extracted and used for analysis. Anterior chamber volume (ACV), anterior chamber depth (ACD), and anterior chamber angle (ACA) measurement was performed. These measurements were repeated on day 30(th) and 90(th) after the initiation of Topiramate therapy. According to the normality tests, parameters with normal distribution were analysed using the repeated measures test and the remaining parameters (with non-normal distribution) were analysed using the non-parametric k-sample test. A p-value< 0.05 was considered statistically significant, according to Bonferroni post hoc correction. RESULTS There were 66 eyes of 33 patients under the diagnosis of migrainous headache, that Topiramate was initiated for headache control, included in the study. The mean value of refractive error had a statistically significant myopic change, from -0.23 diopters (D) at the baseline to -0.61 D at the 90(th) day of follow-up period (p-value < 0.001). Mean CCT was 531.43 μm at the baseline and increased to 534.72 μm at the 30(th) day, and 537.51 μm at the 90(th) day after the administration of Topiramate (p-value=0.001). Mean value of other parameters, ACV, ACD, and ACA, did not reveal statistically significant change. CONCLUSION Myopic shift and gradually increasing CCT in the patients after Topiramate administration should be considered before any refractive surgery. We found no gradual change in the anterior chamber and angle parameters in our patients in the 90 days of follow up. More studies with a longer duration of follow-up are needed to elucidate dose-dependent ocular manifestations.
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Affiliation(s)
- Omid Hesami
- Assistant Professor, Department of Neurology, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences (SBMU) , Tehran, Iran
| | | | - Nasim Kazemi
- Neurologist, Dezful University of Medical Sciences , Dezful, Iran
| | - Seyed-Mostafa Hosseini-Zijoud
- Social Development and Health Promotion Research Center, Kermanshah University of Medical Sciences , Kermanshah, Iran
| | - Nahid Beladi Moghaddam
- Assistant Professor, Department of Neurology, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences (SBMU) , Tehran, Iran
| | - Farhad Assarzadegan
- Assistant Professor, Department of Neurology, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences (SBMU) , Tehran, Iran
| | - Sara Mokhtari
- Optometrist, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences (SBMU) , Tehran, Iran
| | - Shahrzad Fakhraee
- Assistant of Neurology, Department of Neurology, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences (SBMU) , Tehran, Iran
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A candidate-gene association study of topiramate-induced weight loss in obese patients with and without type 2 diabetes mellitus. Pharmacogenet Genomics 2016; 26:53-65. [DOI: 10.1097/fpc.0000000000000185] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Dell'Orto VG, Belotti EA, Goeggel-Simonetti B, Simonetti GD, Ramelli GP, Bianchetti MG, Lava SAG. Metabolic disturbances and renal stone promotion on treatment with topiramate: a systematic review. Br J Clin Pharmacol 2015; 77:958-64. [PMID: 24219102 DOI: 10.1111/bcp.12283] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2013] [Accepted: 10/31/2013] [Indexed: 11/29/2022] Open
Abstract
AIMS The use of topiramate, which is prescribed for the management of epilepsy, for migraine headache prophylaxis and as a weight-loss agent, has been associated with the development of metabolic acidosis, hypokalaemia and renal stone disease. We systematically reviewed all the literature. METHODS The systematic review of the literature was realized using the principles underlying the UK Economic and Social Research Council guidance on the conduct of narrative synthesis and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. RESULTS Fourty-seven reports published between 1996 and 2013 were retained for the final analysis. Five case-control studies and six longitudinal studies addressed the effect of topiramate on acid-base and potassium balance. A significant tendency towards mild-to-moderate hyperchloraemic metabolic acidosis (with bicarbonate ≤21.0 mmol l(-1) in approximately every third case) and mild hypokalaemia (with potassium ≤3.5 mmol l(-1) in 10% of the cases) was noted on treatment with topiramate, which was similar in children and adults. A single study observed that topiramate causes mild hyperuricaemia in male adults. A tendency towards hypocitraturia, a recognized promoter of renal stone formation, was noted in all patients on topiramate. CONCLUSIONS Increasing evidence supports the use of topiramate. Topiramate is generally well tolerated, and serious adverse events are rare. Nonetheless, the present systematic review of the literature indicates that its use is linked with the development of acidosis, hypokalaemia, hyperuricaemia and hypocitraturia.
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Affiliation(s)
- Valentina G Dell'Orto
- Department of Pediatrics, San Giovanni Hospital, Bellinzona, Switzerland; University of Berne, Berne, Switzerland
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Abstract
The anticonvulsant topiramate not only decreases ethanol consumption in alcohol dependence (AD) but also may produce several adverse events including cognitive impairment. Zonisamide is a structurally related anticonvulsant that is a promising agent for the treatment of AD and may have greater tolerability than topiramate. This study evaluated the effects of zonisamide (400 mg/d) on alcohol consumption and its neurotoxic effects in subjects with AD. A double-blind placebo-controlled clinical trial was conducted using 2 comparator anticonvulsant drugs, topiramate (300 mg/d) and levetiracetam (2000 mg/d), which does not impair cognition. Study medications were administered for 14 weeks, including a 2-week taper period. Medication adherence was facilitated using Brief Behavioral Compliance Enhancement Treatment. The neurotoxicity of the study drugs was assessed using neuropsychological tests and the AB-Neurotoxicity Scale. Compared with placebo, both zonisamide and topiramate produced significant reductions in the drinks consumed per day, percent days drinking, and percent days heavy drinking. Only the percent days heavy drinking was significantly decreased in the levetiracetam group. The topiramate cell was the only group that had a significant increase on the mental slowing subscale of the Neurotoxicity Scale compared with placebo at study weeks 11 and 12. Topiramate and zonisamide both produced modest reductions in verbal fluency and working memory. These findings indicate that zonisamide may have efficacy in the treatment of AD, with effect sizes similar to topiramate. Both of these drugs produced similar patterns of cognitive impairment, although only the topiramate group reported significant increases in mental slowing.
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Abstract
Topiramate belongs to the new class of neuromodulators, which has carbonic anhydrase inhibitor activity and been associated with renal calculi. It has also been shown to cause renal potassium wasting; however, it is generally clinically insignificant. Here, we describe a case of refractory hypokalemia in a patient with severe comorbidities who was on topiramate for seizures.
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Cure E, Kirbas A, Tumkaya L, Cure MC, Sahin OZ, Kalkan Y, Yuce S, Altuner D. Effect of infliximab against cisplatin-induced nephrotoxicity. Saudi Med J 2014; 35:953-958. [PMID: 25228176 PMCID: PMC4362156 DOI: pmid/25228176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2014] [Accepted: 07/16/2014] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVES To investigate whether infliximab (Ib), an inhibitor of tumor necrosis factor alpha (TNF-α), prevents cisplatin (Cis)-induced nephrotoxicity. METHODS The study was performed in the Department of Internal Medicine, Recep Tayyip Erdogan University, Rize, Turkey, between November 2012 and May 2013. Thirty male Wistar albino rats were divided into 3 groups, a control group, a Cis group, and a Cis+Ib group. The animals of the Cis group were injected with a single dose (7 mg/kg) of Cis intraperitoneally. The animals of the Cis+Ib group were injected with a single dose (7 mg/kg) of Ib 72 hours prior to Cis injection. RESULTS The TNF-α, interleukin-1 beta (IL-1b), nitric oxide (NO) and adenosine deaminase (ADA) levels of the Cis group were higher than both the control group TNF-α (p<0.001), IL-1α (p<0.001), NO (p<0.001) and ADA (p<0.001), and the Cis+Ib group TNF-α (p<0.001), IL-1b (p<0.001), NO (p<0.001), and ADA (p=0.003). Histopathological examination revealed extensive damage in the Cis group, while the damage in the Cis+Ib group was lower. While the carbonic anhydrase II (CA-II) level of the Cis group was lower than both groups, it was similar in the Cis+Ib and the control groups. CONCLUSION Infliximab acts against Cis-induced nephrotoxicity by a strong inhibition of TNF-α. Additionally, the combination of these 2 drugs does not obviously change the level of CA-II.
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Affiliation(s)
- Erkan Cure
- Department of Internal Medicine, School of Medicine, Recep Tayyip Erdogan University, Rize 53100, Turkey. Tel. +90 (464) 2130491 Ext. 1859. Fax. +90 (464) 2170364. E-mail.
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Cohen LP, Wong J, Jiwani AZ, Greenstein SH, Brauner SC, Chen SC, Turalba AV, Chen TC, Shen L, Rhee DJ, Wiggs JL, Kang JH, Loomis S, Pasquale LR. A survey of preoperative blood tests in primary open-angle glaucoma patients versus cataract surgery patients. Digit J Ophthalmol 2014; 20:20-8. [PMID: 25097461 DOI: 10.5693/djo.01.2014.02.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
PURPOSE To investigate biomarker differences in routine preoperative blood tests performed on primary open-angle glaucoma (POAG) case and control patients presenting for anterior segment eye surgery. METHODS POAG cases and age-related cataract surgery patients (controls) who underwent anterior segment surgery at Massachusetts Eye and Ear from January 2009 through March 2012 were identified by retrospective record review. Patients with diabetes mellitus, secondary glaucoma, and cataract due to trauma or steroid exposure were excluded. Data on demographic features, preoperative ophthalmological and medical diagnosis, blood pressure, anthropometric measures, basic metabolic panel, and complete blood count were extracted from the medical records. Univariate differences in lab values between POAG cases and controls were assessed using unpaired t tests. Multivariate logistic regression analysis was completed to determine the independent associations of biomarkers with POAG. RESULTS A total of 150 cases and 150 age-related controls were included. In multivariate analysis, higher AG was inversely associated with POAG (odds ratio [OR] = 0.90; 95% confidence interval [CI], 0.80-1.00), and higher Cl- level was positively associated with POAG (OR = 1.15; 95% CI, 1.02-1.29). The lower AG in POAG patients could be explained by higher IgG levels as the available data in post hoc analysis showed a nonsignificant trend toward higher IgG in cases compared to controls (17 vs 23; 1142 ± 284 mg/dl vs 1028 ± 291 mg/dl; P = 0.22). Furthermore, in multivariable analysis, a higher red blood cell count was also associated with POAG (OR = 1.91; 95% CI, 1.11-3.28). CONCLUSIONS Patients with POAG presenting for anterior segment surgery had a lower AG compared to age-related cataract surgery patients. The etiology of this reduced gap is unclear but the possible contribution of IgG warrants further exploration. The etiology of higher red blood cell counts in POAG cases is unknown and deserves further exploration.
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Affiliation(s)
- Laura P Cohen
- Glaucoma Service, Massachusetts Eye and Ear and Harvard Medical School, Boston, Massachusetts
| | - Jessica Wong
- Glaucoma Service, Massachusetts Eye and Ear and Harvard Medical School, Boston, Massachusetts
| | - Aliya Z Jiwani
- Glaucoma Service, Massachusetts Eye and Ear and Harvard Medical School, Boston, Massachusetts
| | - Scott H Greenstein
- Comprehensive Ophthalmology Service, Massachusetts Eye and Ear and Harvard Medical School, Boston, Massachusetts
| | - Stacey C Brauner
- Glaucoma Service, Massachusetts Eye and Ear and Harvard Medical School, Boston, Massachusetts; ; Comprehensive Ophthalmology Service, Massachusetts Eye and Ear and Harvard Medical School, Boston, Massachusetts
| | - Sherleen C Chen
- Comprehensive Ophthalmology Service, Massachusetts Eye and Ear and Harvard Medical School, Boston, Massachusetts
| | - Angela V Turalba
- Glaucoma Service, Massachusetts Eye and Ear and Harvard Medical School, Boston, Massachusetts
| | - Teresa C Chen
- Glaucoma Service, Massachusetts Eye and Ear and Harvard Medical School, Boston, Massachusetts
| | - Lucy Shen
- Glaucoma Service, Massachusetts Eye and Ear and Harvard Medical School, Boston, Massachusetts
| | - Douglas J Rhee
- Glaucoma Service, Massachusetts Eye and Ear and Harvard Medical School, Boston, Massachusetts
| | - Janey L Wiggs
- Glaucoma Service, Massachusetts Eye and Ear and Harvard Medical School, Boston, Massachusetts
| | - Jae Hee Kang
- Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts
| | - Stephanie Loomis
- Glaucoma Service, Massachusetts Eye and Ear and Harvard Medical School, Boston, Massachusetts
| | - Louis R Pasquale
- Glaucoma Service, Massachusetts Eye and Ear and Harvard Medical School, Boston, Massachusetts; ; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts
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Abstract
INTRODUCTION Migraine is a very common medical disorder characterized by attacks of moderate-severe headache, nausea and disability. Topiramate is an effective, popular prophylactic migraine treatment, which is approved for use in adults and adolescents. Due to its multiple mechanisms of action, topiramate has multiple potential safety issues, including systemic and CNS adverse events, which may complicate therapy. AREAS COVERED This review evaluates common adverse events as seen in the pivotal trials of topiramate for migraine as well as those observed in postmarketing studies. These include weight loss, metabolic acidosis, renal calculi, acute angle closure glaucoma, visual distortions and cognitive slowing. Topiramate use during pregnancy is associated with an increased risk of cleft lip. This review highlights both common and unusual safety issues associated with topiramate use, including important drug interactions and a comparison with other migraine prophylactic agents. EXPERT OPINION Topiramate is highly effective in migraine prophylaxis but clinicians using the drug need to be aware of the potential for bothersome or serious adverse events. When treating with topiramate, use a slow titration to the goal dose of 100 mg or the lowest dose, which helps prevent migraine.
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Affiliation(s)
- Michael J Marmura
- Thomas Jefferson University, Jefferson Headache Center, Department of Neurology , 900 Walnut Street, Suite 200, PA 19107 , USA +1 215 955 2243 ; +1 215 955 2060 ;
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Jovanović M, Sokić D, Grabnar I, Prostran M, Obrenović R, Vučićević K, Miljković B. Effect of Long-term Topiramate Therapy on Serum Bicarbonate and Potassium Levels in Adult Epileptic Patients. Ann Pharmacother 2014; 48:992-997. [PMID: 24811395 DOI: 10.1177/1060028014534397] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Topiramate (TPM) is a sulfamate-substituted monosaccharide that is structurally different from other antiepileptic drugs. TPM inhibits carbonic anhydrase activity, which is associated with loss of bicarbonate from the kidney and consequently metabolic acidosis or electrolyte imbalance. OBJECTIVE The objectives of the study were to investigate the influence of TPM therapy on bicarbonate and potassium levels in adult epileptic patients. METHODS Data were collected from 59 adult patients on monotherapy or co-therapy of TPM and other antiepileptic drugs. Serum bicarbonate and potassium levels were available from all patients. Steady-state TPM trough concentrations were determined in blood samples by high-performance liquid chromatography. Data analysis was performed by SPSS software (version 17, Chicago, IL). RESULTS Patients were divided into group A (duration of therapy shorter than or equal to 5 years) and group B (duration of therapy longer than 5 years). Significant difference (P < 0.05) in serum bicarbonate levels was observed between these 2 groups. Bicarbonate levels were linearly related to the TPM therapy duration. No correlation was found between the TPM dose or patient age and bicarbonate or potassium levels, as well as between therapy duration and potassium level. Linear regression analysis showed no significant association among 54 available TPM trough concentrations and bicarbonate or potassium levels. CONCLUSIONS Results highlight the frequent occurrence of lower bicarbonate level associated with prolonged TPM therapy. Monitoring bicarbonate levels in patients on long-term TPM therapy might be useful.
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Affiliation(s)
- Marija Jovanović
- Department of Pharmacokinetics and Clinical Pharmacy, University of Belgrade - Faculty of Pharmacy, Belgrade, Serbia
| | - Dragoslav Sokić
- Clinic of Neurology, Clinical Centre of Serbia, Belgrade, Serbia University of Belgrade - Faculty of Medicine, Belgrade, Serbia
| | - Iztok Grabnar
- Department of Biopharmaceutics and Pharmacokinetics, University of Ljubljana - Faculty of Pharmacy, Ljubljana, Slovenia
| | - Milica Prostran
- Department of Pharmacology, Clinical Pharmacology and Toxicology, University of Belgrade - Faculty of Medicine, Belgrade, Serbia
| | - Radmila Obrenović
- Centre of Medical Biochemistry, Clinical Centre of Serbia, Belgrade, Serbia
| | - Katarina Vučićević
- Department of Pharmacokinetics and Clinical Pharmacy, University of Belgrade - Faculty of Pharmacy, Belgrade, Serbia
| | - Branislava Miljković
- Department of Pharmacokinetics and Clinical Pharmacy, University of Belgrade - Faculty of Pharmacy, Belgrade, Serbia
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Abstract
INTRODUCTION Carbonic anhydrase (CA) inhibitors have an impressive safety record despite the multiple functions that CA isozymes serve because they are not fully inhibited with most dosing. While reducing the targeted CA-dependent process sufficiently for disease control, residual activity and uncatalyzed rates in combination with compensations are adequate to avoid lethal consequences. Some drugs have in vitro selectivity differences against the 13 active isozymes, but none are convincingly selective in vivo or clinically. Efforts to synthesize selective inhibitors should result in safer drugs with fewer side effects. AREAS COVERED This review will focus on approved drugs with CA-inhibiting activity, whether used directly for this purpose or others. Side effects are discussed in relation to various organ systems and the disease being treated. Causes of side effects are considered, and strategies for symptom reduction are given. EXPERT OPINION Common side effects of paresthesias, dyspepsia, lassitude and fatigue in 30 - 40% of patients are generally tolerable or abate, but if not can be partially relieved by bicarbonate supplementation. The most important safety concerns are severe acidosis, respiratory failure and encephalopathy in patients with renal, pulmonary and hepatic disease where caution is critical, as is also the case in persons with sulfa drug allergies.
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Affiliation(s)
- Erik R Swenson
- University of Washington - Medical Service, VA Puget Sound Health Care System , 1660 S Columbian Way, S-111-PLUM, Seattle, WA 98108 , USA
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Abstract
Carbonic anhydrases are ubiquitous enzymes that catalyze the reversible hydration of carbon dioxide. These enzymes are of ancient origin as they are found in the deepest of branches of the evolutionary tree. Of the five different classes of carbonic anhydrases, the alpha class has perhaps received the most attention because of its role in human pathology. This review focuses on the physiological function of this class of carbonic anhydrases organized by their cellular location.
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Affiliation(s)
- Susan C Frost
- Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, USA,
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Chung SS, Schusse C. Antiepileptic drugs. SIDE EFFECTS OF DRUGS ANNUAL 2014:133-169. [DOI: 10.1016/b978-0-444-62635-6.00007-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Traub RD, Cunningham MO, Whittington MA. What Is a Seizure Network? Very Fast Oscillations at the Interface Between Normal and Epileptic Brain. ISSUES IN CLINICAL EPILEPTOLOGY: A VIEW FROM THE BENCH 2014; 813:71-80. [DOI: 10.1007/978-94-017-8914-1_6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
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Siniscalchi A, Gallelli L, Russo E, De Sarro G. A review on antiepileptic drugs-dependent fatigue: pathophysiological mechanisms and incidence. Eur J Pharmacol 2013; 718:10-6. [PMID: 24051268 DOI: 10.1016/j.ejphar.2013.09.013] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2013] [Revised: 08/29/2013] [Accepted: 09/04/2013] [Indexed: 02/04/2023]
Abstract
Fatigue represents a common side effect of several drugs, however, the underlying mechanisms have not been well identified. A depression of the central nervous system (CNS) and/or changes in peripheral processes have been associated with the development of fatigue. Antiepileptic drugs (AEDs), generally decreasing CNS excitability, are used in the treatment of seizures as well as other neurological and psychiatric diseases. Fatigue is certainly a common AEDs' side effect, although a high degree of variability exists depending on both patients' characteristics and the drug used. Here, we delineate the pathophysiological central and peripheral mechanisms by which AEDs may cause fatigue also reviewing the available clinical data in order to assess a possible AEDs rank and highlight each AEDs related risk. It appears that drugs acting on the GABAergic system have the highest incidence (with tiagabine exception) of fatigue followed by Gabapentin and Levetiracetam whereas drugs mainly inhibiting sodium channels (Carbamazepine, Eslicarbazepine, Lamotrigine, Phenytoin and Valproate) have the lowest. However, the dose used, AEDs related side effects and patients' characteristics might influence the degree of fatigue observed.
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Affiliation(s)
- Antonio Siniscalchi
- Department of Neuroscience, Neurology Division, Annunziata Hospital, Cosenza, Italy
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Sato S, Nishinaka K, Takahashi S, Hirobe M, Tsukamoto T. [Bilateral urolithiasis with zonisamide developed for a short period of time in a 10-year-old girl with intractable epilepsy]. Nihon Hinyokika Gakkai Zasshi 2013; 104:674-677. [PMID: 24187857 DOI: 10.5980/jpnjurol.104.674] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/02/2023]
Abstract
Zonisamide is an antiepileptic drug mainly used in patients with refractory epilepsy. One of the urological adverse effects caused by zonisamide is urinary lithiasis. We reported bilateral urinary lithiasis with zonisamide developed for a short period of time. A 10 year-old girl had been treated with zonisamide for intractable epilepsy for nine years. She progressively developed microscopic hematuria as well as crystalluria while being hospitalized for ventriculoperitoneal shunt infection. A computed tomography (CT) showed bilaterally hydronephrotic kidneys obstructed by multiple ureteral calculi. What was impressive was the fact that any single urinary calculus was not identified in a CT image taken just three weeks prior to this event. Then the diagnosis was made of zonisamide-induced bilateral urinary calculi and zonisamide treatment was discontinued. However, since the deterioration of renal function and left-sided hydronephrosis progressed, we performed the construction of right-sided percutaneous nephrostomy (PNS) and the transurethral placement of a left ureteral stent. Subsequently her condition was stabilized and all of these stones were discharged. The analysis of these stones showed mainly calcium phosphatic calculus. We eventually removed both the right PNS and the left ureteral stent. Since then, there has not been any recurrence thus far. We need to recognize the risk of progressively developing renal calculi during zonisamide treatment for a relatively short period of time in the face of dehydration.
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Affiliation(s)
- Shunsuke Sato
- Department of Urology, Hokkaido Medical Center for Child Health and Rehabilitation.
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Aggarwal M, Kondeti B, McKenna R. Anticonvulsant/antiepileptic carbonic anhydrase inhibitors: a patent review. Expert Opin Ther Pat 2013; 23:717-24. [DOI: 10.1517/13543776.2013.782394] [Citation(s) in RCA: 155] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
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Mancuso M, Orsucci D, Filosto M, Simoncini C, Siciliano G. Drugs and mitochondrial diseases: 40 queries and answers. Expert Opin Pharmacother 2012; 13:527-43. [DOI: 10.1517/14656566.2012.657177] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Abtahi MA, Abtahi SH, Fazel F, Roomizadeh P, Etemadifar M, Jenab K, Akbari M. Topiramate and the vision: a systematic review. Clin Ophthalmol 2012; 6:117-31. [PMID: 22275816 PMCID: PMC3261698 DOI: 10.2147/opth.s27695] [Citation(s) in RCA: 70] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND AND PURPOSE Topiramate (TPM) is a sulfa-derivative monosaccharide that is used mainly for treating epilepsy and preventing migraine. Within the gamut of side effects attributable to this drug, ophthalmologic manifestations are of crucial importance. In this study, for the first time, the aim was to provide a systematic literature review regarding this issue. METHODS For the time period 1996-2011, a PubMed search was made for the studies concerning the adverse/beneficial effects of TPM on vision. Overall, 404 citations out of a total of 2756 TPM-related studies were examined for relevance. RESULTS A total of 74 relevant studies were reviewed, 65 of which comprise small observational studies describing the ophthalmic side effects of TPM in 84 patients. Of these patients, 66 were affected by ciliochoroidal effusion syndrome as the cardinal ocular side effect of TPM (17 cases of myopic shift and 49 cases of angle closure glaucoma). A comprehensive statistical analysis is provided on these 66 subjects. Other rare side effects of TPM on the vision were also reviewed, including massive choroidal effusion, ocular inflammatory reactions, visual field defects, probable effects on retina, cornea, and sclera, and neuroophthalmologic complications. In addition, a framework is provided to classify these results. DISCUSSION Due to the expanding spectrum of indications for the administration of TPM, neurologists and psychiatrists should be aware of its diverse ocular side effects. In conclusion, ocular complications following this drug should be taken seriously and be subjected to ophthalmic counseling.
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Affiliation(s)
- Mohammad-Ali Abtahi
- Medical School, Isfahan University of Medical Sciences, Isfahan, Iran
- Ophthalmology Ward, Feiz Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
- Isfahan Eye Research Center (IERC), Feiz Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Seyed-Hossein Abtahi
- Medical School, Isfahan University of Medical Sciences, Isfahan, Iran
- Isfahan Eye Research Center (IERC), Feiz Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
- Isfahan Medical Students Research Center (IMSRC), Isfahan University of Medical Sciences, Isfahan, Iran
| | - Farhad Fazel
- Ophthalmology Ward, Feiz Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
- Isfahan Eye Research Center (IERC), Feiz Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Peyman Roomizadeh
- Medical School, Isfahan University of Medical Sciences, Isfahan, Iran
- Isfahan Medical Students Research Center (IMSRC), Isfahan University of Medical Sciences, Isfahan, Iran
| | - Masoud Etemadifar
- Department of Neurology, Medical School, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Keivan Jenab
- Ophthalmology Ward, Feiz Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
- Isfahan Eye Research Center (IERC), Feiz Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mojtaba Akbari
- Medical School, Isfahan University of Medical Sciences, Isfahan, Iran
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