Indian Epilepsy Society Valproic Acid: Indian Consensus Document Editor-in-Chief Man Mohan Mehndiratta ELSEVIER Indian Epilepsy Society: Valproic Acid: Indian Consensus Document A division of Reed Elsevier India Private Limited © 2016 Indian Epilepsy Society. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the Publisher. Notices Knowledge and best practice in this fi eld are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. 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The Publisher ISBN 978-81-312-4628-3 Published by: Elsevier, a division of Reed Elsevier India Private Limited Registered Offi ce: 818, Indraprakash Building 21, Barakhamba Road, New Delhi-110001 Corporate Offi ce: 14th Floor, Tower 10B, DLF Cyber City, Phase-II, Gurgaon 122002, Haryana Typeset at ArtMart, Matunga (W), Mumbai Printed at ???????? ii Core Committee and Contributors Man Mohan Mehndiratta – Convener Sanjeev V. Th omas – Convener Director; Professor & Head, Professor of Neurology and Department of Neurology, Head of R. Madhavan Nayar Centre for Janakpuri Super Speciality Hospital, Comprehensive Epilepsy Care, New Delhi Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Th iruvananthapuram Neeraj N. Baheti Jayantee Kalita Consultant Neurologist and Epileptologist, Professor, Department of Neurology Central India Institute of Medical Sciences, Sanjay Gandhi Post Graduate medical Sciences, Nagpur 440010, Maharashtra Lucknow Atma Ram Bansal Parampreet S. Kharbanda Neurologist and Epileptologist, Additional Professor Neurology & In-charge Medanta—Th e Medicity Gurgaon, Comprehensive Epilepsy Program, Haryana Department of Neurology, Postgraduate Institute of Medical Education & Sanjeev Bhoi Research (PGIMER), Chandigarh Assistant Professor, Department of Neurology Sanjay Gandhi Post Graduate medical Sciences, Chanda Kulkarni Lucknow Advisor – Department of Clinical Pharmacology, SAKRA World Hospital; Bangalore, India Deepanshu Dubey Senior Resident, Department of Neurology Bindu Menon Sanjay Gandhi Post Graduate medical Sciences, Senior Consultant Neurologist, Lucknow Apollo Speciality Hospitals, Nellore Usha Kant Misra Sheff ali Gulati Professor & Head, Department of Neurology, Professor of Pediatrics, Sanjay Gandhi Post Graduate Institute of Chief of Child Neurology Division, Medical Sciences, Department of Pediatrics, Raebareli Road, Lucknow All India Institute of Medical Sciences, New Delhi P. Satishchandra Director/Vice Chancellor and Senior Professor of Satish Jain Neurology, National Institute of Mental Health & Director, Indian Epilepsy Centre, New Delhi Neuro Sciences (NIMHANS), Bengaluru, Karnataka Sita Jayalakshmi Senior Consultant Neurologist, Vinod S. Saxena Krishna Institute of Medical Sciences, Life Trustee Indian Epilepsy Association – Secunderabad, Telangana 18th International Epilepsy Congress Trust, Delhi iii Suvasini Sharma Sudhindra Vooturi Assistant Professor, Department of Neurology, Krishna Institute of Department of Pediatrics, Medical Sciences, Minister Road, Lady Hardinge Medical College and Secunderabad - 03, Telangana, Associated Kalawati Saran Children’s Hospital, India New Delhi Nandan Yardi Gagandeep Singh Consultant Epileptologist & Pediatric Neurologist Professor & Head, Associate Professor,Pediatrics , Department of Neurology, BJ MEDICAL COLLEGE(MUHS) Dayanand Medical College, Ludhiana Yardi Epilepsy & sleep clinic, Kothrud, Pune KEM hospital, Jehangir Hospital, Deenanath Sanjib Sinha Mangeshkar Hospital Pune Professor of Neurology, Member, Task force on pediatric NIMHANS, Banglore Epilepsy Surgery (2004-) Manjari Tripathi Member, ILAE Treatment Strategies Commission Professor, Department of Neurology, (2004-2009) Neurosciences Centre, All India Institute of Medical Sciences, New Delhi iv ELSEVIER INDIA CONTENT OPERATIONS Mr. Gaurav Bha a Mr. Sunil Kumar Dr. Atul Pa l Mr. Dhan Singh Dr. Nitendra Sesodia Mr. Ganesh Venkatesan EDITORIAL OFFICE Elsevier, a division of Reed Elsevier India Private Limited 14th Floor, Building No. 10B, DLF Cyber City, Phase-II, Gurgaon, Haryana – 122002, India. Telephone: + 91-124-4774444 Fax: + 91-124-4774100 v Contents Statement of Need and Introduction . 1 Historical Aspect of Valproic Acid . 3 Clinical Pharmacology of Valproic Acid . 9 Valproic Acid – Role in Idiopathic Generalized Epilepsy (IGEs) . 15 Valproic Acid in Focal Epilepsy . 21 Valproic Acid in Epileptic Syndromes with Special Reference to Juvenile Myoclonic Epilepsy . 23 Valproic Acid in Status Epilepticus . 25 Effi cacy of Valproic Acid – Comparison with Other Anti-Epileptic Drugs . 30 Valproic Acid – Adverse Eff ects and Tolerability Profi le . 34 Pharmacoeconomics of Valproic Acid . 42 Valproic Acid – A Paediatric Perspective . 43 Valproic Acid Use in Girls and Women with Epilepsy . 54 Valproic Acid in Epilepsy with Various Comorbidites and Systemic Disorders . 59 vi Statement of Need and Introduction Man Mohan Mehndiratt a Neurology, as a branch of medicine, is a society, the practitioners need to update themselves superspecialty that requires knowledge of a wide on the current approaches and the wide variety of range of clinical presentations. Because of the choices now available. India has a distinct need diversity of clinical conditions encountered and for comprehensive programs about the drugs and the modifi cation of the presentation of these at disease conditions that fi t into the Indian context various stages of growth and development, it takes of the situation. It has to be a continuous process longer to acquire the pattern recognition and to be that aims at updating the clinicians on the current able to recognize presentations of the common and scenario and clear the apprehensions based on rare conditions. Epilepsy is a common neurological scientifi c evidence and approaches the problem on disorder with 65 million People with Epilepsy (PWE) the basis of the experience of the specialists in India worldwide and approximately more than 12 million who are among the stalwarts in this fi eld. in India. Two-third of PWE live in resource-limited Th is document provides a useful basis from which countries. to view new and existing perspectives in usage and In this age, where at times there seems to be an position of Valproic Acid in the management of overabundance of information, it is important for epilepsy, coupled with the more traditional protocols. the practicing clinician to have an authoritative It will be a valuable update tool and reference point source of quality advice and genuine practice for the many professionals engaged in the fi eld of wisdom. Keeping in mind the requirements of the Neurology. 1 2 Historical Aspect of Valproic Acid Vinod Saxena Introduction Bromides came next. Th e Royal Medical and Chirurgical Society of London met under the Th e description of epilepsy dates back to antiquity. chairmanship of Sir Charles Locock then the Written texts have been found in Akkadian language obstetrician for Queen Victoria. He must have been in Mesopotamia in 2000 BC, in Sanskrit in Charaka very busy having delivered her nine children yet he Samhita in 600 BC, in the Greek classic On the presided over scientifi c meetings of consequence. Sacred Disease and in the Hippocratic collection of In one such meeting on 11th May 1857, Dr. Edward 1 medical writings in 400 BC. Shrouded as it has been Seiveking5 reported positive outcome with potassium in superstition, dogmatism, mysticism, or even star bromide in 52 women. Locock endorsed the idea for constellations, the treatments remained similarly treating more cases as he cited the observations of obscurantist. Alchemy