Drug Class Review Antiepileptic Drugs for indications other than Epilepsy Final Report Update 2 October 2008 Original Report Date: December 2004 Update 1 Report Date: May 2006 A literature scan of this topic is done periodically The purpose of this report is to make available information regarding the comparative effectiveness and safety profiles of different drugs within pharmaceutical classes. Reports are not usage guidelines, nor should they be read as an endorsement of, or recommendation for, any particular drug, use or approach. Oregon Health & Science University does not recommend or endorse any guideline or recommendation developed by users of these reports. Update 2 Marian Mcdonagh, PharmD. Kim Peterson, MS. Nancy Lee, PharmD. Sujata Thakurta, MPA:HA Oregon Evidence-based Practice Center Oregon Health & Science University Mark Helfand, MD, MPH, Director Original Report and Update 1 Southern California Evidence-based Practice Center RAND Paul Shekelle, MD, PhD, Director Copyright © 2008 by Oregon Health & Science University Portland, Oregon 97201. All rights reserved Note: A scan of the medical literature relating to the topic is done periodically (see http://www.ohsu.edu/ohsuedu/research/policycenter/DERP/about/methods.cfm for scanning process description). The Drug Effectiveness Review Project governance group elected to proceed with another update of this report based on the information contained in the scan. Please see timeline on the DERP website for details on the date of its release. Prior versions of this report can be accessed at the DERP website. Final Report Update 2 Drug Effectiveness Review Project TABLE OF CONTENTS INTRODUCTION ..........................................................................................................................5 Scope and Key Questions ......................................................................................................................10 METHODS ..................................................................................................................................11 Inclusion Criteria .....................................................................................................................................11 Study Designs.........................................................................................................................................12 Literature Search ....................................................................................................................................13 Study Selection.......................................................................................................................................13 Data Abstraction .....................................................................................................................................13 Quality Assessment ................................................................................................................................13 Data Synthesis........................................................................................................................................14 Meta-Analysis of Specific Adverse Events .............................................................................................15 Peer and Public Review..........................................................................................................................16 RESULTS ...................................................................................................................................17 Overview.................................................................................................................................................17 Summary of Findings..............................................................................................................................18 Bipolar Disorder..................................................................................................................................18 Fibromyalgia.......................................................................................................................................19 Migraine Prophylaxis ..........................................................................................................................19 Chronic Pain.......................................................................................................................................20 Harms Associated with Antiepileptic Drugs........................................................................................20 Subgroups ..........................................................................................................................................22 Detailed Assessment ..............................................................................................................................22 Key Question 1...................................................................................................................................22 Bipolar disorder ..............................................................................................................................22 Manic/mixed episodes ...............................................................................................................23 Hypomania.................................................................................................................................26 Maintenance of response: Manic/mixed episodes ....................................................................27 Acute bipolar depression ...........................................................................................................30 Maintenance of response: Bipolar depression ..........................................................................33 Maintenance of response: Rapid cycling...................................................................................34 Fibromyalgia...................................................................................................................................35 Acute treatment .........................................................................................................................35 Relapse......................................................................................................................................37 Migraine prophylaxis ......................................................................................................................38 Previous systematic review .......................................................................................................38 Additional trials ..........................................................................................................................39 Chronic pain ...................................................................................................................................42 Key Question 2...................................................................................................................................43 Suicide ...........................................................................................................................................43 Bone fractures................................................................................................................................44 Stevens-Johnson syndrome and toxic epidermal necrolysis.........................................................45 Aplastic anemia and agranulocytosis.............................................................................................45 Birth defects ...................................................................................................................................46 Polycystic ovary syndrome ............................................................................................................47 Delirium ..........................................................................................................................................47 Overall adverse event rates ...........................................................................................................47 Specific adverse events .................................................................................................................52 Key Question 3...................................................................................................................................53 Bipolar disorder ..............................................................................................................................53 Patient characteristics................................................................................................................53 Fibromyalgia...................................................................................................................................54 Antiepileptic drugs Page 2 of 117 Final Report Update 2 Drug Effectiveness Review Project Migraine prophylaxis ......................................................................................................................55 Chronic pain ...................................................................................................................................55 REFERENCES ...........................................................................................................................56 FIGURES Figure 1. Results of literature search (Update 2) .................................................................................17