Drug Class Review on Pharmacologic Treatments for ADHD Final Report Update 2 November 2007 Original Report Date: August 2005 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. Marian S. McDonagh, PharmD Kim Peterson, MS Tracy Dana, MLS Sujata Thakurta, MPA:HA Oregon Evidence-based Practice Center Oregon Health & Science University Mark Helfand, MD, MPH, Director Copyright © 2007 by Oregon Health & Science University Portland, Oregon 97239. 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. 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 ..........................................................................................................................6 Scope and Key Questions ........................................................................................................................7 Inclusion Criteria .......................................................................................................................................8 Study Designs.........................................................................................................................................10 METHODS ..................................................................................................................................10 Literature Search ....................................................................................................................................10 Study Selection.......................................................................................................................................11 Data Abstraction .....................................................................................................................................11 Quality Assessment ................................................................................................................................11 Evidence Synthesis ................................................................................................................................12 RESULTS ...................................................................................................................................13 Overview.................................................................................................................................................13 Overall Summary of the Evidence on Efficacy or Effectiveness, Short-Term Efficacy and Tolerability, and Long-Term Safety of Drugs Used to Treat ADHD ...........................................................................16 General...............................................................................................................................................16 Young children (preschool age; 3-5 years) ........................................................................................17 Children (elementary school age; 6-12 years) ...................................................................................17 Adolescents ........................................................................................................................................20 Adults..................................................................................................................................................21 Subgroups ..........................................................................................................................................21 Key Question 1: What is the comparative efficacy or effectiveness of different pharmacologic treatments for attention deficit disorders? ..............................................................................................24 Young children (preschool age; 3-5 years) ........................................................................................24 Children (elementary school age; 6-12 years) ...................................................................................25 Generalizability issues ...................................................................................................................................25 Stimulants ......................................................................................................................................................25 Other stimulants.............................................................................................................................................36 Atomoxetine...................................................................................................................................................39 Functional outcomes: MPH IR .......................................................................................................................42 Adolescents (ages 13 to 17)...............................................................................................................43 Direct comparisons ........................................................................................................................................43 Indirect comparisons......................................................................................................................................44 Functional outcomes: MPH IR .......................................................................................................................44 Adults..................................................................................................................................................45 Direct comparisons ........................................................................................................................................45 Indirect comparisons......................................................................................................................................46 Key Question 2: Safety ...........................................................................................................................49 A. What is the comparative tolerability and safety of different pharmacologic treatments for attention deficit disorders? ................................................................................................................................49 Short-term trial evidence in young children (preschool age; 3-5 years) .........................................................49 Short-term trial evidence in children (elementary school age; 6-12 years) ....................................................50 Adolescents ...................................................................................................................................................53 Adults.............................................................................................................................................................53 B. What is the evidence of serious adverse effects associated with use of pharmacologic treatments for attention deficit disorders? ............................................................................................................55 Evidence on the long-term safety of drugs used to treat ADHD.....................................................................55 Height and weight effects...............................................................................................................................55 Tics ................................................................................................................................................................59 Seizures.........................................................................................................................................................60 Injuries ...........................................................................................................................................................60 Suicide...........................................................................................................................................................61 ADHD Page 2 of 132 Final Report Update 2 Drug Effectiveness Review Project Cardiovascular adverse events......................................................................................................................61 Hepatotoxicity ................................................................................................................................................63 C. Evidence on the risk of misuse or diversion of drugs used to treat ADHD in patients with no previous history of misuse/diversion ..................................................................................................63 Direct evidence ..............................................................................................................................................63