Drug Class Review on Second Generation Antidepressants Final Report March 2006 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. Gerald Gartlehner, M.D., M.P.H. Richard A. Hansen, Ph.D. Leila Kahwati, M.D., M.P.H. Kathleen N. Lohr, Ph.D. Bradley Gaynes, M.D., M.P.H Tim Carey, M.D., M.P.H. Produced by RTI-UNC Evidence-based Practice Center Cecil G. Sheps Center for Health Services Research University of North Carolina at Chapel Hill 725 Airport Road, CB# 7590 Chapel Hill, NC 27599-7590 Tim Carey, M.D., M.P.H., Director Oregon Evidence-based Practice Center Oregon Health & Science University Mark Helfand, MD, MPH, Director Copyright © 2006 by Oregon Health & Science University Portland, Oregon 97201. All rights reserved. Final Report Update 2 Drug Effectiveness Review Project TABLE OF CONTENTS INTRODUCTION .......................................................................................................................................................5 OVERVIEW.................................................................................................................................................................5 SCOPE AND KEY QUESTIONS .....................................................................................................................................8 METHODS...................................................................................................................................................................9 LITERATURE SEARCH ................................................................................................................................................9 STUDY SELECTION...................................................................................................................................................10 DATA ABSTRACTION ...............................................................................................................................................11 QUALITY ASSESSMENT............................................................................................................................................11 DATA SYNTHESIS ....................................................................................................................................................12 RESULTS...................................................................................................................................................................13 OVERVIEW...............................................................................................................................................................13 KEY QUESTION 1: EFFICACY...............................................................................................................................15 I. Adult outpatients with depressive disorder (major depressive disorder and dysthymia subtypes) and pediatric outpatients with major depressive disorder........................................................................................15 A. Major Depressive Disorder in Adults......................................................................................................................... 15 1. SSRIs compared to SSRIs in adult outpatients with major depressive disorder..................................................... 16 2. Other second-generation antidepressants compared to SSRIs in adult outpatients with major depressive disorder...................................................................................................................................................................... 20 3. Summary of the evidence ...................................................................................................................................... 25 B. Dysthymia in Adults................................................................................................................................................... 33 1. SSRIs compared to placebo in adults with dysthymia ........................................................................................... 33 2. Summary of the evidence ...................................................................................................................................... 34 C. Major Depressive Disorder in Children and Adolescents........................................................................................... 35 1. SSRIs compared to placebo in pediatric outpatients with major depressive disorder ............................................36 2. SNRIs compared to placebo in pediatric outpatients with major depressive disorder............................................37 3. Systematic review of published and unpublished data comparing SSRIs and SNRIs to placebo in pediatric outpatients with major depressive disorder................................................................................................................ 38 4. Summary of the evidence ...................................................................................................................................... 38 II.Adult outpatients with anxiety disorders (generalized anxiety disorder, obsessive compulsive disorder, panic disorder, post-traumatic stress disorder, social anxiety disorder)...........................................................39 A. Generalized Anxiety Disorder.................................................................................................................................... 39 1. SSRIs compared to SSRIs in adult outpatients with GAD..................................................................................... 40 2. SSRIs compared to placebo in adult outpatients with GAD .................................................................................. 40 3. Summary of the evidence ...................................................................................................................................... 42 B. Obsessive-Compulsive Disorder ................................................................................................................................ 43 1. SSRIs compared to SSRIs in adult outpatients with OCD..................................................................................... 43 2. Other second-generation antidepressants compared to SSRIs in adult outpatients with OCD............................... 44 3. SSRIs augmentation compared to SSRI alone in adult outpatients with OCD....................................................... 44 4. SSRIs compared to placebo in adult outpatients with OCD................................................................................... 44 5. Summary of the evidence ...................................................................................................................................... 45 C. Panic Disorder........................................................................................................................................................... 46 1. SSRIs compared to SSRIs in adult outpatients with Panic Disorder...................................................................... 47 2. SSRIs compared to placebo in adult outpatients with Panic Disorder ................................................................... 47 3. Summary of the evidence ...................................................................................................................................... 48 D. Post-Traumatic Stress Disorder.................................................................................................................................. 49 1. SSRIs compared to other second-generation antidepressants in adult outpatients with PTSD .............................. 49 2. SSRIs compared to placebo in adult outpatients with PTSD ................................................................................. 50 3. Summary of the evidence ...................................................................................................................................... 51 E. Social Anxiety Disorder ............................................................................................................................................. 52 1. SSRIs compared to SSRIs in adult outpatients with social anxiety disorder.......................................................... 53 2. Other second-generation antidepressants compared to SSRIs in adult outpatients with social anxiety disorder.... 53 3. SSRIs compared to placebo in adult outpatients with social anxiety disorder ....................................................... 53 4. Summary of the evidence ...................................................................................................................................... 55 III. Adult outpatients with premenstrual dysphoric disorder or late luteal phase dysphoric disorder .............58 Second Generation Antidepressants Page 2 of 507 Final Report Update 2 Drug Effectiveness Review Project 1. SSRIs compared to placebo in adult outpatients with premenstrual dysphoric disorder or late luteal phase dysphoric disorder ....................................................................................................................................................