Drug Class Review Second-generation Antidepressants Final Update 5 Evidence Tables March 2011 The purpose of Drug Effectiveness Review Project reports is to make available information regarding the comparative clinical effectiveness and harms of different drugs. 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 4: October 2008 Update 3: September 2006 Update 2: March 2006 Update 1: July 2005 Original Report: November 2004 Gerald Gartlehner, M.D., M.P.H. Richard A. Hansen, Ph.D. Ursula Reichenpfader, MD, MPH Angela Kaminski, MD Christina Kien, MSc Michaela Strobelberger, MA Megan Van Noord, MSIS Patricia Thieda, MA Kylie Thaler, MD, MPH Bradley Gaynes, 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 Tim Carey, M.D., M.P.H., Director Drug Effectiveness Review Project Marian McDonagh, PharmD, Principal Investigator Oregon Evidence-based Practice Center Mark Helfand, MD, MPH, Director Copyright © 2011 by Oregon Health & Science University Portland, Oregon 97239. All rights reserved. The medical literature relating to this topic is scanned periodically. (See http://www.ohsu.edu/ohsuedu/research/policycenter/DERP/about/methods.cfm for description of scanning process). Prior versions of this report can be accessed at the DERP website. TABLE OF CONTENTS Abbreviations used in evidence tables ....................................................................................................... 4 Evidence Table 1. Major Depressive Disorder in Adults ............................................................................ 7 Evidence Table 2. Dysthymia ................................................................................................................ 190 Evidence Table 3. Subsyndromal Depression ....................................................................................... 202 Evidence Table 4. Seasonal Affective Disorder ..................................................................................... 206 Evidence Table 5. Major Depressive Disorder in Pediatrics .................................................................. 210 Evidence Table 6. General Anxiety Disorder ......................................................................................... 235 Evidence Table 7. Obsessive-compulsive Disorder .............................................................................. 254 Evidence Table 8. Panic Disorder .......................................................................................................... 274 Evidence Table 9. Post-Traumatic Stress Disorder ............................................................................... 288 Evidence Table 10. Social Anxiety Disorder .......................................................................................... 304 Evidence Table 11. Premenstrual Dysphoric Disorder .......................................................................... 329 Evidence Table 12. Adverse Events ...................................................................................................... 341 Evidence Table 13. Subgroups .............................................................................................................. 490 References ............................................................................................................................................. 593 Abbreviations used in evidence tables Abbreviation Term ACT Active-control trial AE Adverse event ANCOVA Analysis of covariance ANOVA Analysis of variance BDI II Beck Depression Inventory II Beck’s SSI Scale for Suicide Ideation bid Twice daily BMI Body mass index BQOL Battelle Quality of Life Measure CAPS Clinician Administered PTSD Scale CAS Clinical Anxiety Scale CCEI Crown Crisp Experiential Index CCT Controlled clinical trial CDRS Cornell Dysthymia Rating Scale CGI Clinical Global Impressions CGI – S Clinical Global Impressions Severity Scale CGI –I Clinical Global Impressions Improvement Scale CI Confidence interval (reported in the following format: 95% CI, xx to xx) CIS Clinical Interview Schedule CNS Central nervous system CR Controlled release CV Cardiovascular CVS Cardiovascular system d Day DB Double-blind dL Deciliter DSM – IV Diagnostic and Statistical Manual of Mental Disorders, version IV ECG Electrocardiogram EEG Electroencephalogram EF Ejection fraction ER Extended release ESRS Extrapyramidal Symptom Rating Scale FDA US Food and Drug Administration FSQ Functional Status Questionnaire FU Follow-up g Gram GHQ General Health Questionnaire GI Gastrointestinal GP General practitioner h Hour Abbreviation Term HAD Hospital Anxiety and Depression Rating Scale HADRS Hamilton Depression Rating Scale HAM – A Hamilton Rating Scale for Anxiety HAM – D Hamilton Rating Scale for Depression HDL-C High density lipoprotein cholesterol HMO HR Health maintenance organization Hazard ratio HRQOL Health related quality-of-life ICD-10 International Classification of Diseases, Tenth Revision ICD-9 International Classification of Diseases, Ninth Revision IDAS Irritability, depression, and anxiety scale IDS C Inventory for Depressive Symptomatology - Clinician Rated IDS SR Inventory for Depressive Symptomatology – Self Rated IR Immediate release ITT Intention-to-treat L Liter LA Long acting LDL-C Low-density lipoprotein cholesterol LOCF Last Observation Carried Forward LS means Least squares means MADRS Montgomery Asberg Depression Rating Scale MANCOVA Multivariate analysis of covariance mcg Microgram mg Milligram min Minute mL Milliliter MMSE Mini Mental State Examination mo Month MOCI Maudsley Obsessive Compulsive Inventory N Sample size (entire sample) n Subgroup sample size NA Not applicable NR Not reported NS Not significant NSD No significant difference OR Odds ratio P P value (uppercase and italicized, ie P=0189) P Placebo PAS Panic and Agoraphobia Scale PCT Placebo-controlled trial PGIS Patient Global Improvement Scale PPY Per person year PRIME MD Primary Care Evaluation of Mental Disorder Abbreviation Term PSE Present State Examination qd Once daily QLDS Quality of Life in Depression Scale QLSQ Quality of Life Enjoyment and Satisfaction Questionnaire QOL Quality-of-life RCIS Revised Clinical Interview Schedule—Shona Version RCT Randomized controlled trial RR Relative risk SADS Schedule for Affective Disorders and Schizophrenia SB Single-blind SCAG Sandoz Clinical Assessment Geriatric Scale SCID Structured Clinical Interview for DSM III Revised SCL 25 Hopkins Symptom Checklist 25 item version SD Standard deviation SDS Sheehan Disability Scale SDS Self rating Depression Scale SE Standard error SF-36 Medical Outcomes Study Health Survey - Short Form 36 Structured Interview Guide for the Hamilton Depression Rating Scale, Seasonal SIGH SAD Affective Disorders Version SIP Sickness Impact Profile SLT Shopping List Task SR Sustained release SSQ Shona Symptom Questionnaire tid Three times daily VAS Visual analog scale vs Compared with (versus) WD Withdrawal XR Extended release y Year Y-BOCS Yale Brown Obsessive Compulsive Scale Evidence Table 1 Major Depressive Disorder Adults STUDY: Authors: Aberg-Wistedt et al.1 Year: 2000 Country: Sweden FUNDING: Pfizer, Inc. DESIGN: Study design: RCT Setting: Multi-center Sample size: 353 INTERVENTION: Drug: Sertraline Paroxetine Dose: 50-150 mg/d 20-40 mg/d Duration: 24 weeks 24 weeks INCLUSION: Age 18 and over; met DSM-III-R criteria for MDD; MADRS score of > 21 at baseline with less than 25% improvement during washout EXCLUSION: Negative pregnancy test and stable use of oral contraceptive for 3 months; current or past history of mania; hypomania; alcoholism; substance abuse; dementia; epilepsy; presence of psychotic depression or organic affective illness; history of suicide attempts or high risk; current use of psychotropic meds; treatment with lithium or MAOI in the month prior to screening; history of intolerance or allergic reaction to either study drug; clinically evidence of hepatic or renal disease or other acute or unstable medical condition; use of any meds that would interfere with safe conduct of the study OTHER MEDICATIONS/ Nitrazepam, oxazepam, flunitrazepam INTERVENTIONS: POPULATION Groups similar at baseline: Yes CHARACTERISTICS: Mean age: 43 Gender (% Female): 67.4% Ethnicity: Not reported Other population characteristics: 8% over 65 years, 53% less than 45 years, 33% married or live with significant other Authors: Aberg-Wistedt et al. Year: 2000 Country: Sweden OUTCOME ASSESSMENT: Measures: MADRS, CGI-S, Secondary Battelle Quality of Life Measure (BQOL), SCID-II before and after treatment Timing of assessments: Primary measures at baseline and weeks 1, 2, 3, 4, 6, 8, 12,16, 20 and 24 RESULTS: Response-LOCF at 24 weeks: sertraline: 72%, paroxetine 69% Response-Observed Cases at 24 weeks: sertraline 89%, paroxetine 89% No significant difference at endpoint or at any other study point measures No significant difference in CGI severity change score or improvement score Relapse during weeks 9-24: paroxetine 8.6%, sertraline 1.9% (no p value reported) No significant differences on QOL measures ANALYSIS: ITT: LOCF Post randomization exclusions: Yes ATTRITION: Loss to follow-up: 35.4%; sertraline 36.4%, paroxetine 34.5% Withdrawals due to adverse events: Not reported