Comparative Effectiveness Review Number 39 First- and Second- Generation Antipsychotics for Children and Young Adults Comparative Effectiveness Review Number 39 First- and Second-Generation Antipsychotics for Children and Young Adults Prepared for: Agency for Healthcare Research and Quality U.S. Department of Health and Human Services 540 Gaither Road Rockville, MD 20850 www.ahrq.gov Contract No. 290-2007-10021 Prepared by: University of Alberta Evidence-based Practice Center Edmonton, Alberta, Canada Research Team: Jennifer C. Seida, M.P.H. Janine R. Schouten, B.Sc. Shima S. Mousavi, M.D. Michele Hamm, M.Sc. Amy Beaith, M.I.St. Ben Vandermeer, M.Sc. Donna M. Dryden, Ph.D. Clinical Investigators: Khrista Boylan, M.D., FRCPC Amanda S. Newton, R.N., Ph.D. Normand Carrey, M.D., FRCPC, ABPN AHRQ Publication No. 11(12)-EHC077-EF February 2012 This report is based on research conducted by the University of Alberta Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290-2007-10021). The findings and conclusions in this document are those of the author(s), who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ. Therefore, no statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services. The information in this report is intended to help clinicians, employers, policymakers, and others make informed decisions about the provision of health care services. This report is intended as a reference and not as a substitute for clinical judgment. This report may be used, in whole or in part, as the basis for the development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products or actions may not be stated or implied. This document is in the public domain and may be used and reprinted without permission except those copyrighted materials that are clearly noted in the document. Further reproduction of those copyrighted materials is prohibited without the specific permission of copyright holders. Persons using assistive technology may not be able to fully access information in this report. For assistance, contact [email protected]. None of the investigators have any affiliations or financial involvement that conflicts with the material presented in this report. Suggested Citation: Seida JC, Schouten JR, Mousavi SS, Hamm M, Beaith A, Vandermeer B, Dryden DM, Boylan K, Newton AS, Carrey N. First- and Second-Generation Antipsychotics for Children and Young Adults. Comparative Effectiveness Review No. 39. (Prepared by the University of Alberta Evidence-based Practice Center under Contract No. 290-2007-10021.) AHRQ Publication No. 11(12)-EHC077-EF. Rockville, MD. Agency for Healthcare Research and Quality. February 2012. ii Preface The Agency for Healthcare Research and Quality (AHRQ) conducts the Effective Health Care Program as part of its mission to organize knowledge and make it available to inform decisions about health care. As part of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003, Congress directed AHRQ to conduct and support research on the comparative outcomes, clinical effectiveness, and appropriateness of pharmaceuticals, devices, and health care services to meet the needs of Medicare, Medicaid, and the Children’s Health Insurance Program (CHIP). AHRQ has an established network of Evidence-based Practice Centers (EPCs) that produce Evidence Reports/Technology Assessments to assist public- and private-sector organizations in their efforts to improve the quality of health care. The EPCs now lend their expertise to the Effective Health Care Program by conducting comparative effectiveness reviews (CERs) of medications, devices, and other relevant interventions, including strategies for how these items and services can best be organized, managed, and delivered. Systematic reviews are the building blocks underlying evidence-based practice; they focus attention on the strength and limits of evidence from research studies about the effectiveness and safety of a clinical intervention. In the context of developing recommendations for practice, systematic reviews are useful because they define the strengths and limits of the evidence, clarifying whether assertions about the value of the intervention are based on strong evidence from clinical studies. For more information about systematic reviews, see www.effectivehealthcare.ahrq.gov/reference/purpose.cfm. AHRQ expects that CERs will be helpful to health plans, providers, purchasers, government programs, and the health care system as a whole. In addition, AHRQ is committed to presenting information in different formats so that consumers who make decisions about their own and their family’s health can benefit from the evidence. Transparency and stakeholder input from are essential to the Effective Health Care Program. Please visit the Web site (www.effectivehealthcare.ahrq.gov) to see draft research questions and reports or to join an e-mail list to learn about new program products and opportunities for input. Comparative Effectiveness Reviews will be updated regularly. We welcome comments on this CER. They may be sent by mail to the Task Order Officer named below at: Agency for Healthcare Research and Quality, 540 Gaither Road, Rockville, MD 20850, or by email to [email protected]. Carolyn M. Clancy, M.D. Stephanie Chang M.D., M.P.H. Director Director, EPC Program Agency for Healthcare Research and Quality Center for Outcomes and Evidence Agency for Healthcare Research and Quality Jean Slutsky, P.A., M.S.P.H. Director, Center for Outcomes and Evidence Sonia Tyutyulkova, M.D., Ph.D. Agency for Healthcare Research and Quality Task Order Officer Center for Outcomes and Evidence Agency for Healthcare Research and Quality iii Acknowledgments The authors gratefully acknowledge the following individuals for their contributions to this project: Kenneth Bond (data extraction, quality assessment, and copy editing), Tamara Durec (peer review of literature search strategies), and Andrea Milne (data extraction, quality assessment, and table of outcome measures). We thank Christine Ha, Elizabeth Sumamo, and Kai Wong for help in screening the grey literature. Technical Expert Panel Dr. Jana Davidson Clinical Associate Professor of Psychiatry Dr. Dina Panagiotopoulos University of British Columbia Assistant Professor Vancouver, BC Division of Endocrinology Department of Pediatrics Dr. Fay Kagan University of British Columbia Pediatric/Adolescent Psychiatrist Vancouver, BC Hathaway-Sycamore Child and Family Services Pacoima, CA Dr. Adelaide S. Robb Associate Professor Dr. Syed Naqvi Psychiatry and Behavioral Sciences and Director Pediatrics Pediatric Psychopharmacology Clinic School of Medicine and Health Sciences Cedars-Sinai Medical Center George Washington University Los Angeles, CA Washington, DC Peer Reviewers Dr. Roberto Sassi Assistant Professor Department of Psychiatry and Behavioral Neuroscience McMaster University Hamilton, ON, Canada Dr. Fay Kagan Pediatric/Adolescent Psychiatrist Hathaway-Sycamore Child and Family Services Pacoima, CA Dr. Adelaide S. Robb Associate Professor Psychiatry and Behavioral Sciences and Pediatrics School of Medicine and Health Sciences George Washington University Washington, DC iv First- and Second-Generation Antipsychotics for Children and Young Adults Structured Abstract Objectives. To review and synthesize the evidence on first-generation antipsychotics (FGA) and second-generation antipsychotics (SGA) for the treatment of various psychiatric and behavioral conditions in children, adolescents, and young adults (ages ≤ 24 years). Data Sources. We conducted comprehensive searches in 10 electronic databases from 1987 to February 2011. We searched the grey literature, trial registries, and reference lists. Methods. Two reviewers conducted study selection and quality assessment independently and resolved discrepancies by consensus. One reviewer extracted data, and a second reviewer verified the data. We conducted a descriptive analysis for all studies and performed meta- analyses when appropriate. Results. Eighty-one studies (64 trials and 17 cohort studies) examined the following conditions: pervasive developmental disorders (12 studies); attention deficit hyperactivity disorder (ADHD) or disruptive behavior disorders (8 studies); bipolar disorder (11 studies); schizophrenia and related psychosis (31 studies); Tourette syndrome (7 studies); behavioral issues (4 studies); and multiple conditions (9 studies). One study reported data on both bipolar disorder and schizophrenia. The majority of the trials had a high risk of bias. The methodological quality of the cohort studies was moderate. Results are presented by outcome below. Symptoms: The strength of evidence for all head-to-head comparisons of FGAs and SGAs was low or insufficient to draw conclusions. SGAs were favored over placebo for behavior symptoms (ADHD and disruptive behavior disorders), the Clinical Global Impressions scale (ADHD and disruptive behavior disorders, bipolar disorder, and schizophrenia), positive and negative symptoms (schizophrenia), and tics (Tourette syndrome) (moderate strength of evidence). Other short- and long-term outcomes: All head-to-head comparisons had low or insufficient strength