The objective of this study was to identify and appraise the clinical evidence pertaining to use of atypical antipsychotics (AAP) combination therapy and high-dose treatment strategies in adolescents and adults with schizophrenia.

Contents

• Contributors from CADTH
• Canadian Optimal Medication Prescribing and Utilization Service (COMPUS) Expert Review Committee
• Abbreviations
• 1. INTRODUCTION
  • 1.1 The COMPUS Expert Review Committee
• 2. ISSUE
  • Schizophrenia
  • Management of Schizophrenia
  • Technology Description — Atypical Antipsychotics
• 3. OBJECTIVES
  • 3.1 Project Overview
  • 3.2 Research Questions
• 4. METHODS
  • 4.1 Selection Criteria
  • 4.2 Inclusion criteria
  • 4.3 Exclusion criteria
  • 4.4 Quality Assessment and Data Extraction
  • 4.5 Data synthesis and analysis
• 5. RESULTS
  • 5.1 Selection of Primary Studies
  • 5.2 Study Characteristics
  • 5.3 Study Quality
  • 5.4 Overview of Clinical Analysis
  • 5.5 Clozapine-based antipsychotic combination therapy versus clozapine-monotherapy standard dose
  • 5.6 Non-clozapine antipsychotic combination therapy versus non-clozapine monotherapy
  • 5.7 High-dose non-clozapine AAP therapy versus standard-dose clozapine
  • 5.8 High-dose non-clozapine AAP versus standard-dose non-clozapine APD
  • 5.9 Evidence on clozapine-combination versus clozapine-combination AAP therapies
  • 5.10 Effect of AAP combination or high-dose AAP therapies on cognitive function
  • 5.11 Additional Evidence on the Safety of Combination and High-Dose Therapy
  • 5.12 Results from studies identified in literature alerts
• 6. DISCUSSION
  • 6.1 Summary of Main Findings
  • 6.2 Strengths and Weaknesses of Review
  • 6.3 Generalizability of Findings
• 7. CONCLUSIONS
• REFERENCES
• APPENDIX 1 LITERATURE SEARCH STRATEGY
• APPENDIX 2 SUMMARY OF OUTCOMES AS RANKED BY MEMBERS OF COMPUS EXPERT REVIEW COMMITTEE
• APPENDIX 3 VALIDITY OF PSYCHIATRIC SYMPTOM SCALES AND CLINICAL IMPLICATIONS
• APPENDIX 4 FOREST PLOTS FROM RANDOM EFFECTS META-ANALYSIS (REFERENCE CASE ANALYSES AND SUBGROUPS BY DRUG)
• APPENDIX 5 RESULTS OF SUBGROUP AND SENSITIVITY ANALYSES
• APPENDIX 6 LIST OF INCLUDED RCTS
• APPENDIX 7 LIST OF EXCLUDED STUDIES
• APPENDIX 8 LIST OF RCTS REPORTED IN MULTIPLE PUBLICATIONS
• APPENDIX 9 INCLUSION AND EXCLUSION CRITERIA REPORTED IN INCLUDED RCTS
• APPENDIX 10 STUDY LEVEL DEFINITION OF "INADEQUATE RESPONSE" TO APD TREATMENT IN INCLUDED RCT
• APPENDIX 11 DEFINITION OF RESPONSE TO ANTIPSYCHOTIC DRUG TREATMENT REPORTED IN INCLUDED RCTS
• APPENDIX 12 STUDY CHARACTERISTICS OF INCLUDED STUDIES
• APPENDIX 13 PATIENT CHARACTERISTICS OF INCLUDED STUDIES
• APPENDIX 14 QUALITY ASSESSMENT OF RCTS
• APPENDIX 15 DEFINITION OF SAE REPORTED IN INCLUDED RCTS
• APPENDIX 16 COGNITION DATA
• APPENDIX 17 SUPPLEMENTAL SAFETY REVIEW
• APPENDIX 18 SUMMARY OF INCLUDED STUDIES NOT INCLUDED IN THE REFERENCE CASE META-ANALYSES

This report is prepared by the Canadian Agency for Drugs and Technologies in Health (CADTH). This report contains a review of existing public literature, studies, materials, and other information and documentation (collectively the “source documentation”) available to CADTH at the time it was prepared, and it was guided by expert input and advice throughout its preparation.

The information in this report is intended to help health care decision-makers, patients, health care professionals, health systems leaders, and policy-makers make well-informed decisions and thereby improve the quality of health care services. The information in this report should not be used as a substitute for the application of clinical judgment in respect to the care of a particular patient or other professional judgment in any decision-making process, nor is it intended to replace professional medical advice. While CADTH has taken care in the preparation of this report to ensure that its contents are accurate, complete, and up-to-date, CADTH does not make any guarantee to that effect. CADTH is not responsible for any errors or omissions or injury, loss, or damage arising from or as a result of the use (or misuse) of any information contained in or implied by the information in this report.

CADTH takes sole responsibility for the final form and content of this report. The statements, conclusions, and views expressed herein do not necessarily represent the view of Health Canada or any provincial or territorial government.

Production of this report is made possible through a financial contribution from Health Canada.