Major depressive disorder (MDD) is characterized by the occurrence of one or more major depressive episodes (MDEs), which persist for at least two weeks and are characterized by a depressed mood and/or markedly diminished interest or pleasure in all, or almost all, activities. The clinical manifestation of MDD is heterogeneous. The duration of MDEs can also vary significantly in duration, ranging from weeks to years. MDD is one of the most prevalent chronic conditions in Canada, with an annual prevalence reaching 4.8% and a lifetime prevalence of 10.8% of the population. The prevalence of MDD is twice as high for women as for men, but this difference declines with age. According to the Global Burden of Disease Study and other studies, MDD is a major cause of disability. Because of its early age of onset and frequent recurrences, MDD is also among the leading causes of disability, as measured by disability-adjusted life-years, worldwide.

The goal of treatment in patients with MDD is the resolution of symptoms (remission) in order to restore psychosocial and occupational functioning. Traditional antidepressant therapy (ADT) is the mainstay of treatment. Despite the availability of various ADTs, as many as 50% to 60% of patients do not respond to ADT.

Aripiprazole (Abilify) is an atypical antipsychotic (AAP) and is the only drug approved by Health Canada for the adjunctive treatment of MDD in adults who had an inadequate response to prior ADT. The objective of this review is to evaluate the beneficial and harmful effects of aripiprazole (oral tablets 2 mg, 5 mg, 10 mg, and 15 mg) as an adjunct to ADT for the treatment of MDD in adult patients who had an inadequate response to prior ADT during the current episode.

Contents

• Clinical Review Report
  • ABBREVIATIONS
  • EXECUTIVE SUMMARY
    • Introduction
    • Results and Interpretation
    • Pharmacoeconomic Summary
    • Results of Manufacturer’s Analysis
    • Interpretations and Key Limitations
    • Results of CADTH Common Drug Review Analysis
    • Conclusions
  • 1. INTRODUCTION
    • 1.1. Disease Prevalence and Incidence
    • 1.2. Standards of Therapy
    • 1.3. Drug
  • 2. OBJECTIVES AND METHODS
    • 2.1. Objectives
    • 2.2. Methods
  • 3. RESULTS
    • 3.1. Findings From the Literature
    • 3.2. Included Studies
    • 3.3. Patient Disposition
    • 3.4. Exposure to Study Treatments
    • 3.5. Critical Appraisal
    • 3.6. Efficacy
    • 3.7. Harms
  • 4. DISCUSSION
    • 4.1. Summary of Available Evidence
    • 4.2. Interpretation of Results
  • 5. CONCLUSIONS
  • APPENDIX 1. PATIENT INPUT SUMMARY
    • 1. Brief Description of Patient Group(s) Supplying Input
    • 2. Condition- and Current Therapy-Related Information
    • 3. Related Information About the Drug Being Reviewed
  • APPENDIX 2. LITERATURE SEARCH STRATEGY
  • APPENDIX 3. EXCLUDED STUDIES
  • APPENDIX 4. DETAILED OUTCOME DATA
  • APPENDIX 5. VALIDITY OF OUTCOME MEASURES
    • Aim
    • Findings
    • Hamilton Rating Scale for Depression
    • Montgomery–Åsberg Depression Rating Scale
    • Inventory of Depressive Symptomatology–Self-Report and Quick Inventory of Depressive Symptomatology–Self-Report
    • Clinical Global Impression–Severity of Illness and −Improvement
    • Sheehan Disability Scale
    • Quality of Life Enjoyment and Satisfaction Questionnaire
  • APPENDIX 6. SUMMARY OF OTHER STUDIES
    • Objective
    • Methods
    • Results
    • Interpretation
    • Conclusion
  • APPENDIX 7. SUMMARY OF COMPARATORS
    • Objective
    • Findings
    • Discussion
    • Critical Appraisal
    • Summary
    • Summary of Network Meta-analysis
    • Network Meta-analysis and Systematic Review
    • Study and Patient Characteristics
    • Results of the Network Meta-Analysis
    • Critical Appraisal of Network Meta-Analysis
    • Strengths
    • Limitations
    • Summary
  • REFERENCES
• Pharmacoeconomic Review Report
  • ABBREVIATIONS
  • EXECUTIVE SUMMARY OF THE PHARMACOECONOMIC SUBMISSION
    • Background
    • Summary of Economic Analysis
    • Results of Manufacturer’s Analysis
    • Interpretations and Key Limitations
    • Results of CADTH Common Drug Review Analysis
    • Issues for Consideration
    • Conclusions
  • 1. INTRODUCTION
    • 1.1. Study Question
    • 1.2. Treatment
    • 1.3. Comparators
    • 1.4. Type of Economic Evaluation
    • 1.5. Population
  • 2. METHODS
    • 2.1. Model Structure
    • 2.2. Clinical Inputs
  • 3. RESULTS
    • 3.1. Manufacturer’s Base Case
    • 3.2. Summary of the Manufacturer’s Sensitivity Analyses
    • 3.3. CADTH Common Drug Review Analyses
  • 4. DISCUSSION
    • 4.1. Issues for Consideration
    • 4.2. Patient Input
  • 5. CONCLUSIONS
  • APPENDIX 1. COST COMPARISON TABLE FOR DRUGS FOR MAJOR DEPRESSIVE DISORDER
  • APPENDIX 2. SUMMARY OF KEY OUTCOMES
  • APPENDIX 3. ADDITIONAL INFORMATION
  • REFERENCES
• CDEC FINAL RECOMMENDATION
  • Recommendation
  • Reasons for the Recommendation
  • Background
  • Summary of CDEC Considerations
  • Patient Input Information
  • Clinical Trials
  • Outcomes
  • Cost and Cost-Effectiveness
  • Other Discussion Points
  • Research Gaps

This report was prepared by the Canadian Agency for Drugs and Technologies in Health (CADTH). Through the CADTH Common Drug Review (CDR) process, CADTH undertakes reviews of drug submissions, resubmissions, and requests for advice, and provides formulary listing recommendations to all Canadian publicly funded federal, provincial, and territorial drug plans, with the exception of Quebec.

The report contains an evidence-based clinical and/or pharmacoeconomic drug review, based on published and unpublished material, including manufacturer submissions; studies identified through independent, systematic literature searches; and patient-group submissions. In accordance with CDR Update — Issue 87, manufacturers may request that confidential information be redacted from the CDR Clinical and Pharmacoeconomic Review Reports.

The information in this report is intended to help Canadian health care decision-makers, 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 with 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 document to ensure that its contents are accurate, complete, and up-to-date as of the date of publication, CADTH does not make any guarantee to that effect. CADTH is not responsible for the quality, currency, propriety, accuracy, or reasonableness of any statements, information, or conclusions contained in the source documentation. CADTH is not responsible for any errors or omissions or injury, loss, or damage arising from or relating to the use (or misuse) of any information, statements, or conclusions contained in or implied by the information in this document or in any of the source documentation.

This document is intended for use in the context of the Canadian health care system. Other health care systems are different; the issues and information related to the subject matter of this document may be different in other jurisdictions and, if used outside of Canada, it is at the user’s risk. This disclaimer and any questions or matters of any nature arising from or relating to the content or use (or misuse) of this document will be governed by and interpreted in accordance with the laws of the Province of Ontario and the laws of Canada applicable therein, and all proceedings shall be subject to the exclusive jurisdiction of the courts of the Province of Ontario, Canada.

CADTH takes sole responsibility for the final form and content of this document, subject to the limitations noted above. The statements and conclusions in this document are those of CADTH and not of its advisory committees and reviewers. The statements, conclusions, and views expressed herein do not necessarily represent the views of Health Canada or any Canadian provincial or territorial government. Production of this document is made possible by financial contributions from Health Canada and the governments of Alberta, British Columbia, Manitoba, New Brunswick, Newfoundland and Labrador, Northwest Territories, Nova Scotia, Nunavut, Ontario, Prince Edward Island, Saskatchewan, and Yukon.