Schizophrenia is a chronic mental illness that requires lifelong treatment.^1,2 Patients with schizophrenia are at an increased risk for numerous other medical illnesses, including suicide.¹ In Canada, the disease affects about 1% of the population,² or about 234,000 people (2004 data).³ Antipsychotic medications form the cornerstone of treatment for schizophrenia.^2,4 Existing antipsychotic therapies fall into one of two classes: typical antipsychotics (TAP) and atypical antipsychotics (AAP). Both classes are considered equally effective in the treatment of positive symptoms. AAPs appear to be more effective in the treatment of negative symptoms.¹ TAPs are associated with an increased incidence of adverse events (AEs) known as extrapyramidal symptoms (EPS);¹ however, AAPs are associated with an increased risk of weight gain and metabolic AEs.¹

Treatment of schizophrenia is typically divided into three phases: acute, stabilization, and maintenance. In the acute phase, the patient routinely experiences psychotic symptoms, with pharmacotherapy being initiated or adjusted as soon as possible.^5,6 The role of antipsychotic maintenance medication in symptom control and the prevention of relapse of schizophrenia is well established. The underlying principles, when considering pharmacotherapy, include the individualization of medication (including patient preferences), uncomplicated medication regimens, appropriate dosing, regular evaluation of responses in general (including AEs), and short- and long-term clinical efficacy and safety.

Aripiprazole prolonged release suspension for injection (Abilify Maintena, 300 mg or 400 mg intramuscularly [IM] monthly), an AAP, is approved by Health Canada for the maintenance treatment of schizophrenia in stabilized adult patients. The objective of this report is to evaluate the beneficial and harmful effects of aripiprazole IM for the maintenance treatment of schizophrenia in stabilized adult patients.

Contents

• Clinical Review Report
  • ABBREVIATIONS
  • EXECUTIVE SUMMARY
    • Introduction
    • Results and Interpretation
    • 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
    • Psychotic Disorder Scales
    • Mental Health Status and Functioning
    • Adverse Events: Extrapyramidal Symptoms
    • A brief description of other scales used in the included trials
    • Conclusion
  • APPENDIX 6. SUMMARY OF OTHER STUDIES
    • Study Characteristics
    • Study Design
    • Efficacy
    • Safety
    • Critical Appraisal
    • Conclusions
  • APPENDIX 7. SUMMARY OF MANUFACTURER-SUBMITTED MIXED TREATMENT COMPARISON
    • Summary of network meta-analysis
    • Methods
    • Results
    • Results of the Meta-Analysis
    • Critical Appraisal of Network Meta-Analysis
    • Summary
  • REFERENCES
• Pharmacoeconomic Review Report
  • ABBREVIATIONS
  • SUMMARY
  • REVIEW OF THE PHARMACOECONOMIC SUBMISSION
  • 1. INTRODUCTION
    • 1.1. Cost Comparison Table
  • 2. SUMMARY OF PHARMACOECONOMIC SUBMISSION
  • 3. KEY LIMITATIONS
    • Clinical similarity to other LAIs uncertain
    • Key comparators omitted
    • Updated comparator pricing available
    • “Real-world” multivariate assumptions and sources
  • 4. ISSUES FOR CONSIDERATION
  • 5. CONCLUSIONS
  • APPENDIX 1. CADTH COMMON DRUG REVIEW REANALYSIS OF FREQUENCY OF ADMINISTRATION OF PALIPERIDONE AND RISPERIDONE LAI
  • APPENDIX 2. PRICE REDUCTION SCENARIOS
  • REFERENCES
• CDEC FINAL RECOMMENDATION
  • Recommendation
  • Reasons for the Recommendation
  • Background
  • Summary of CDEC Considerations
  • Other Discussion Points
  • Research Gaps

This review report was prepared by the Canadian Agency for Drugs and Technologies in Health (CADTH). In addition to CADTH staff, the review team included a clinical expert in psychiatry who provided input on the conduct of the review and the interpretation of findings.

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.