Efficacy and Safety of Risperidone and Paliperdone in Schizophrenia and Bipolar patients

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review


Background: Risperidone and Paliperidone are two mainstay anti-psychotic drugs approved for treating schizophrenia in adults and adolescents, and for the short-term treatment of manic or mixed episodes of bipolar disorder. However, over the last decade, the manufacturers have been involved in a rising number of legal (lawsuit) cases because they failed to disclose that the drug may cause hormonal imbalances that could lead to breast tissue development (‘Gynecomastia’) and infertility in boys and girls.

Objectives: As part of the Cochrane Clinical Study Report Working Group, we aim to systematically review all available evidence of the anti-psychotic drugs ‘Risperidone’ and 'Paliperidone' to assess whether they increases the risks of ‘Gynecomastia’, 'Cerebrovascular' and other SAEs in patients with schizophrenia or bipolar disorder. The review will utilise unpublished data sources including clinical study reports (CSRs) at the YODA project and the European Medicines Agency.

Methods: We have access to relevant randomised placebo-controlled trials at YODA, and further requests are being made to identify other sources of unpublished trials. Because of the novelty and size of CSRs, we will subdivide the extraction, appraisal, and analysis of the data into two stages. In stage 1, we assess the reliability and completeness of the identified trial data in a 'scoping review'. This will allow us to identify missing important text or data, and aid us in determining the completeness of the relevant parts of CSRs. Data will only be included in stage 2 (meta-analysis) if they satisfy the following three criteria, i) Completeness - they provided adequate information on harms according to our bespoke checklist, ii) Internal consistency - all parts of the same CSRs are consistent, iii) external consistency - consistency of data as reported in regulatory documents established by cross-checking.

Results: 55 Risperidone and 31 Paliperidone (palmitate) placebo-RCTs were eligible. 18 of the Risperidone and 22 Paliperidone trials have been obtained from YODA, where both the full CSRs and patient-listings data were retrieved. Further requests have been made at the EMA. On average only 16% of AEs and 23% of SAEs were reported in the journal publications compared to the CSRs and patient safety listing. Patient safety narratives were only provided in 10 (25%) of the CSRs, meaning information on the nature, timing and causality were difficult to determine. Redaction were also recorded.

Conclusions: We provide a comprehensive and rigorous assessment of the safety of two major anti-psychotic drugs for treating schizophrenia and bipolar diagnosed patients. The review is the first to involve unpublished data from CSRs and patient-safety listings and will influence current clinical guidance in this high-priority mental health area.

Patient or healthcare consumer involvement: An advisory group will be setup with PRIMER at the UoM to provide advice regarding patient safety concerns and to discuss the overall study findings and implications.
Original languageEnglish
Title of host publication27th Cochrane Colloquium
Subtitle of host publicationAdvances in Evidence Synthesis
Publication statusE-pub ahead of print - 30 Sept 2020


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