MedicalResearch.com Interview with:
Emma Maund, MSc PhD
Nordic Cochrane Centre
MedicalResearch.com: What is the background for this study?
Response: Duloxetine has been approved in Europe for the treatment of stress urinary incontinence in women. It is not approved for this indication in the US and Canada. Currently, reasons why marketing authorization applications are withdrawn or denied are not published by either the Canadian or the US drug agency. However, the FDA has said that a higher-than-expected rate of suicide attempts – 2.6 timer higher – was observed in the open-label extensions of controlled trials of duloxetine for stress urinary incontinence. Given the FDA’s statement about the rate of suicide attempts, we wanted to determine whether duloxetine increased the risk of suicidality, violence or their possible precursors (drug induced akathisia, an extreme type of restlessness; activation, which consists of stimulating effects such as insomnia, anxiety and agitation; emotional disturbance, such as depersonalization and derealization; or psychotic events, such as delusions and hallucinations) in the randomized phases of the trials.
We therefore assessed the benefits and harms of duloxetine in stress urinary incontinence using clinical study reports, including individual patient data, of the 4 main trials submitted by Eli Lilly to the European Medicines Agency.
MedicalResearch.com: What are the main findings?
Response: Duloxetine was significantly better than placebo in terms of percentage change in weekly incontinence episodes (mean difference –13.56%, 95% confidence interval [CI] –21.59% to –5.53%) and change in Incontinence Quality of Life total score (mean difference 3.24, 95% CI 2.00 to 4.48). However, the effect sizes were small, and could be fully explained by unblinding bias. A sensitivity analysis (with removal of one trial) showed that the number needed to treat for a Patient Global Impression of Improvement rating of “much better or very much better” was 8 (95% CI 6 to 13). The numbers needed to harm were 7 (95% CI 6 to 8) for discontinuing because of an adverse event and 7 (95% CI 6 to 9) for experiencing an activation event. No suicidality, violence or akathisia events were noted.
MedicalResearch.com: What should readers take away from your report?
Response: For the treatment of stress urinary incontinence in women, the harms of duloxetine outweigh the potential benefits.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: As we have shown in this study, and previously, individual patient data contained in appendices of clinical study reports are essential for reliable assessment of drug harms. Researchers performing systematic reviews of drugs should therefore use clinical study reports as a primary data source if they are available.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Emma Maund, Louise Schow Guski , and Peter C. Gøtzsche
Considering benefits and harms of duloxetine for treatment of stress urinary incontinence: a meta-analysis of clinical study reportsCMAJ cmaj.151104; published ahead of print November 14, 2016,doi:10.1503/cmaj.151104
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