Considering benefits and harms of duloxetine for treatment of stress urinary incontinence: a meta-analysis of clinical study reports

Abstract

The European Medicines Agency makes clinical study reports publicly available and publishes reasons for not approving applications for marketing authorization. Duloxe tine has been approved in Europe for the treatment of stress urinary incontinence in women. The reported adverse effects of duloxe tine include mental health problems and suicidality. We obtained clinical study reports from the European Medicines Agency concerning use of this drug for stress urinary incontinence.

Evaluation of the potentiating effects of antidepressants on the contractile response to noradrenaline in guinea pig urethra smooth muscles

“…However, duloxetine, an SNRI, improves stress urinary incontinence by increasing contractility of the external urinary sphincter muscle around the urethra through pudendal nerve activation, which is produced by increased serotonin and NA concentrations at the micturition reflex centre . Therefore, duloxetine is marketed as a remedy for stress urinary incontinence in several European countries …”

Likelihood of Being Helped or Harmed as a Measure of Clinical Outcomes in Psychopharmacology

“…5 As another example, data from a meta-analysis of 4 regulatory RCTs of duloxetine (80 mg/day) for stress urinary incontinence yielded LHH values of approximately 1; that is, for every extra woman who benefited (operationalized as a patient rating of much or very much better), 1 extra woman discontinued due to adverse events, and for every extra woman who benefited, 1 extra woman had problematic, activation-related adverse effects. 6 An earlier and briefer discussion on LHH was provided by Akobeng. …”

Secrecy or transparency? The future of regulatory trial data

“…This situation again shows the potential value of data held by regulatory agencies and confirms the findings of previous research: clin ical study reports contain an abundance of information, including substantially more information relevant for trial evaluation than is available in journal publications and registry reports. 5,6 Interestingly, the conclusion of the authors of the linked study 1 contrasts with that of the EMA, even though the two assessments were based on the same evidence. The EMA concluded that duloxetine has a positive benefit-risk ratio for stress urinary incontinence, 7 …”

“…More recently, other routes, such as Web-based trial registries and documents prepared for regulatory agencies, are being considered for dissemination. A linked study by Maund and colleagues 1 shows the value of a specific type of regulatory document, the clinical study report.…”

“…The authors of the linked study 1 analyzed the benefits and harms of duloxetine for the treatment of stress urinary incontinence on the basis of four clinical trials, using clinical study reports (including individual patient data) requested from the EMA. In addition to end points related to the drug's benefits and general harms, they conducted an in-depth analysis of rare psychiatric adverse events that they considered particularly important, namely, suicidality and violence-related harms and their potential precursors (e.g., activation, emotional disturbance, psychotic events).…”