Choosing the Most Efficacious and Safe Oral Treatment for Idiopathic Overactive Bladder: A Systematic Review and Network Meta-analysis.

CONTEXT: The choice of the most efficacious drug for patients with idiopathic overactive bladder (IOAB) remains challenging. OBJECTIVE: The aim of this network meta-analysis was to determine the most efficacious oral antimuscarinic or ß-adrenoceptor agonist accounting for adverse events for the management of IOAB. EVIDENCE ACQUISITION: A comprehensive electronic search was done in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Ovid for studies in any language in February 2021 considering the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. We included all randomized controlled trials assessing oral antimuscarinics or ß-adrenoceptor agonists for the treatment of IOAB. We determined the effect of specific bothersome symptoms separately. EVIDENCE SYNTHESIS: Fifty-four articles were included in our analysis. The most efficacious agents considering the evaluated outcomes were oxybutynin 15 mg/d in reducing incontinence episodes, imidafenacin 0.5 mg/d together with solifenacin 10 and 5 mg/d in reducing micturition episodes, fesoterodine 4 and 8 mg/d as well as solifenacin 10 mg/d in reducing urgency episodes, imidafenacin 0.5 mg/d and solifenacin 10 mg/d in reducing urgency urinary incontinence episodes, and solifenacin 10 mg/d, vibegron 50 mg/d, and fesoterodine 8 mg/d in improving the voided volume. Gastrointestinal problems, especially due to antimuscarinic agents, were the most prevalent adverse events. CONCLUSIONS: Taken together, there is only minimal difference between the efficacy of oral antimuscarinics and that of ß-adrenoceptor agonists. Although finding the best medication for all is impossible, finding the best treatment for every individual patient can be done by considering the efficacy of a medicine for the most bothersome symptom(s) in balance with drug-specific adverse events. PATIENT SUMMARY: This study aimed to find the most efficient oral medication to treat overactive bladder, taking into consideration the adverse events. Based on our study, there is a minimal difference in the efficacy between the two major drug classes used to treat overactive bladder. Gastrointestinal problems were the most common adverse events in medical treatment of overactive bladder. Selection of the best treatment is possible through shared decision-making between the doctor and the patient based on the patient's most bothersome symptom. We provide a framework for physicians to facilitate shared decision-making with each individual patient.

The placebo and nocebo effects in functional urology.

A placebo is an inert substance normally used in clinical trials for comparison with an active substance. However, a placebo has been shown to have an effect on its own; commonly known as the placebo effect. A placebo is an essential component in the design of conclusive clinical trials but has itself become the focus of intense research. The placebo effect is partly the result of positive expectations of the recipient on the state of health. Conversely, a nocebo effect is when negative expectations from a substance lead to poor treatment outcomes and/or adverse events. Randomized controlled trials in functional urology have demonstrated the importance of the placebo and nocebo effects across different diseases such as overactive bladder, urinary incontinence, lower urinary tract symptoms and interstitial cystitis/painful bladder syndrome, as well as male and female sexual dysfunction. Understanding the true nature of the placebo-nocebo complex and the scope of its effect in functional urology could help urologists to maximize the positive effects of this phenomenon while minimizing its potentially negative effects.

Medical practice and placebo response: an inseparable bond?

The history of medicine and the history of placebo are closely intertwined. To understand placebo and its effects this article gives a brief overview about its history, the possible mechanisms of action and its counterpart, nocebo.The Catholic Church used placebo around the sixteenth century for the separation from real and incorrect exorcisms, but it needed Henry Beecher during World War II to quantify the placebo effect as control arm in well-designed studies.Until today the different mechanisms of action of placebo remain poorly researched. Understanding them would allow its effect to be modulated to better serve in research and clinical settings. Expectation, psychosocial context and conditioning play a significant role in the effect size and amplitude.The counterpart, nocebo, is even less investigated, even it is commonly observed as adverse effects during medical treatments.Conclusion: Placebo and nocebo are both underestimated and underresearched in their value. Through further investigation doctors could strengthen the placebo response and prevent adverse effects to help their patients at low cost. These techniques would benefit the patient-doctor relationship, which is the alter of a trust-based successful therapy.