• Hadi Mostafaei, Keiichiro Mori, Fahad Quhal, Noriyoshi Miura, Reza Sari Motlagh, Benjamin Pradere, Ekaterina Laukhtina, Ivan Lysenko, Sajjad Ghaffari, Sakineh Hajebrahimi, and Shahrokh F Shariat.
• Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. Electronic address: hadimosta@gmail.com.
• Eur Urol Focus. 2020 Nov 2.

ContextThe role of a nocebo response in managing urology patients is unclear.ObjectiveTo assess the nocebo response in randomized placebo-controlled overactive bladder (OAB) trials of pharmacological treatment by investigating the adverse events in the placebo arms.Evidence AcquisitionPubMed, Scopus, Embase, and Cochrane Central Register of Controlled Trials were searched to identify potential randomized controlled trials published from 1998 to November 2019. After evaluating the risk of bias in the selected studies, all selected full-text articles were included due to their overall acceptable quality. We extracted the event rate of the most commonly reported adverse events in the placebo arms of OAB trials, and finally, we performed a meta-analysis to calculate the cumulative rate of certain adverse events. The primary outcomes were the event rate of adverse events in the placebo arms of OAB trials of pharmacological treatment, and differences in adverse events in the placebo groups based on drug type and routes of administration.Evidence SynthesisAfter a systematic search and risk of bias assessment, 57 trials comprising 15 446 patients were included in this systematic review. We selected 13 commonly reported adverse events for the meta-analysis. Owing to the possible differences in study samples and design, we used a random model for the analysis. The average age of the patients was 59.5 yr and 79.8% were female. Dry mouth was the most commonly evaluated adverse event reported in 57 studies comprising 15 324 patients; the mean event rate was 4.9% (95% confidence interval [CI] 0.042-0.057, p < 0.001). Constipation was the second most commonly reported adverse event in 49 studies comprising 14 556 patients; the mean event rate of constipation was 2.6% (95% CI 0.022-0.031, p < 0.001). The event rate of headache was evaluated in 33 studies comprising 10 202 patients, with a mean event rate of 3.1% (95% CI 0.026-0.037, p < 0.001).ConclusionsDry mouth, constipation, headache, and nasopharyngitis were the most prevalent events in the included studies. The nocebo response plays a statistically significant role in causing and/or facilitating adverse events. Health care providers should have a better understanding of the positive and negative expectations associated with therapies to achieve the best possible outcomes for each individual patient. Finally, identification of the real effect of nocebo requires studies that also include a no-treatment arm. Research could help us better understand and potentially modify the nocebo response.Patient SummaryIn this meta-analysis of 57 studies comprising 15 446 patients, we reviewed the adverse events extracted from the placebo arms of randomized controlled trials studying therapies for overactive bladder. Dry mouth, constipation, headache, and urinary tract infection were the most common adverse events. Adverse events varied based on the drug type and the route of administration. Negative expectations from the therapy and giving verbal information to the patient can cause/alleviate adverse events.Copyright © 2020. Published by Elsevier B.V.

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