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Effect of dose escalation on the tolerability and efficacy of duloxetine in the treatment of women with stress urinary incontinence

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Abstract

To assess the impact of duloxetine dose escalation on tolerability and efficacy, 516 women with stress urinary incontinence were randomized to receive placebo or duloxetine in one of three regimens: 40 mg BID for 8 weeks, 40 mg QD for 2 weeks escalating to 40 mg BID for 6 weeks or 20 mg BID for 2 weeks escalating to 40 mg BID for 6 weeks. A non-inferiority analysis confirmed that the 20 mg BID starting dose was significantly better than the other two duloxetine regimens for nausea reduction (16.5% vs 25.2% and 29.4%). There were also significant differences in the discontinuation rates (7.5% vs 11.8% and 16.2%). The efficacy after 4 weeks was significantly better with duloxetine than with placebo. Starting duloxetine at 20 mg BID for 2 weeks before increasing to 40 mg BID significantly improved tolerability but did not impact duloxetine efficacy after all the subjects had been on 40 mg BID for at least 2 weeks.

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Acknowledgements

The principal investigators in the Duloxetine Dose Escalation Study Group included the following: in Brazil: Márcia Salvador Geo, Hospital Mater Dei, Diretoria, Belo Horizonte; Eric Roger Wroclawski, Faculdade de Medicina da Fundacão do ABC, Santo André; Geraldo Eduardo Pinheiro, Hospital São Carlos, Fortaleza; Homero Bruschini, Hospital São Paulo, São Paulo; Irineu Rubinstein, Hospital Universitário Gaffreé e Guinle da UNIRIO, Rio de Janeiro; João Luiz Amaro, Hospital das Clínicas da FM-UNESP, Botucatu; Luis Seabra Rios, Hospital do Servidor Publico Estadual, São Paulo; Marcio Josbete Prado, Private Practice Office, Salvador; Paulo Rodrigues Palma, Hospital das Clínicas da UNICAMP, Campinas; Ronaldo Damião, Hospital Universitário Pedro Ernesto-UERJ, Rio de Janeiro; Aparecida Maria Pacetta, Faculdade de Medicina da (UNISA), São Paulo; Anuar Ibrahim Mitre, Hospital das Clínicas de FMUSP, São Paulo. In Canada: Céline Bouchard, Clinique de Recherche en Santé de la Femme Inc., Québec; Jacques Corcos, McGill Urology Associates, Montréal; Érik Schick, Maisonneuve-Rosemont Hospital, Montréal; Le Mai Tu, CHUS-Hopital Fleurimont, Sherbrooke; Luc Valiquette, CHUM-Hopital St Luc, Montréal; Jean-Guy Vézina, Centre de recherche clinique en urologie, Québec. In France: Gerard Amarenco, Hôpital Rothschild, Paris; Béatrice Cuzin, Hospital Edouard Herriot, Lyon; Francois Haab, Hôpital Tenon, Paris; Ariane Cortesse-Lacaine, Hôpital Saint Louis, Paris; Philippe Grise, Service d’Urologie, Rouen; Bernard Jacquetin, Hopital Hôtel Dieu, Cedex; Pierre Costa, Hôpital Caremeau, Nimes; Oliver Lan, Centre Synergia, Carpentras; Christian Jouffroy, Cabinet Medical, Metz; Gerard Amerenco, Hopital Rothschild, Paris; Shephane Droupy, Centre Hospitalier Universitaire de Bicetre, Le Kremlin Bicetre. In Germany: Christian Hampel, Johannes-Gutenberg-University Mainz, Mainz; Jörg Willgerodt, Urologische Praxis, Leipzig; Guenther Egghart, Kreiskrankenhaus Sigmaringen, Sigmaringen; Annette Herzner, Klinische Forschung Hamburg, Hamburg; Heike Wilken, Fachaerztin fuer Gynaekologie und Geburtshilfe, Rostock; Wolfgang Warnack, Urological practice, Hagenow; Dirk Watermann, Universitaetsfrauenklinik der Albert-Ludwigs University, Freiburg; Christian Goepel, Martin-Luther Universität Halle-Wittenberg, Halle; Katharina Jundt, Klinikum der Universitaet München, München; Olaf Dilk, Universitätskliniken Des Saarlandes, Homburg. In Italy: Roberto Carone, Hospital Colle Della Maddalena, Turin; Mauro Cervigni, Ospedale San Carlo Di Nancy, Rome; Francesco Pesce, University of Verona, Verona; Rodolfo Milani, University of Milan, Milan; Massimo Porena, University of Perugia, Perugia. In Mexico: Sergio Ureta Sánchez, Hospital Espanol, Mexico City; Patricia Velásquez Castellanos, Hospital Civil de Guadalajara, Guadalajara; Eduardo Neri Ruz, Clínica de Especialidades de la Mujer del Hospital Militar, Mexico City; José Pérez Ortega, Centro de Continencia y Urología Integral, Mexico City; Sebastián Zepeda Contreras, Hospital Universitario de Saltillo, Saltillo; José Campos Contreras, Hospital Central Militar, Mexico City. In Puerto Rico: Henry Rodriguez Ginorio, Torre Hospital Auxilio Mutuo, San Juan; Jorge Rivera Herrara, San Jorge Medical Office Bldg., San Juan; Richard Baez, Centro Urologico del Caribe, Ponce; Héctor Cardona, Sociedadn Urológica Especializada, Santurce; Lourdes Guerrios, RCMI Clinical Research Group, San Juan; Marie Zweig, Centro Ginecológico, Santa Rita. In Spain: David Castro-Díaz, Hospital Universitario de Canarias, Santa Cruz de Tenerife; Juan Martínez Escoriza, Hospital General de Alicante, Alicante; Fernando Jiménez Cruz, University Hospital La Fe, Valencia; Manuel Fillol Crespo, Hospital La Plana, Castellón; Fernando González-Chamorro, Fundación Alcorcón, Madrid; Montserrat Espuña Pons, Hospital Clinic I Provincial, Barcelona; Jesus Romero Maroto, Hospital Universitario San Juan de Alicante, Alicante; Remidio Vela Navarrete, Fundación Jiménez Díaz, Madrid; Miguel Puyol Pallás, Hospital Sant Joan de Deu (Martorell).

Funding

This study was sponsored and funded by Eli Lilly and Company and by Boehringer Ingelheim GmbH, who market duloxetine for the treatment of women with stress urinary incontinence.

Conflict of interest statement

Commercial or other associations that might pose a conflict of interest: Drs. Voss, Yalcin and Bump are full-time employees of Lilly Research Laboratories and Eli Lilly and Company.

All other authors were principal investigators for their respective study site during this trial. Additional commercial associations for the authors are as follows: David Castro-Diaz, Advisory board member for Eli Lilly and Company and Boehringer Ingelheim; Advisory board member for Astellas Pharma; Paulo C.R. Palma, no additional disclosures; Céline Bouchard, no additional disclosures; Francois Haab, Advisor for Astellas Pharma, Novartis, UCB, Glaxo Smith Kline, Gynecare, and Boston Scientific; Christian Hampel, Advisory Board member and/or lecturer for Eli Lilly and Company and Boehringer Ingelheim, UCB, Medac, Bayer Health Care, Allergan, Pfizer, and Medtronic; Roberto Carone, no additional disclosures; Sebastian Zepeda Contreras, no additional disclosures; Henry Rodriguez Ginorio, Member of Eli Lilly and Company speaker bureau.

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Correspondence to Richard C. Bump.

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Castro-Diaz, D., Palma, P.C.R., Bouchard, C. et al. Effect of dose escalation on the tolerability and efficacy of duloxetine in the treatment of women with stress urinary incontinence. Int Urogynecol J 18, 919–929 (2007). https://doi.org/10.1007/s00192-006-0256-x

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