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

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.

Internet‐based treatment of stress urinary incontinence: a randomised controlled study with focus on pelvic floor muscle training

“…In an Australian study, 83 women with a mean age of 71.8 years and a baseline ICIQ-UI SF score of 10.4 improved their score by 3.0 after 3 months of pelvic floor muscle training, or by 1.3 after bladder training 36. In a study on duloxetine treatment, the active treatment arm obtained a 2.8 point improvement in the ICIQ-UI SF and the placebo arm improved by 1.7 points 37.…”

Observational study on safety and tolerability of duloxetine in the treatment of female stress urinary incontinence in German routine practice

“…There are additional differences between the present observational and most previously reported randomized duloxetine studies in SUI patients. Firstly, except for one phase IV study of SUI published after initiation of the present study, all randomized duloxetine studies had not involved any dose‐escalation but had started all patients on the target dose. In line with the observational character of our study, we had not specified duloxetine doses to be used.…”

New Options and Strategies for the Treatment of Urinary Incontinence

“…The discontinuation rates for the 20-mg twice daily initial dosage and the placebo arms were not statistically different from one another. 63 More serious adverse effects were rare and not statistically different from placebo. [58][59][60]62 Dosing alterations are not recommended for elderly subjects; however, use is not recommended when the creatinine clearance is below 30 mL/min or when there is hepatic impairment.…”

“…58 The dosagetitration study by Castro-Diaz and colleagues demonstrated that starting duloxetine at 20 mg twice daily for 2 weeks before titration, rather than initiating 40 mg daily or 40 mg twice daily, may be superior with respect to reducing treatment-related adverse events and subsequent study withdrawals without significantly affecting efficacy. 63 The discontinuation rates were 7.5% for the study arm with an initial dosage of 20 mg twice daily, 11.8% for the 40-mg daily initial dosage, 16.2% for the 40-mg twice daily initial dosage, and 5.8% for the placebo arm. The discontinuation rates for the 20-mg twice daily initial dosage and the placebo arms were not statistically different from one another.…”