Tolerability and Efficacy of Duloxetine in a Nontrial Situation

Abstract

Duloxetine, a potent serotonin and noradrenaline reuptake inhibitor, is the first drug licensed in England for use in treating stress urinary incontinence (USI). Data from double-blind placebo-controlled trials show that it is significantly more effective than placebo in lowering the frequency of incontinent episodes, but very little is known about duloxetine outside of trials sponsored by the manufacturer. This prospective observational study evaluated duloxetine in 222 women diagnosed as having either USI or mixed USI and detrusor overactivity (DOA). The results of treatment over 4 months were evaluated using the Patient Global Impression of Improvement (PGI-I) questionnaire. Two-thirds of the women received 40 mg of duloxetine twice daily from the outset, and nearly all of the rest received escalating doses up to a maximum of 40 mg twice daily. Three women received 20 mg twice daily throughout. Two thirds of women discontinued treatment because of either lack of effectiveness or adverse side effects. Withdrawal because of adverse effects was significantly more frequent in women whose initial dose was 40 mg twice daily than in those taking escalating doses. None of the side effects were considered to be serious. Safety profiles were similar for women having USI only and those with combined USI and DOA. Nine women, 7 of whom had mixed incontinence, reported that their incontinence had become worse. Four women expressed a preference for surgery rather than long-term medication despite improvement in their PGI-I scores. Considering women who did not tolerate duloxetine, the overall rate of improvement was 37%. The investigators conclude that, in a nontrial setting, women with USI or mixed USI/DOA do not tolerate duloxetine well, although an escalating dose regimen may be better received. Women with isolated USI and those with combined USI and DOA are equally likely to improve when treated with duloxetine.