Affiliation:
1. Department of Clinical Pharmacology Copenhagen University Hospital – Bispebjerg and Frederiksberg Copenhagen Denmark
2. Department of Clinical Medicine University of Copenhagen Copenhagen Denmark
3. Department of Gynecology and Obstetrics Copenhagen University Hospital – Herlev and Gentofte Herlev Denmark
Abstract
AbstractBackgroundIn placebo‐controlled clinical trials, reboxetine, a selective noradrenaline reuptake inhibitor, increases urethral pressure and relieves stress urinary incontinence symptoms in women. Considering the close connection in neural regulation of the external urethral and anal sphincters, we hypothesized that reboxetine may also enhance anal sphincter pressure. Conversely, it is believed that selective serotonin reuptake inhibitors may contribute to fecal incontinence by reducing anal sphincter pressure. In this study, we investigated the effect of reboxetine and citalopram on anal opening pressure in healthy female volunteers.MethodsIn a double‐blind, three‐way crossover trial, 24 female participants received single doses of 40 mg citalopram, 8 mg reboxetine, and matching placebos, with a minimum of 8‐day washout between sessions. Using anal acoustic reflectometry, we measured anal opening pressure during both resting and squeezing conditions at the estimated time of peak plasma concentration for both study drugs.Key ResultsCompared with placebo, reboxetine increased anal opening pressure with 23.4 cmH2O (95% confidence interval [CI] 16.5–30.2, p < 0.001) during rest and with 22.5 cmH2O (95% CI 15.2–29.8, p < 0.001) during squeeze. Citalopram did not change anal opening pressure statistically significantly compared to placebo.Conclusions & InferencesAn 8‐mg dose of reboxetine increased anal opening pressure substantially in healthy women, suggesting potential benefits for fecal incontinence symptoms. In contrast, a 40‐mg dose of citalopram showed a marginal and statistically insignificant effect on anal opening pressure, indicating that selective serotonin reuptake inhibitors do not contribute to fecal incontinence by reducing anal sphincter tone.