Department of Clinical Pharmacology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Neurogastroenterol Motil. 2024 Oct;36(10):e14882. doi: 10.1111/nmo.14882. Epub 2024 Jul 30.
In 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.
In 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.
Compared with placebo, reboxetine increased anal opening pressure with 23.4 cmHO (95% confidence interval [CI] 16.5-30.2, p < 0.001) during rest and with 22.5 cmHO (95% CI 15.2-29.8, p < 0.001) during squeeze. Citalopram did not change anal opening pressure statistically significantly compared to placebo.
CONCLUSIONS & INFERENCES: An 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.
在安慰剂对照临床试验中，选择性去甲肾上腺素再摄取抑制剂瑞波西汀可增加尿道压力并缓解女性压力性尿失禁症状。考虑到尿道外括约肌和肛门括约肌在神经调节方面的密切联系，我们假设瑞波西汀也可能增强肛门括约肌压力。相反，选择性 5-羟色胺再摄取抑制剂通过降低肛门括约肌压力可能导致粪便失禁。在这项研究中，我们调查了瑞波西汀和西酞普兰对健康女性志愿者肛门开口压力的影响。
在一项双盲、三向交叉试验中，24 名女性参与者接受了 40mg 西酞普兰、8mg 瑞波西汀和匹配安慰剂的单次剂量，每次给药之间至少有 8 天的洗脱期。使用肛门声学反射测量法，我们在两种研究药物估计达到血浆峰值浓度的时间测量了休息和挤压状态下的肛门开口压力。
与安慰剂相比，瑞波西汀在休息时使肛门开口压力增加了 23.4cmHO（95%置信区间[CI]为 16.5-30.2，p<0.001），在挤压时增加了 22.5cmHO（95%CI 为 15.2-29.8，p<0.001）。与安慰剂相比，西酞普兰的肛门开口压力没有统计学上的显著变化。
8mg 剂量的瑞波西汀可显著增加健康女性的肛门开口压力，提示对粪便失禁症状有潜在益处。相比之下，40mg 剂量的西酞普兰对肛门开口压力的影响微乎其微，统计学上无显著意义，表明选择性 5-羟色胺再摄取抑制剂不会通过降低肛门括约肌张力导致粪便失禁。
