Department of Clinical Pharmacology, University Hospital Bispebjerg and Frederiksberg, Copenhagen, Denmark.
Department of Gynecology and Obstetrics, Herlev and Gentofte Hospital, Herlev, Denmark.
Neurourol Urodyn. 2019 Apr;38(4):1076-1080. doi: 10.1002/nau.23955. Epub 2019 Mar 7.
In two open-label trials, imipramine alleviated symptoms in patients with stress urinary incontinence and is therefore used off-label for this indication. However, it has never been confirmed that imipramine increases urethral pressure in a placebo-controlled setting. The purpose of this study was to investigate whether imipramine increases the opening urethral pressure compared to placebo in healthy women using urethral pressure reflectometry.
A randomized, double-blind, placebo-controlled, crossover study in 16 healthy women. Opening urethral pressure was measured predose and 1 hour after a single dose of 50 mg imipramine or placebo. The washout period was minimum of 1 week. The study was approved by the local ethics committee, conducted according to the Good Clinical Practice guidelines, and registered on ClinicalTrials.gov and EudraCT before recruitment of subjects. Funding was provided by the clinical department.
There were no dropouts and no serious adverse events. There were 13 adverse drug reactions related to imipramine in seven subjects, one adverse event related to placebo, and two adverse events related to the measurements with urethral pressure reflectometry. Imipramine compared to placebo increased opening urethral pressure in the resting condition with 6.5 cmH O (95% confidence interval [CI]: -0.5, 13.5), P = 0.07, and in the squeeze condition with 7.9 cmH O (95% CI: -0.3, 16.1), P = 0.06.
In conclusion, the increase in opening urethral pressure after imipramine treatment compared to placebo was neither statistically significant nor clinically relevant, and we do therefore not recommend the off-label use of imipramine for the treatment of stress urinary incontinence.
在两项开放标签试验中，丙咪嗪可缓解压力性尿失禁患者的症状，因此被超适应证用于该疾病。然而，丙咪嗪在安慰剂对照环境中增加尿道压力的作用从未得到证实。本研究旨在通过尿道压力反射测量法，调查健康女性单次服用 50mg 丙咪嗪或安慰剂后，与安慰剂相比，丙咪嗪是否能增加尿道开口压力。
本研究为 16 名健康女性参与的随机、双盲、安慰剂对照、交叉研究。在单次服用 50mg 丙咪嗪或安慰剂前及服药 1 小时后，测量尿道开口压力。洗脱期至少为 1 周。该研究经当地伦理委员会批准，遵循良好临床实践指南进行，并在招募受试者前于 ClinicalTrials.gov 和 EudraCT 进行注册。研究资金由临床科室提供。
无脱落病例，也无严重不良事件。7 名受试者中共有 13 例与丙咪嗪相关的药物不良反应，1 例与安慰剂相关的不良事件，2 例与尿道压力反射测量相关的不良事件。与安慰剂相比，丙咪嗪增加了静息状态下的尿道开口压力，差值为 6.5cmH2O（95%置信区间[CI]：-0.5，13.5），P=0.07；增加了收缩状态下的尿道开口压力，差值为 7.9cmH2O（95%CI：-0.3，16.1），P=0.06。
综上所述，与安慰剂相比，丙咪嗪治疗后尿道开口压力的增加既无统计学意义，也无临床意义，因此我们不建议将丙咪嗪超适应证用于治疗压力性尿失禁。
