Department of Clinical Pharmacology, Copenhagen University Hospital-Bispebjerg and Frederiksberg, Bispebjerg Bakke 23, 2nd Floor, 2400, Copenhagen, Denmark.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Int Urogynecol J. 2024 Sep;35(9):1873-1879. doi: 10.1007/s00192-024-05890-5. Epub 2024 Aug 21.
Despite the high prevalence of fecal incontinence, existing treatment options may be inadequate. Drugs that enhance the tone of the anal sphincter complex could potentially be an effective pharmacological approach. This study investigated the effect of the tricyclic antidepressant imipramine on anal sphincter tone in healthy women, employing anal acoustic reflectometry as the evaluating method.
In a double-blind, randomized, placebo-controlled crossover study, 16 healthy female volunteers were randomized to one of two treatment sequences. The participants attended two study visits separated by at least 7 days' washout. At each visit, they received a single dose of 50 mg imipramine or matching placebo, in alternating order. We assessed the anal opening pressure under the resting state and during voluntary squeezing of the pelvic floor. Measurements were performed pre-dose and 1 h after drug administration, corresponding to the estimated time of peak plasma concentration of imipramine.
All participants completed the study. In total, 44% of the participants reported at least one adverse effect, primarily anticholinergic. Compared with placebo, imipramine increased anal opening pressure by 15.2 cmHO (95% confidence interval [CI] 2.0-28.2 cmHO, p = 0.03) in the resting state and 15.1 (95% CI 4.2-26.0 cmHO, p = 0.01) cmHO during squeezing.
The findings indicate that imipramine increases anal sphincter tone in healthy women. However, further research is required to evaluate its clinical impact on individuals with fecal incontinence. This research also demonstrates the effectiveness of using anal acoustic reflectometry for assessing pharmacological effects on anal sphincter function.
尽管粪便失禁的患病率很高，但现有的治疗选择可能并不充分。增强肛门括约肌复合体张力的药物可能是一种有效的药物治疗方法。本研究采用肛门声学反射测量法，研究了三环类抗抑郁药丙咪嗪对健康女性肛门括约肌张力的影响。
在一项双盲、随机、安慰剂对照交叉研究中，16 名健康女性志愿者随机分为两组。参与者在至少 7 天的洗脱期后参加了两次研究访问。每次访问时，他们分别接受单次剂量 50mg 丙咪嗪或匹配的安慰剂，以交替顺序给药。我们评估了静息状态和自主收缩盆底时的肛门开口压力。在给药前和给药后 1 小时进行测量，这对应于丙咪嗪估计的血浆峰值浓度时间。
所有参与者均完成了研究。共有 44%的参与者报告了至少一种不良反应，主要为抗胆碱能作用。与安慰剂相比，丙咪嗪在静息状态下增加了 15.2cmH2O（95%置信区间[CI] 2.0-28.2cmH2O，p=0.03），在收缩状态下增加了 15.1cmH2O（95%CI 4.2-26.0cmH2O，p=0.01）。
研究结果表明，丙咪嗪可增加健康女性的肛门括约肌张力。然而，需要进一步研究来评估其对粪便失禁患者的临床影响。该研究还证明了使用肛门声学反射测量法评估药物对肛门括约肌功能影响的有效性。
