{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T03:24:38Z","timestamp":1740108278600,"version":"3.37.3"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2024,8,21]],"date-time":"2024-08-21T00:00:00Z","timestamp":1724198400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,8,21]],"date-time":"2024-08-21T00:00:00Z","timestamp":1724198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001734","name":"Copenhagen University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001734","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int Urogynecol J"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n              <jats:title>Introduction and Hypothesis<\/jats:title>\n              <jats:p>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.<\/jats:p>\n            <\/jats:sec><jats:sec>\n              <jats:title>Methods<\/jats:title>\n              <jats:p>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\u2019 washout. At each visit, they received a single dose of 50\u00a0mg 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.<\/jats:p>\n            <\/jats:sec><jats:sec>\n              <jats:title>Results<\/jats:title>\n              <jats:p>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 cmH<jats:sub>2<\/jats:sub>O (95% confidence interval [CI] 2.0\u201328.2 cmH<jats:sub>2<\/jats:sub>O, <jats:italic>p<\/jats:italic>\u2009=\u20090.03) in the resting state and 15.1 (95% CI 4.2\u201326.0 cmH<jats:sub>2<\/jats:sub>O, <jats:italic>p<\/jats:italic>\u2009=\u20090.01) cmH<jats:sub>2<\/jats:sub>O during squeezing.<\/jats:p>\n            <\/jats:sec><jats:sec>\n              <jats:title>Conclusions<\/jats:title>\n              <jats:p>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.<\/jats:p>\n            <\/jats:sec>","DOI":"10.1007\/s00192-024-05890-5","type":"journal-article","created":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T16:45:45Z","timestamp":1724345145000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of Single-Dose Imipramine on Anal Sphincter Tone in Healthy Women: A Randomized, Placebo-Controlled Study Using Anal Acoustic Reflectometry"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5713-2707","authenticated-orcid":false,"given":"Thea","family":"Christoffersen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonatan","family":"Kornholt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Troels","family":"Riis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David P.","family":"Sonne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niels","family":"Klarskov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,8,21]]},"reference":[{"issue":"3","key":"5890_CR1","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s00192-012-1889-6","volume":"24","author":"TM Smith","year":"2013","unstructured":"Smith TM, Menees SB, Xu X, Saad RJ, Chey WD, Fenner DE. Factors associated with quality of life among women with fecal incontinence. Int Urogynecol J. 2013;24(3):493\u20139.","journal-title":"Int Urogynecol J"},{"issue":"6","key":"5890_CR2","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1016\/j.ajog.2005.07.018","volume":"193","author":"JL Melville","year":"2005","unstructured":"Melville JL, Fan MY, Newton K, Fenner D. Fecal incontinence in US women: a population-based study. Am J Obstet Gynecol. 2005;193(6):2071\u20136.","journal-title":"Am J Obstet Gynecol"},{"issue":"3","key":"5890_CR3","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1002\/ueg2.12213","volume":"10","author":"SL Assmann","year":"2022","unstructured":"Assmann SL, Keszthelyi D, Kleijnen J, Anastasiou F, Bradshaw E, Brannigan AE, et al. Guideline for the diagnosis and treatment of Faecal Incontinence\u2014A UEG\/ESCP\/ESNM\/ESPCG collaboration. United European Gastroenterol J. 2022;10(3):251\u201386.","journal-title":"United European Gastroenterol J"},{"issue":"1","key":"5890_CR4","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.gtc.2021.10.005","volume":"51","author":"S Menees","year":"2022","unstructured":"Menees S, Chey WD. Fecal incontinence. Gastroenterol Clin North Am. 2022;51(1):71\u201391.","journal-title":"Gastroenterol Clin North Am"},{"issue":"5","key":"5890_CR5","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1007\/s10350-006-0778-9","volume":"50","author":"EDMD Ehrenpreis","year":"2007","unstructured":"Ehrenpreis EDMD, Chang DBA, Eichenwald EBS. Pharmacotherapy for fecal incontinence: a review. Dis Colon Rectum. 2007;50(5):641\u20139.","journal-title":"Dis Colon Rectum"},{"issue":"12","key":"5890_CR6","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1007\/BF02236848","volume":"43","author":"GA Santoro","year":"2000","unstructured":"Santoro GA, Eitan BZ, Pryde A, Bartolo DC. Open study of low-dose amitriptyline in the treatment of patients with idiopathic fecal incontinence. Dis Colon Rectum. 2000;43(12):1676\u201381.","journal-title":"Dis Colon Rectum"},{"issue":"2","key":"5890_CR7","doi-asserted-by":"crossref","first-page":"R416","DOI":"10.1152\/ajpregu.00111.2010","volume":"299","author":"KB Thor","year":"2010","unstructured":"Thor KB, de Groat WC. Neural control of the female urethral and anal rhabdosphincters and pelvic floor muscles. Am J Physiol Regul Integr Comp Physiol. 2010;299(2):R416\u201338.","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"issue":"4","key":"5890_CR8","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1136\/gut.2004.047696","volume":"54","author":"AE Bharucha","year":"2005","unstructured":"Bharucha AE. Relationship between symptoms and disordered continence mechanisms in women with idiopathic faecal incontinence. Gut. 2005;54(4):546\u201355.","journal-title":"Gut"},{"issue":"2","key":"5890_CR9","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1111\/j.1464-410X.2007.06922.x","volume":"100","author":"N Klarskov","year":"2007","unstructured":"Klarskov N, Lose G. Urethral pressure reflectometry vs urethral pressure profilometry in women: a comparative study of reproducibility and accuracy. BJU Int. 2007;100(2):351\u20136.","journal-title":"BJU Int"},{"issue":"8","key":"5890_CR10","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1002\/nau.20617","volume":"27","author":"N Klarskov","year":"2008","unstructured":"Klarskov N, Lose G. Urethral pressure reflectometry and pressure profilometry in healthy volunteers and stress urinary incontinent women. Neurourol Urodyn. 2008;27(8):807\u201312.","journal-title":"Neurourol Urodyn"},{"issue":"9","key":"5890_CR11","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1097\/DCR.0b013e318223fbcb","volume":"54","author":"PJ Mitchell","year":"2011","unstructured":"Mitchell PJ, Klarskov N, Telford KJ, Hosker GL, Lose G, Kiff ES. Anal acoustic reflectometry: a new reproducible technique providing physiological assessment of anal sphincter function. Dis Colon Rectum. 2011;54(9):1122\u20138.","journal-title":"Dis Colon Rectum"},{"issue":"2","key":"5890_CR12","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1097\/DCR.0b013e31823b2499","volume":"55","author":"PJ Mitchell","year":"2012","unstructured":"Mitchell PJ, Klarskov N, Telford KJ, Hosker GL, Lose G, Kiff ES. Viscoelastic assessment of anal canal function using acoustic reflectometry: a clinically useful technique. Dis Colon Rectum. 2012;55(2):211\u20137.","journal-title":"Dis Colon Rectum"},{"issue":"12","key":"5890_CR13","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1002\/bjs.8943","volume":"99","author":"BR Hornung","year":"2012","unstructured":"Hornung BR, Mitchell PJ, Carlson GL, Klarskov N, Lose G, Kiff ES. Comparative study of anal acoustic reflectometry and anal manometry in the assessment of faecal incontinence. Br J Surg. 2012;99(12):1718\u201324.","journal-title":"Br J Surg"},{"issue":"5","key":"5890_CR14","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1097\/DCR.0000000000000790","volume":"60","author":"BR Hornung","year":"2017","unstructured":"Hornung BR, Telford KJ, Carlson GL, Mitchell PJ, Klarskov N, Kiff ES. Use of anal acoustic reflectometry in the evaluation of men with passive fecal leakage. Dis Colon Rectum. 2017;60(5):521\u20136.","journal-title":"Dis Colon Rectum"},{"issue":"4","key":"5890_CR15","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1002\/nau.23955","volume":"38","author":"J Kornholt","year":"2019","unstructured":"Kornholt J, Sonne DP, Riis T, Sonne J, Klarskov N. Effect of imipramine on urethral opening pressure: a randomized, double-blind, placebo-controlled crossover study in healthy women. Neurourol Urodyn. 2019;38(4):1076\u201380.","journal-title":"Neurourol Urodyn"},{"issue":"4","key":"5890_CR16","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1007\/s00192-014-2512-9","volume":"26","author":"MA Malallah","year":"2015","unstructured":"Malallah MA, Al-Shaiji TF. Pharmacological treatment of pure stress urinary incontinence: a narrative review. Int Urogynecol J. 2015;26(4):477\u201385.","journal-title":"Int Urogynecol J"},{"issue":"7","key":"5890_CR17","doi-asserted-by":"crossref","first-page":"e14496","DOI":"10.1111\/nmo.14496","volume":"35","author":"A O\u2019Connor","year":"2023","unstructured":"O\u2019Connor A, Byrne CM, Vasant DH, Sharma A, Liao D, Klarskov N, et al. Current and future perspectives on the utility of provocative tests of anal sphincter function: a state-of-the-art summary. Neurogastroenterol Motil. 2023;35(7):e14496.","journal-title":"Neurogastroenterol Motil"},{"issue":"7","key":"5890_CR18","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1111\/j.1463-1318.2010.02194.x","volume":"12","author":"PJ Mitchell","year":"2010","unstructured":"Mitchell PJ, Klarskov N, Hosker G, Lose G, Kiff ES. Anal acoustic reflectometry: a new technique for assessing anal sphincter function. Colorectal Dis. 2010;12(7):692\u20137.","journal-title":"Colorectal Dis"},{"issue":"1","key":"5890_CR19","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1002\/nau.24235","volume":"39","author":"NA Heywood","year":"2020","unstructured":"Heywood NA, Nicholson JE, Sharma A, Kiff ES, Klarskov N, Telford KJ. Continuous vs stepwise anal acoustic reflectometry: an improved technique for physiological measurement of anal sphincter function? Neurourol Urodyn. 2020;39(1):447\u201354.","journal-title":"Neurourol Urodyn"},{"key":"5890_CR20","doi-asserted-by":"crossref","unstructured":"Senn S. Cross-over trials in clinical research. 1st ed. Chichester\/New York: Wiley; 2002. Available from: http:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/0470854596","DOI":"10.1002\/0470854596"},{"key":"5890_CR21","doi-asserted-by":"crossref","DOI":"10.1201\/b17537","volume-title":"Design and analysis of cross-over trials","author":"B Jones","year":"2014","unstructured":"Jones B, Kenward MG. Design and analysis of cross-over trials. Boca Raton: CRC Press\/Taylor & Francis; 2014."},{"issue":"6","key":"5890_CR22","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/sj.bjp.0707253","volume":"151","author":"PK Gillman","year":"2007","unstructured":"Gillman PK. Tricyclic antidepressant pharmacology and therapeutic drug interactions updated: TCAs: pharmacology and interactions. Br J Pharmacol. 2007;151(6):737\u201348.","journal-title":"Br J Pharmacol"},{"issue":"8","key":"5890_CR23","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1212\/01.WNL.0000058749.49264.BD","volume":"60","author":"SH Sindrup","year":"2003","unstructured":"Sindrup SH, Bach FW, Madsen C, Gram LF, Jensen TS. Venlafaxine versus imipramine in painful polyneuropathy: a randomized, controlled trial. Neurology. 2003;60(8):1284\u20139.","journal-title":"Neurology"},{"issue":"7","key":"5890_CR24","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1111\/jgs.18372","volume":"71","author":"2023 American Geriatrics Society Beers Criteria\u00ae Update Expert Panel","year":"2023","unstructured":"2023 American Geriatrics Society Beers Criteria\u00ae Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria\u00ae for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2023;71(7):2052\u201381.","journal-title":"J Am Geriatr Soc"},{"issue":"3","key":"5890_CR25","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1097\/JCP.0b013e3181a5233f","volume":"29","author":"A Serretti","year":"2009","unstructured":"Serretti A, Chiesa A. Treatment-emergent sexual dysfunction related to antidepressants: a meta-analysis. J Clin Psychopharmacol. 2009;29(3):259\u201366.","journal-title":"J Clin Psychopharmacol"},{"issue":"2","key":"5890_CR26","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1097\/00004714-200204000-00008","volume":"22","author":"M Mavissakalian","year":"2002","unstructured":"Mavissakalian M, Perel J, Guo S. Specific side effects of long-term imipramine management of panic disorder. J Clin Psychopharmacol. 2002;22(2):155\u201361. https:\/\/doi.org\/10.1097\/00004714-200204000-00008","journal-title":"J Clin Psychopharmacol"},{"issue":"2","key":"5890_CR27","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1111\/j.1365-2036.1994.tb00273.x","volume":"8","author":"DA Gorard","year":"1994","unstructured":"Gorard DA, Libby GW, Farthing MJG. Influence of antidepressants on whole gut and orocaecal transit times in health and irritable bowel syndrome. Aliment Pharmacol Ther. 1994;8(2):159\u201366.","journal-title":"Aliment Pharmacol Ther"},{"issue":"1","key":"5890_CR28","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1007\/BF02063948","volume":"40","author":"DA Gorard","year":"1995","unstructured":"Gorard DA, Libby GW, Farthing MJG. Effect of a tricyclic antidepressant on small intestinal motility in health and diarrhea-predominant irritable bowel syndrome. Digest Dis Sci. 1995;40(1):86\u201395.","journal-title":"Digest Dis Sci"},{"issue":"10414","key":"5890_CR29","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1016\/S0140-6736(23)01523-4","volume":"402","author":"AC Ford","year":"2023","unstructured":"Ford AC, Wright-Hughes A, Alderson SL, Ow PL, Ridd MJ, Foy R, et al. Amitriptyline at low-dose and titrated for irritable bowel syndrome as second-line treatment in primary care (ATLANTIS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023;402(10414):1773\u201385.","journal-title":"Lancet"},{"issue":"1","key":"5890_CR30","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1002\/nau.23282","volume":"37","author":"N Klarskov","year":"2018","unstructured":"Klarskov N, Cerneus D, Sawyer W, Newgreen D, Van Till O, Lose G. The effect of single oral doses of duloxetine, reboxetine, and midodrine on the urethral pressure in healthy female subjects, using urethral pressure reflectometry. Neurourol Urodyn. 2018;37(1):244\u20139.","journal-title":"Neurourol Urodyn"}],"container-title":["International Urogynecology Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00192-024-05890-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00192-024-05890-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00192-024-05890-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T16:54:43Z","timestamp":1724345683000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00192-024-05890-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,21]]},"references-count":30,"alternative-id":["5890"],"URL":"https:\/\/doi.org\/10.1007\/s00192-024-05890-5","relation":{},"ISSN":["0937-3462","1433-3023"],"issn-type":[{"type":"print","value":"0937-3462"},{"type":"electronic","value":"1433-3023"}],"subject":[],"published":{"date-parts":[[2024,8,21]]},"assertion":[{"value":"14 March 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 July 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 August 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Ethical approval was obtained from the Regional Research Ethics Committee of the Capital Region of Denmark (approval no. H\u201017007330).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Statement"}},{"value":"None.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of Interest"}}]}}