Avoid common mistakes on your manuscript.
Chronic constipation is a symptom the physician faces almost daily. Treatment consists of several pharmacological and non-pharmacological options; the fact that to date, no treatment is completely effective justifies the numerous drugs available for this condition [1]. Moreover, there is a subset of constipated patients who have an unsatisfactory response to medical treatment or do not respond at all [1]. Until recently, these patients were often referred for surgical or other invasive approaches, with results that were far from optimal [2].
However, in recent years, new compounds have been developed for the treatment of chronic constipation, compounds that seem to have good efficacy with relatively few side effects [3]; one of these, prucalopride, has recently been released on the European market as an alternative treatment for female patients (representing more than 85 % of the overall population of constipated subjects) that show an insufficient response to laxatives [4].
To date, prucalopride has been mainly tested on patients recruited for clinical trials, and some authors claim that further subgroup analysis of the actual patient group of interest may be helpful in guiding clinical decision-making [5]. Thus, data on “real-life” patients or those with subtypes of constipation are still not available.
In this issue, Jadav and colleagues [6] try to give us some answers concerning the above points, by reporting in a retrospective study the treatment data of patients with constipation (defined according to the Rome III criteria) due to obstructed defecation (OD), to delayed transit (slow-transit constipation, STC), to a mixed-type (ODSTC), or to irritable bowel syndrome (IBS-C). These patients were given treatment according to the National Institute for Health and Clinical Excellence guidelines and had no relief from constipation despite trying at least two different types of laxatives and lifestyle modification for at least 6 months [7]. The authors compared the efficacy of prucalopride with the constipation subtypes according to simple criteria, most likely similar to those adopted in daily clinical practice: After 4 weeks, patients were asked whether they were satisfied with the treatment, and whether they wanted to continue with the treatment.
Overall, 42 % of the entire group benefitted from the treatment after 4 weeks, and after an average follow-up period of 5 months, the benefit persisted in 36 % of patients. These results (including dropouts) are comparable with results of larger published trials [8].
The interest of the study lies in the fact that the response to prucalopride was also observed in well-defined subgroups of constipated patients. There was a similar response between subgroups (59 % OD, 31 % STC, 43 % OD-STC, 44 % IBS-C), with surprisingly better results in OD patients. The surprise is due to the fact that previous studies suggested that the effect of the drug is lower on straining at stool [9], a symptom often considered as the hallmark of OD and mainly responding to biofeedback treatment [10]. However, OD itself is an umbrella term under which several pathophysiologic abnormalities may be found [11, 12], and it is likely that some patients with specific alterations may be more responsive to a pharmacological treatment. On the other hand, the patients with STC, in whom one would expect the best response, actually had the worst outcome. This fact, however, is not completely unexpected, since these are the patients who most frequently have features of intractable constipation, including a true colonic inertia [13], often due to important abnormalities of the enteric nervous system [14, 15]. These abnormalities led to the reclassification of many form of constipation (especially the more severe ones) as true enteric neuro-gliopathies [16, 17]. Interestingly, prucalopride worked well in IBS-C patients too, without an increased number of side effects such as abdominal pain (normally present in the symptoms cohort of these patients, and one of the most frequent side effects related to prucalopride).Thus, it is likely that the drug could also be effectively used in the subgroup of constipated patients, not fulfilling criteria for IBS, in whom pain is an important feature associated with constipation (painful constipation patients) [18].
In conclusion, the recent introduction of prucalopride for the treatment of constipated women (and, hopefully, also men in the near future), even though it cannot be considered as the “magic bullet,” since it does not work in all patients, has improved our chances to offer an effective treatment for this symptom, especially in those with scarce or no response to previous measures. Moreover, we must not forget that constipation is a complex, difficult symptom to treat, thereby often requiring complex therapeutic approaches [19]. Extensive knowledge of the available drugs and use of a multi-drug approach could eventually lead to better therapeutic success.
References
Bassotti G, Villanacci V (2013) A practical approach to diagnosis and management of functional constipation in adults. Intern Emerg Med. PMID:21964837
Sohn G, Yu CS, Kim CW et al (2011) Surgical outcomes after total colectomy with ileorectal anastomosis in patients with medically intractable slow transit constipation. J Korean Soc Coloproctol 27:180–187
Müller-Lissner S (2013) Pharmacokinetic and pharmacodynamic considerations for the current chronic constipation treatments. Expert Opin Drug Metab Toxicol 9:391–401
Tack J, Corsetti M (2012) Prucalopride: evaluation of the pharmacokinetics, pharmacodynamics, efficacy and safety in the treatment of chronic constipation. Expert Opin Drug Metab Toxicol 8:1327–1335
Pennant M, Orlando R, Barton P, Bayliss S, Routh K, Meads C (2011) Prucalopride for the treatment of women with chronic constipation in whom standard laxative regimens have failed to provide adequate relief. Health Technol Assess 15(Suppl 1):43–50
Jadav AM, Mcmullin CM, Smith J, Chapple K, Brown SR (2013) The association between prucalopride efficacy and constipation type. Tech Coloproctol. doi:10.1007/s10151-013-1017-8
National Institute for Health and Clinical Excellence. TA211 343 Constipation (women)-prucalopride: guidance. 15 Dec 2010
Camilleri M, Kerstens R, Rykx A, Vandeplassche L (2008) A placebo-controlled trial of prucalopride for severe chronic constipation. N Engl J Med 358:2344–2354
Tack J, Van Outyve M, Beyens G, Kerstens R, Vandeplassche L (2009) Prucalopride (Resolor) in the treatment of severe chronic constipation in patients dissatisfied with laxatives. Gut 58:357–365
Battaglia E, Serra AM, Buonafede G et al (2004) Long-term study on the effects of visual biofeedback and muscle training as a therapeutic modality in pelvic floor dyssynergia and slow-transit constipation. Dis Colon Rectum 47:90–95
D’Hoore A, Penninckx F (2003) Obstructed defecation. Colorectal Dis 5:280–287
Bove A, Pucciani F, Bellini M et al (2012) Consensus statement AIGO/SICCR: diagnosis and treatment of chronic constipation and obstructed defecation (part I: diagnosis). World J Gastroenterol 18:1555–1564
Bassotti G, Roberto GD, Sediari L, Morelli A (2004) Toward a definition of colonic inertia. World J Gastroenterol 10:2465–2467
Bassotti G, Villanacci V, Maurer CA et al (2006) The role of glial cells and apoptosis of enteric neurones in the neuropathology of intractable slow transit constipation. Gut 55:41–46
Bassotti G, Villanacci V, Salerni B, Maurer CA, Cathomas G (2011) Beyond hematoxylin and eosin: the importance of immunohistochemical techniques for evaluating surgically resected constipated patients. Tech Coloproctol 15:371–375
Bassotti G, Villanacci V (2006) Slow transit constipation: a functional disorder becomes an enteric neuropathy. World J Gastroenterol 12:4609–4613
Bassotti G, Villanacci V (2011) Can “functional” constipation be considered as a form of enteric neuro-gliopathy? Glia 59:345–350
Bassotti G, Carlani E, Baldoni M, Gullà N, Morozzi B, Villanacci V (2011) Painful constipation: a neglected entity? Rev Esp Enferm Dig 103:25–28
Bassotti G (2013) Understanding constipation treatment: do we need to strain to obtain better results? Expert Opin Drug Metab Toxicol 9:387–389
Conflict of interest
GB and MB have received lecturing fees for educational initiatives sponsored by Shire Pharmaceuticals.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Bassotti, G., Bellini, M. The use of prucalopride in real life for the treatment of constipation subtypes: ups and downs. Tech Coloproctol 17, 475–476 (2013). https://doi.org/10.1007/s10151-013-1026-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10151-013-1026-7