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Myths and misconceptions about the evaluation and treatment of constipation persist. Many widely prevalent misconceptions about laxatives, specifically stimulant laxatives, interfere with the effective management of constipation. Although some of these myths and misconceptions have been dispelled in recent years, there is additional room for improving the awareness and understanding of the pathophysiology of constipation, the mechanisms of action and the efficacy and safety of available therapies. An evolution in our understanding of pathophysiology and the availability of new treatments requires that primary care practitioners be better positioned to treat this common disorder that reduces patients’ quality of life and negatively impacts the healthcare system. This review defines constipation and elucidates various factors that contribute to its aetiology, including lifestyle, dietary habits, medications and underlying medical conditions. This review addresses and refutes common myths and misconceptions about constipation, such as the belief that regular bowel movements must occur daily or the use of laxatives leads to dependence. This review also highlights the importance of distinguishing between normal and abnormal bowel habits and emphasises the need for individualised management approaches to address constipation effectively. Finally, the review discusses different classes of laxatives, dispelling misconceptions about their safety, efficacy and potential for misuse, with a specific focus on stimulant laxatives. In summary, this review enhances awareness and knowledge of this prevalent disorder, provides evidence-based insights into common myths and misconceptions surrounding constipation and promotes more informed decision-making regarding constipation and the use of laxatives.

Background: In patients with irritable bowel syndrome with constipation (IBS-C), rapid, sustained relief from constipation and abdominal symptoms, such as pain, discomfort, and bloating, can improve quality of life. Objective: This post hoc analysis evaluates the time to constipation and abdominal symptom relief achieved with tenapanor. Design: Post hoc analysis of data pooled from three randomized placebo-controlled studies (phase IIb, T3MPO-1, and T3MPO-2) of tenapanor 50 mg twice daily in patients with IBS-C. Methods: The time to first response for complete spontaneous bowel movement (CSBM) frequency, abdominal pain, discomfort, bloating, and 3-item abdominal score (AS3) were assessed. The AS3 was derived as the average of the weekly scores for abdominal pain, discomfort, and bloating. Cumulative incidences of response over time were estimated using the Kaplan–Meier method. A Cox proportional hazards model was used to assess the effect of baseline and demographic characteristics on the time to first response. Results: Among 1372 patients with IBS-C (684 tenapanor; 688 placebo), median time to first CSBM response was 2 weeks, and median time to abdominal pain, discomfort, bloating, or AS3 response was 4–5 weeks in those treated with tenapanor, with 67.8%–76.7% achieving first response in CSBM frequency and abdominal symptoms by week 12. These time frames were shorter than those observed with the placebo (4 weeks for CSBM and 6–8 weeks for pain, discomfort, bloating, and AS3), of whom 59.1%–69.4% achieved the first response in CSBM and abdominal symptoms by week 12. Higher weekly response rates were observed with tenapanor than with placebo for all endpoints in each week of the 12-week treatment period. Conclusion: This novel post hoc analysis demonstrates that, compared with placebo, tenapanor reduces the time to first response in CSBM frequency and abdominal symptoms and consistently increases the weekly response rate during 12 weeks of treatment. Trial registration: NCT01923428; NCT02621892; NCT02686138.

ABSTRACTIntroductionInvestigation of an evacuation disorder is often pursued in patients with symptoms of obstructive defecation. High‐resolution anorectal manometry (HR‐ARM) is a simple, safe, and widely available test to diagnose pelvic floor dysfunction. A more costly and less accessible test is magnetic resonance defecography (MRD). This study aims to quantify the added value of MRD in diagnosing pelvic floor disorders.MethodsHR‐ARM and MRD performed in patients with a diagnosis of constipation between January 1, 2020 and May 15, 2022 at Mayo Clinic were identified using Epic Slicer Dicer. Univariate and multivariate analyses were used to compare findings on MRD in patients with and without abnormal HR‐ARM. Categorical variables were compared using the Pearson's chi‐square test, and continuous variables were compared using the two‐sample t‐test.ResultsSeventy‐six consecutive patients (81.8% female, 94.8% White, ages 19–82) who underwent both HR‐ARM and MRD were included. The majority had evidence of dyssynergia on HR‐ARM (n = 49, 64.5%). Patients with dyssynergia on HR‐ARM were significantly more likely to have prolonged balloon expulsion at both > 60 and > 30 s (p < 0.001) and incomplete gel expulsion on MRD (p < 0.001). However, they were not more likely to have a clinically significant rectocele measuring > 2 cm (p = 0.17) or evidence of rectal prolapse (p = 0.07).DiscussionAnatomic findings on MRD were similar between patients with and without evidence of dyssynergia identified by HR‐ARM. In this retrospective review, simultaneously undergoing MRD in addition to HR‐ARM does not appear to provide significant additional diagnostic information to guide therapeutic recommendations. Large prospective studies to evaluate the added value of MRD are needed.

AbstractBackgroundProkinetics are a class of pharmacological drugs designed to improve gastrointestinal (GI) motility, either regionally or across the whole gut. Each drug has its merits and drawbacks, and based on current evidence as high‐quality studies are limited, we have no clear recommendation on one class or other. However, there remains a large unmet need for both regionally selective and/or globally acting prokinetic drugs that work primarily intraluminally and are safe and without systemic side effects.PurposeHere, we describe the strengths and weaknesses of six classes of prokinetic drugs, including their pharmacokinetic properties, efficacy, safety and tolerability and potential indications.

INTRODUCTION: We investigated the efficacy and safety of virtual reality (VR) for functional dyspepsia. METHODS: Patients were randomized 2:1 between active vs sham VR. Symptoms were assessed using the Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM) over 2-week. RESULTS: Patients in the active VR group had greater numerical improvement in PAGI-SYM scores (mean difference −0.7; P < 0.001) compared with sham VR (mean difference −0.4; P = 0.032). Active VR led to significant improvements for all PAGI-SYM subscales, except lower abdominal pain, whereas sham only improved heartburn/regurgitation and nausea/vomiting. Half of the total patients reported nonserious adverse effects, although only 1 patient withdrew from the study because of adverse effects. DISCUSSION: VR is safe and results in significant symptom improvement in functional dyspepsia. Larger trials are warranted.

Summary Background MRx1234 is a live biotherapeutic product that contains a strain of Blautia hydrogenotrophica. It is in development for the treatment of irritable bowel syndrome (IBS). Aims To assess the efficacy and safety of MRx1234 in patients with IBS with predominant constipation (IBS‐C) or diarrhoea (IBS‐D) Methods We conducted a multicentre, randomised, double‐blind, placebo‐controlled, phase 2 trial. Patients aged 18–70 years in two parallel cohorts (IBS‐C; IBS‐D) were randomised (1:1) to MRx1234 or placebo for 8 weeks. The primary efficacy endpoint was overall responder rate—a composite of improved bowel habit (IBS‐C: stool frequency; IBS‐D: stool consistency) and abdominal pain intensity—for ≥50% of the treatment period in each cohort. Statistical testing was at a one‐sided 0.10 significance level. Results Of 366 randomised patients (164 IBS‐C; 202 IBS‐D), 365 received any study medication (177 MRx1234, 188 placebo). Numerically, although not statistically significantly different, more patients who received MRx1234 than placebo were overall responders in the IBS‐C (25.0% vs. 17.1%) and IBS‐D (23.4% vs. 17.8%) cohorts. Similar results were observed in the additional combined cohort analysis (24.1% vs. 17.5%; p = 0.063). For the components of the primary endpoint, significantly more patients on MRx1234 than placebo reported improvement in bowel habit in the IBS‐C, IBS‐D and combined cohorts, while improvements in abdominal pain were observed in each cohort. The safety profile of MRx1234 was similar to placebo. Conclusions MRx1234 has the potential to become a novel, safe treatment option for patients with IBS‐C or IBS‐D, and for those who have mixed symptoms or transition between subtypes. ClinicalTrials.gov #NCT03721107.

AbstractBackgroundPreclinical and clinical studies suggest that β3‐adrenergic receptor activation may be a novel target for treating abdominal pain and gastrointestinal motility dysfunction in patients with irritable bowel syndrome (IBS). This proof‐of‐concept study evaluated the efficacy and safety of the β3‐adrenergic agonist vibegron in treating IBS‐related pain.MethodsAdult women with predominant‐diarrhea IBS (IBS‐D) or with mixed diarrhea/constipation (IBS‐M), diagnosed using Rome IV criteria, were randomized 1:1 to receive once‐daily vibegron 75 mg or placebo for 12 weeks. The primary endpoint was the percentage of patients with IBS‐D considered abdominal pain intensity (API) weekly responders, defined as ≥30% reduction from baseline at week 12 in mean weekly worst abdominal pain over 24 hours using the API score. Patients completed a pain diary at baseline and at weeks 2, 4, 8, and 12. Safety was assessed by adverse events (AEs) in the overall IBS population.Key ResultsOf the 222 patients with IBS randomized (vibegron, N = 111; placebo, N = 111), 85% completed the trial. There was no significant difference in the percentage of patients with IBS‐D (vibegron, N = 66; placebo, N = 63) considered API weekly responders with vibegron vs. placebo (p = 0.8222) after 12 weeks. The incidence of AEs was comparable between treatment groups (33.3% each), with equal rates of worsening IBS symptoms (2.7% each).Conclusions and InferencesIn women with IBS‐D, vibegron was not associated with significant improvement in the percentage of API weekly responders. Vibegron was generally safe and well tolerated and, in particular, did not worsen IBS symptoms vs. placebo.

SummaryBackgroundGastroparesis has a significant negative impact on patients’ quality of life. Only one medication is approved for gastroparesis and it is associated with a significant risk of side effects.AimTo assess the willingness of patients to take risks associated with medications to treat gastroparesis symptoms.MethodsWe developed a questionnaire to assess medication risk‐taking behaviour in patients identified as having documented gastroparesis (consistent symptoms, normal upper endoscopy, delayed gastric emptying). The survey assessed demographics, symptoms, medication use, anxiety, depression and impulsivity. A standard reference gamble evaluated respondents’ willingness to take medication risks.ResultsTwo hundred seven questionnaires were mailed to patients, 103 questionnaires were completed. Seventy‐six percent were female; the mean age was 48 years; average duration of gastroparesis symptoms was 10 years. Self‐reported symptom severity was severe in 52% and moderate in 32%. Gastroparesis patients reported that they would accept a median 13.4% risk of sudden death to cure their symptoms using a hypothetical medication. Self‐reported gastroparesis symptom severity and Gastroparesis Cardinal Symptom Index scores correlated significantly with increased willingness to take risks associated with medications to treat gastroparesis, while anxiety was negatively associated.ConclusionsGastroparesis patients are willing to accept markedly high risks with a hypothetical medication to cure their symptoms. Patients with severe gastroparesis symptoms and higher Gastroparesis Cardinal Symptom Index scores were more willing to take these risks. This study, the first to quantify gastroparesis patients’ willingness to accept medication associated risks, should help clinicians through the complex maze of gastroparesis therapies and their associated risks and benefits.