Data on the use of antispasmodics available in North America for the treatment of chronic abdominal pain in patients with disorders of gut-brain interaction (DGBI) vary dramatically in safety and efficacy, according to a literature review published in The American Journal of Gastroenterology. Overall, data supporting the use of antispasmodics in this patient population are lacking.
In the United States, abdominal pain is considered the most common gastrointestinal (GI) symptom leading to an office-based outpatient or emergency department visit. Functional GI disorders are now formally described as DGBI, and are considered the underlying cause of abdominal pain in a significant proportion of patients. DGBI include irritable bowel syndrome (IBS), functional dyspepsia (FD), and centrally mediated abdominal pain syndrome (CAPS). The symptoms of abdominal pain in the aforementioned disorders are often treated with antispasmodics.
In this review, researchers aimed to explore the safety and efficacy of individual antispasmodics available in North America (alverine, dicyclomine, hyoscine, hyoscyamine, mebeverine, otilonium, pinaverium, and trimebutine) for the treatment of chronic abdominal pain in patients with DGIB.
PubMed and Embase were electronically searched through December 2020 (start date, 1963 for PubMed and 1947 for Embase) for results of randomized, placebo-controlled, parallel, or crossover studies on antispasmodics conducted in adults with abdominal pain due to IBS, dyspepsia/FD, and CAPS. The search included antispasmodics currently available in North America (United States, Canada, and Mexico). The Cochrane Collaboration’s “Risk of Bias” tool was utilized to evaluate the risk of bias in articles included in the review.
The PubMed and Embase database searches identified a total of 492 publications. In addition, 11 references were identified from reference lists in relevant review articles and the Cochrane Central Register for Controlled Trials. In total, 26 studies, including 23 focusing on IBS, 1 on FD, and 2 on recurrent abdominal pain with cramping (APC), were included in the review. The investigators noted that no studies assessing antispasmodics in patients with CAPS were identified.
Antispasmodics for IBS
According to the results of 2 randomized, placebo-controlled studies, dicyclomine improved symptoms of IBS relative to placebo. A comparison between both studies revealed conflicting information regarding adverse events (AEs). Efficacy data were generally favorable. However, these studies used different doses of dicyclomine, had short treatment duration (10 days-2 weeks), and 1 study had a high risk of allocation bias.
In 3 studies, hyoscine taken for a duration of 4 weeks to 3 months was found to be more effective compared with placebo for improving IBS symptoms. In 2 of these studies, AEs were not adequately reported. All 3 studies reported favorable efficacy, but they differed in terms of treatment duration and definitions of IBS, and separate evaluations of abdominal pain in 2 studies were limited.
In 1 small crossover study, hyoscyamine 0.2 mg 3 times per day over a 2-week period (dose increased if IBS symptoms persisted) improved IBS symptoms from baseline. However, this improvement was not considered significant compared with placebo.
In 2 randomized, placebo-controlled trials, the efficacy of mebeverine was evaluated. In the first study, 16 weeks of treatment with mebeverine 100 mg 4 times per day was less effective in patients with IBS compared with placebo for improving symptoms of abdominal pain, flatulence, and irregular bowel habits. No clinically relevant AEs were reported in either treatment group. In a second study, 6 week treatment with mebeverine 135 mg 3 times per day with or without the use of a self-management website had no greater efficacy compared with placebo for improving IBS symptoms. AEs were not reported in this study.
In 2 randomized, placebo-controlled studies, the safety and efficacy of alverine were examined. In the first study, a comparable proportion of patients receiving alverine 120 mg 3 times per day or placebo for 12 weeks experienced improvements from baseline in the intensity and frequency of abdominal pain, bloating, and well-being at week 12. The differences in both groups did not reach statistical significance. In the second study, alverine 60 mg/simethicone 300 mg 3 times per day was significantly more effective compared with placebo for improving abdominal pain among patients with IBS (P =.047). The safety profiles of alverine/simethicone were noted to be generally comparable with placebo, although the study potentially precluded patients with more severe symptoms.
In 4 randomized, controlled studies, the efficacy and safety of otilonium were evaluated. In 3 studies, otilonium 40 mg 3 times per day reduced abdominal pain frequency when compared with placebo over weeks 3 to 4 and at week 15. In 1 study, otilonium was associated with mild nausea. No AEs were reported with placebo. In another study, prostate disturbance and dizziness were reported with otilonium, and skin rash with placebo. These AEs ultimately led to study withdrawal. In a dose-ranging study, otilonium 20, 40, and 80 mg 3 times per day reduced the intensity and frequency of abdominal pain and bloating from baseline to 4 weeks. The investigators observed no differences between otilonium and placebo after treatment.
In 5 randomized, placebo-controlled IBS studies, the safety and efficacy of pinaverium were reported. In 3 small, single-center studies published in 1995 or earlier, pinaverium 50 mg 3 times per day improved abdominal pain in patients with IBS. Two larger, multicenter, double-blind, placebo-controlled studies assessed the safety and efficacy of pinaverium in patients with IBS diagnosed per Rome III criteria. Patients experiencing IBS with diarrhea (IBS-D) receiving pinaverium 50 mg 3 times per day experienced significant improvements in composite abdominal pain and stool consistency response compared with placebo at weeks 2 and 4 (P >.05 and P <.001, respectively). The most common AEs among study participants were nausea, dizziness, abdominal discomfort, and hypertension.
Across 4 small studies of trimebutine 100 or 200 mg 3 times per day administered for 2 weeks to 6 months, improvements in abdominal pain were not consistently observed. In all 4 studies, safety data were inconsistently presented.
Antispasmodics for Abdominal Pain in Other Functional GI Disorders
Hyoscine for Recurrent Abdominal Pain
In 2 multicenter studies evaluating the safety and efficacy of hyoscine for the treatment of recurrent APC not linked to altered bowel habits, after 3 weeks of treatment, a significant reduction from baseline in abdominal pain intensity with hyoscine 10 mg 3 times per day compared with placebo was reported (P <.0001). Abdominal pain frequency also significantly decreased with hyoscine compared with placebo (P <.0001). During a 4-week period, on-demand hyoscine treatment with 20 to 100 mg over 4 hours reduced abdominal pain intensity compared with placebo during the first APC episode (P =.02), but not during a second, separate APC episode. Hyoscine was noted to be well tolerated in both studies.
Trimebutine for Patients With FD
According to the results of a small crossover study, trimebutine 200 mg 3 times per day in patients with FD reported no significant improvement in overall dyspeptic symptoms (including abdominal pain) compared with placebo after 4 weeks of treatment. During trimebutine treatment, the reported AEs were fatigue and transient penile rash. During placebo treatment, no AEs were reported.
The researchers determined that the antispasmodics examined in the review varied dramatically in safety and efficacy.
“This highlights the need to use other therapies to treat chronic abdominal pain (e.g., neuromodulators and cognitive behavioral therapy) and to develop agents to treat this debilitating symptom,” the study authors wrote.
Disclosure: Both study authors declared affiliations with the industry. Pease see the original reference for a full list of authors’ disclosures.
Disclosure: This research was supported by multiple sources. Please see the original reference for a full list of disclosures.
Brenner DM, Lacy BE. Antispasmodics for chronic abdominal pain: analysis of North American treatment options. Am J Gastroenterol. 2021;116(8):1587-1600. doi: 10.14309/ajg.0000000000001266