There has been an increase in the number of over-the-counter (OTC) therapies for patients with chronic constipation, with improvements in the quality of evidence supporting their efficacy, according to study results published in The American Journal of Gastroenterology. Some therapies such as polyethylene glycol and senna have good evidence for treatment of constipation, while the use of psyllium, fruits, and bisacodyl have moderate evidence.
Chronic constipation is a common condition and nearly 40% of people with constipation self-treat with OTC laxatives; however, the efficacy and safety of these therapies is still not clear. To address this knowledge gap, a pair of investigators conducted an evidence-based systematic review of OTC therapies by reviewing data published throughout the last 15 years. They aimed to update the classification of therapies and to recommend treatments based on the strength and levels of supporting evidence.
Of the 110 randomized clinical trials identified, 41 studies were included in the analysis. To measure the strength of evidence and grade of recommendations, the researchers used the current United States Preventive Services Task Force criteria, which categorized levels of evidence as good (level 1), fair (level 2), or poor (level 3). Recommendations were categorized as A (good evidence in support), B (moderate evidence in support), C (poor evidence in support), D (moderate evidence against), or I (insufficient evidence). The OTC options were categorized into 1 of 8 groups: osmotic laxatives, fiber laxatives, stimulant laxatives, magnesium-based laxatives, fruit-based laxatives, foods with prebiotics, surfactants, and miscellaneous agents.
A total of 9 studies including polyethylene glycol were analyzed and no other osmotic agents met the current inclusion criteria. Polyethylene glycol is effective with minimal side effects and has superior response rates to psyllium and prescription agents. It has level 1 evidence and grade A recommendation. Data supported the use of polyethylene glycol as a first-line agent to treat chronic constipation.
Fiber products can be classified based on solubility, viscosity, and fermentability. Insoluble fibers include cellulose, lignin, and oligosaccharides, while fermentable fibers include gums, inulin, oligosaccharides, and wheat dextrin that is digested by bacteria in the gut. The researchers noted that soluble fibers were safe and well tolerated in the observed studies.
“Overall, considering the differences in products tested, dosages used, and variability in study design, the current data suggest that both soluble fiber, psyllium, and mixed fiber (SupraFiber) have modest efficacy for treating constipation,” the authors noted.
Psyllium and mixed fiber both had level 2 evidence and grade B recommendations, while polydextrose and inulin both had level 1 evidence and grade I recommendations.
Stimulant agents were subdivided into diphenylmethane derivatives (such as bisacodyl and sodium picosulfate) and plant-based anthraquinones (such as senna, aloe, and cascara). Of these, senna was most favorable with level 1 evidence and grade A recommendation. Bisacodyl and sodium picosulfate both had level 1 evidence and grade B recommendation.
“Although magnesium citrate is a stronger formulation with more characteristically osmotic properties, other agents including magnesium hydroxide, magnesium gluconate, and magnesium oxide or magnesium enriched water act as more gentle saline laxatives,” the authors noted.
Studies reported that magnesium-containing mineral water preparations or magnesium oxide were well tolerated and showed improvements in constipation. The investigators noted that magnesium-containing agents had level 1 evidence and grade B recommendation.
Fruit-based laxatives were found to be very well tolerated with minimal or no adverse events reported, according to the observed studies; however, because the studies had small sample sizes, more trials may be required to confirm their efficacy.
Kiwi-based laxatives had level 1 evidence with grade B recommendations, while mango-based, ficus-based, and prune-based laxatives all had level 2 evidence with grade B recommendations.
Foods With Prebiotics
Of the 2 studies including prebiotics, 1 analysis found that yogurt with galacto-oligosaccharides, prunes, and linseed oil may significantly increase stool frequency and easier defecation, while the other analysis evaluated outcomes in the consumption of rye bread with or without Lactobacillus GG-containing yogurt. Yogurt with galacto-oligosaccharides, prunes, and linseed oil was found to have level 2 evidence and grade B recommendation. Rye bread with yogurt had level 3 evidence and grade C recommendation.
Although docusate, an anionic surfactant, is commonly used as an OTC agent for constipation, data on its efficacy have been inconsistent. No additional studies since 2004 met the inclusion criteria for the present investigation. Therefore, surfactants were deemed to have level 3 evidence and grade I recommendation.
In studies evaluating constipation in patients with chronic kidney disease (CKD) and other studies reviewing miscellaneous agents the investigators found that polydextrose had level 2 evidence and grade B recommendation for patients with CKD; flaxseed oil had level 2 evidence and grade C recommendation for patients with CKD; and fructo-oligosaccharide had level 3 evidence with grade I recommendation in patients with CKD.
“Overall, the OTC products analyzed in this review seemed to be safe and well tolerated, with no reports of serious adverse events, although some studies failed to report any adverse events,” the researchers noted.
“[Polyethylene glycol] and senna are the only OTC laxatives with level  evidence and grade A recommendations for the treatment of constipation, although [polyethylene glycol] is the only one supported by both short- and long-term studies,” the investigators added.
“[T]here is a clear need for more rigorous, high-quality studies using standardized endpoints,” they wrote.
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Rao SSC, Brenner DM. Efficacy and safety of over-the-counter therapies for chronic constipation: an updated systematic review. Am J Gastroenterol. 2021;116(6):1156-1181. doi:10.14309/ajg.0000000000001222
This article originally appeared on Gastroenterology Advisor