Safety of Senna-Based Laxatives

A recent study  (Vilanova-Sanchez A, et al. J Pediatr Surg 2018; 53: 722-7) provides reassurance regarding the safety of senna-based laxatives in kids.

The authors performed a literature review and reviewed their personal experience (2014 to 2017) of prescribing Senna in 640 patients. In this cohort, 230 (36%) had functional constipation.

Key findings:

  • Besides abdominal cramping or diarrhea during the first weeks of administration, there were no other long-term side effects from Senna found in the pediatric literature with long-term treatment
  • At their institution, 83 (13%) patients presented minor side effects such as abdominal cramping, vomiting or diarrhea, almost half (48%) of which resolved spontaneously within two weeks.
  • “We did not see any side effects in 540 (84.3%) patients.”  The median length of treatment was 338 days and median dose was 17.5 mg.  “430 (80%) of them are currently taking Senna.”
  • 17 patients (2.2%) developed blisters during their treatment. Patients who developed blisters had higher doses 60 mg/day; 60 [12–100] vs. 17.5 [1.7–150] (p < 0.001). All of the blistering episodes were related to night-time accidents, with a long period of stool to skin contact.

In their discussion, the authors note that senna and other anthranoid glycosides are not absorbed in the small intestine.  They are maintained as prodrugs until they reach the large intestine where they are metabolized to the active form. In addition, “despite an extensive search of both the medical and lay literature we did not find any reference to long term tolerance due to treatment which we find is a frequently mentioned concern by families and clinicians”

The authors comments on the study from Nationwide Children’s Hospital website:

  • “The safety profile of senna is as good as or better than many common medications a person would be on, including over-the-counter medications routinely given to very young children, and tolerance does not appear to be a concern,” says Dr. Levitt, who is also a professor of Surgery at The Ohio State University College of Medicine. “We hope this paper will make physicians more comfortable in using senna-based laxatives, and that they will be more widely used.”
  • Senna is often more effective than polyethylene glycol. This study shows that it is safe as well.  “A physician should consider senna as the first line medication,” says Dr. Levitt.

My take: Many patients who come to pediatric gastroenterologists have not responded to polyethylene glycol.  Senna has been effective in many of these patients as part of a bowel regimen which usually includes behavior modification and diet.

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Pictures from Joshua Tree National Park

Low Adherence Rate with Polyethylene Glycol

The sentiment of wanting to get their kid off laxatives/stool softeners is frequently expressed at GI visits.  I certainly understand this.  Though, if a child is not stooling adequately when these medicines are withheld, this is usually detrimental for the child.

Given the frequency of this sentiment, it is not surprising that a recent study (IJN Koppen et al. J Pediatr 2018; 199: 132-9) reports low adherence with polyethylene glycol treatment in children with functional constipation.

In this cross-sectional survey using the Medication Adherence Report Scale (MARS-5), with scores of ≥23 indicating better adherence, the authors found that only 43 of 115 (37%) children were adherent.  The authors note that one of the determinants of adherence was treatment convenience.

The MARS-5 does not objectively measure the exact intake of medication; thus, the exact rate of adherence is unclear.  In addition, there is likely to wide variation in adherence among different populations.

My take: this study shows, at least in some populations, a low adherence with constipation therapy.  Sticking with treatment, for constipation and every other condition, usually results in better outcomes.

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If someone is not taking their medication, perhaps this cereal would help. (I am not officially endorsing this product, but think the name is funny.)

Does It Matter How Hard Your Poop Is?

A recent study (MH Vriesman et al. J Pediatr 2017; 190: 69-73) with 1835 children examined the issue of stool consistency, comparing the Bristol Stool Scale (BSS) and the Questionnaire on Pediatric Gastrontestinal Symptoms-Rome III (QPGS-RIII). Most of the patients in this study were older children, with 803 (43.7%) age 8-12 years and 1032 (56.3%) ≥13 years.

Key findings:

  • Surprisingly (to me) there only slight agreement between BSS and QPGS-RIII for assessing stool consistency (κ = .046; P=.022).
  • With the BSS, hard stools (types 1 & 2) were reported more frequently than QPGS-RIII: 18.0% vs. 7.1%.
  • Both scales reported similar levels of functional constipation, 9.3% for BSS and 8.6% for QPGS-RIII. The presence of hard stools or painful defecation is only 1 of 6 Rome criteria for the diagnosis of functional constipation.

These results indicate significant variability in how often pediatric patients considered their stools hard based on the instrument (BSS vs QPGS-RIII).  The reason why there is fairly close agreement on functional constipation is due to the fact that Rome III criteria combine the presence of hard stools and painful defecation into a single criteria and the fact that there are multiple criteria needed.  “Not all children with hard stools have painful defecation and vice versa, with only 21% of children with painful defecation reporting hard stools.”

My take: This study suggests that painful defecation is more important to ascertain than if the stools are hard. In addition, this may explain why softening the stools as a stand alone strategy is not effective in many children.

Related study: S Muddasani et al. J Pediatr 2017; 190: 74-8.  This retrospective study showed that pelvic floor physical therapy was effective in the majority of children (n=64,mean age 8.7 yrs) with fecal incontinence due to pelvic floor dyssynergia. It is notable that there were only two physical therapists involved; thus, in order to replicate these results, one would need quite capable PTs.

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Expert 2017 Opinion: Miralax is (Still) First Choice Laxative for Children

IJN Koppen et al. Journal of Pediatric Gastroenterology & Nutrition: October 2017 – Volume 65 – Issue 4 – p 361–363


 According to international guidelines, polyethylene glycol (PEG) is the laxative of first choice in the treatment of functional constipation in children, both for disimpaction and for maintenance treatment. PEG acts as an osmotic laxative and its efficacy is dose dependent. PEG is highly effective, has a good safety profile, and is well tolerated by children. Only minor adverse events have been reported. Overall the use of PEG in children has been reported to be safe, although in patients predisposed to water and electrolyte imbalances monitoring of serum electrolytes should be considered.

Because this topic is of great importance to the families that are seen by pediatric gastroenterologists (and pediatricians), I wanted to review this brief article which describes the efficacy and safety of polyethylene glycol (aka miralax).

Key Points:

  • Polyethylene glycol (PEG) is the most widely used laxative in children and adults
  • It works by interacting “with water molecules by forming hydrogen bonds, in a ratio of 100 water molecules per 1 PEG molecule, which leads to an additional increase in colonic water content.” It is minimally absorbed.
  • Studies have demonstrated that PEG is better or noninferior to all of the following: lactulose, milk of magnesia, mineral oil, and flixweed (a medicinal herb)


  • Only minor adverse events have been reported in studies.  In randomized, placebo-controlled trials, adverse events “did not occur more frequently in patients receiving PEG compared to patients receiving placebo.”
  • The main safety issue has been when it has been administered via nasogastric administration; improper placement can lead to severe pulmonary complications.  In addition, PEG should be used “cautiously in children with swallowing problems…because of risk of aspiration.”

Combatting Myths: 

  • The authors assert that there has never been reports of physical or psychological dependence.  Weaning from PEG is to prevent relapse of constipation.
  • There is no evidence to support loss of efficacy.
  • The phenomenon of “lazy bowel syndrome” in which there is worsened colonic function has not been described due to PEG; though, patients with underlying motility problems have had these problems misattributed to PEG use.
  • Despite anecdotal reports of tremors, tics, and obsessive-compulsive behavior in children taking PEG, there has been no evidence of a causal relationship.  “These events …are still under investigation, but the FDA has decided that no action is necessary.”  The authors note that the co-occurrence of neuro-behavioral problems and constipation is well-recognized in children with and without laxative use.

Clinical Pearl: Stimulant Laxatives After Repaired Anorectal Malformations:

  • “In children with constipation after repaired anorectal malformations, …stimulant laxatives (eg. senna) should be the laxative of choice.” (J Pediatr Surg 2017; 52: 84-8)

My take (borrowed from the authors): “PEG has rapidly become the treatment of first choice for children with functional constipation.”

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Diagnosis and Misdiagnosis of Constipation

A personal pet peeve is having to explain to so many parents that their child is not constipated.  The typical scenario is that their child went to the ER for abdominal pain and had an abdominal radiograph (AXR); then, the parents are informed that their child is constipated based on ‘fecal loading’ noted on the AXR.  In this scenario, it is common for the child to have the following:

  • regular bowel movements
  • lack of a rectal exam
  • lack of improvement with laxatives (though some do improve, perhaps due to the fact that symptoms often have regression to the mean)
  • often a normal AXR when interpreted by radiologist rather than ED physician (it is normal to have some stool in the colon)

So, I like to see publications that support my viewpoint that this approach is misguided. Two recent studies provide some insight into this topic:

  • SB Freedman et al. J Pediatr 2017; 186: 87-94
  • CC Ferguson et al. Pediatrics 2017; 140 (1):e20162290 (thanks to Ben Gold for this reference)

Freedman et al performed a retrospective cohort study (children <18 yrs) who were diagnosed with constipation at 23 EDs from 2004-2015. This study used the PHIS database. Key findings:

  • 185,439 of 282,225 had AXR at index ED visit
  • Revisits to ED occurred in 3.7%
  • 0.28% returned with a clinically important alternate diagnosis, most commonly appendicitis (34% in this category)
  • Children who had AXR were more likely to have a 3-day revisit with a clinically important alternate diagnosis (0.33% vs. 0.17%)

Recognizing that AXRs are “unnecessary and potentially misleading,” Ferguson et al aimed to decrease AXR utilization in low-acuity patients who were suspected of having constipation. Using quality tools, the authors performed four plan-do-study-act cycles which included holding grand rounds, sharing best practices, metrics reporting, and academic detailing. Key finding:

  • Over 12 months, we observed a significant and sustained decrease from a mean rate of 62% to a mean rate of 24% in the utilizaiton of AXRs in the ED for patients suspected of having constipation.

My take: These studies support my view that routine use of AXR in the diagnosis of constipation is a mistake and can be misleading.

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The Truth about Probiotics: Constipation Version

Families are often surprised to learn my opinion about probiotics.  The “truth” about probiotics is that they are poorly regulated/lack rigorous production standards and are mostly ineffective for many of the conditions for which they have been promoted.  Even in conditions in which there is some effectiveness (eg. antibiotic-associated diarrhea), the number of persons needed to treat for one person to benefit is fairly high.

In addition, when someone says that they are taking a probiotic, many families do not understand the idea of “strain” specific effects.  I tell families that if they see a “dog in yard” sign that they do not know if that is a poodle of a pit bull.  With probiotics, similarly you often do not know if you are getting a pit bull or a poodle.

As a consequence, I think negative studies like a recent report (K Wojtyniak et al. J Pediatr 2017; 184: 101-05) are helpful. In this study, the authors examined the effectiveness of Lactobacillus casei rhamnosus Lcr35 (Lcr35) in the management of constipation.

This randomized, double-blind, placebo-controlled trial was conducted in 94 children <5 years of age. Dose: 8 x10 to the 8th CFU twice daily x 4 weeks.

Key findings:

  • “Lcr35 as a sole treatment was not more effective than placebo in the management of functional constipation.” In fact, the placebo group had a greater increase in bowel movement frequency than the treatment group.
  • Both groups had improvement -more than half in each group (total 52 of 81 who completed study) had reached endpoint of 3 or more BMs/week without soiling.

My take: Probiotics often are ineffective.  This study showed that Lcr35 was NOT helpful for pediatric constipation.

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Claude Monet, La Rue Montorgueil



FDA Approves Plecanatide (Trulance) for Adults with Idiopathic Constipation

Here’s the link: FDA approves Trulance for Chronic Idiopathic Constipation (Jan 19.2017).  Plecanatide is a guanylate cyclase-C agonist.

An excerpt:

Trulance, taken orally once daily, works locally in the upper GI tract to stimulate secretion of intestinal fluid and support regular bowel function.

The safety and efficacy of Trulance were established in two 12-week, placebo-controlled trials including 1,775 adult participants. Participants were randomly assigned to receive a placebo or Trulance, once daily. Participants in the trials were required to have been diagnosed with constipation at least six months prior to the study onset and to have less than three defecations per week in the previous three months, as well as other symptoms associated with constipation. Participants receiving Trulance were more likely to experience improvement in the frequency of complete spontaneous bowel movements than those receiving placebo, and also had improvements in stool frequency and consistency and straining.

Trulance should not be used in children less than six years of age due to the risk of serious dehydration… The safety and effectiveness of Trulance have not been established in patients less than 18 years of age.

The most common and serious side effects of Trulance was diarrhea.

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