Constipation in children - Emerging treatments

Prucalopride

Prucalopride is a 5-HT4 receptor agonist approved for the treatment of constipation in adults.[53] 5-HT4 is a serotonin receptor with a role in gastrointestinal motility. Enhancing the activity of 5-HT4 with receptor agonists has been shown to improve functional constipation.[54] The results of a multicentre, randomised, placebo-controlled, double-blind phase III trial to evaluate the efficacy and safety of prucalopride in children aged 6 months to 18 years with functional constipation found that although the drug was generally well tolerated, it was no more effective than placebo.[55] Other trials of prucalopride in children and adolescents remain ongoing.

Lubiprostone

Lubiprostone is an oral chloride channel activator that enhances gastrointestinal fluid secretion, subsequently softening stools and facilitating bowel movements. It has been approved for use in adult patients in the US since 2006. Clinical trials in children have shown that lubiprostone has a similar safety profile to that observed in adults, but efficacy results have been mixed.[56][57][58] In one open-label study that enrolled 127 children aged ≤17 years, lubiprostone significantly improved spontaneous bowel movements (SBM) from baseline to week 4.[57] However, in a phase 3 randomised controlled trial, lubiprostone failed to significantly improve SBM compared to placebo from baseline to week 12.[58] Lubiprostone continues to be used off-label in children in some centres.

Botulinum toxin

Injection of botulinum toxin type A into the intra-anal sphincter shows some promising response, and several groups are using this therapy, especially when anal fissures are present, or a hypertonic or non-normally relaxing internal anal sphincter is present.[59][60] Limitations include cost, requirement for general anaesthetic, and transient efficacy.[53]

Probiotics

It is hypothesised that probiotics favourably alter the gut microbiome and promote normal gut physiology in a way that leads to improvement in constipation. However, their use remains controversial.[30][53] One Cochrane review investigated the efficacy and safety of probiotics for the treatment of chronic functional constipation in children. The authors of the review concluded that there was a lack of evidence in the 14 evaluated studies to routinely recommend probiotics for this purpose.[61]

Sacral nerve stimulation (SNS)

SNS involves implantation of an electrode in the sacral foramen in order to apply low-amplitude electrical stimulation to the sacral nerve.[53] Studies in children and adolescents have yielded mixed results, with some suggesting sustained results up to 2 years and other failing to show clinical benefit.[53][62][63] A non-invasive form of SNS has been piloted in a small group of 17 children (mean age 6.5 years) with promising results.[64] It is hoped that non-invasive SNS will avoid problems associated with electrode displacement as children grow.[64]