Introduction Chronic constipation is a global public health problem that affects the lives of children and caregivers. A subset of children with constipation do not respond to standard medical management and are considered as having intractable constipation. Management of these children is a challenging problem for practicing pediatric gastroenterologists.

Aim We set out to evaluate the efficacy and safety treatment options of intractable constipation in children.

Subjects and Methods We searched Pubmed, MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, ClincalTrials.gov, and the World Health Organization International Clinical Trial Registry Platform (ICTRP) froth their inception to July 2021. Two authors independently identified relevant papers, extracted data, and evaluated risk of bias tool. The Rome III committee’s primary and secondary outcomes were used to evaluate the efficacy of interventions. We used the GRADE criteria to assess the overall certainty of the evidence.

Results Eight randomised controlled trials on 1197 children from 6 months to 18 years were included in the review. All studies compared different interventions. The intervention comparisons were: botulinum toxin injection to exclusive therapy with stool softeners; lubiprostone to placebo; rectal enemas and conventional therapy to conventional therapy only; erythromycin to placebo; : botulinum toxin injection to myectomy of the internal anal sphincter; personalised dietary advice to physician dietary advice; prucalopride to placebo; and transcutaneous electrical stimulation to sham therapy. No conclusions could be reached on any of our outcomes due to the very low certainty of the evidence resulting from low participant numbers, risk of bias and high heterogeneity between included participants and interventions.

Conclusion No conclusions can be reached on the efficacy and safety of any of the above therapies due to limited numbers of participants per comparison, high heterogeneity between studies and interventions, capricious reporting of data, and issues with risk of bias. Therefore, there is no evidence to support using any of these treatments in clinical practice at present. Further well-designed, appropriately powered, randomized controlled trials are essential to generate more robust evidence-based clinical interventions for the management of intractable constipation. A lack of consensus definition on intractable constipation is an issue that needs to be resolved in the next iteration of the ROME criteria, which will allow for more homogenous future RCTs.